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    Basic research
    Protective effect of pituitary adenylate cyclase-activating polypeptide 38 on acute radiation-induced myocardial injury
    Huan LI, Pei-qiang YI, Jun SU, Pei-zhan CHEN, Cheng XU, Lu CAO, Jia-yi CHEN, Min LI
    2021, 41 (2):  129-133. 
    doi: 10.3969/j.issn.1674-8115.2021.02.001

    Abstract ( 514 )   HTML ( 14 )   PDF (1942KB) ( 262 )  
    Objective

    ·To explore the effect of pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) on radiosensitivity of myocardial cells and its potential protective effect on acute radiation-induced myocardial injury.

    Methods

    ·The radiation-related cardiac injury models were established by using 6 MV X-ray with H9C2 cardiomyocytes and male C57BL/6J mice which were pre-treated with different doses of PACAP38 prior to radiation exposure. H9C2 cells were treated with 10-9 and 10-7 mol/L PACAP38 2 h before irradiation. 10 μg of 0.1 μg/μL PACAP38 was administered to C57BL/6J mice intraperitoneally at 2 h before irradiation and additional doses were given at 24 h and 48 h after irradiation. In vivo and in vitro myocardial radiation injury models were divided into control group, PACAP38 group, irradiation group (IR) and PACAP38+IR group. The specific irradiation doses in vitro were 2, 4, 8 and 12 Gy. The specific irradiation dose in vivo were 14 Gy, one fraction irradiation. CCK-8 and clonogenesis assays were used to examine cell viability and radiosensitivity, respectively. Hematoxylin and eosin staining was used to evaluate the pathological changes of myocardial tissue in mice after one-month irradiation.

    Results

    ·The cell viability of H9C2 cardiomyocytes pretreated with PACAP38 was significantly higher than that of irradiation (12 Gy) alone [10-7 mol/L PACAP38+IR group vs IR group, (98.63±2.70)% vs (83.67±0.78)%, P=0.000]. The survival fraction at 2 Gy increased from 0.53 to 0.63 and 0.70 after 10-9 and 10-7 mol/L PACAP38 pretreatment, and the sensitivity enhancement ratio of 10-9 and 10-7 mol/L PACAP38 pretreatment groups were 0.95 and 0.91, respectively. In vivo studies showed that PACAP38 could significantly alleviate the pathological damage of myocardial tissue after irradiation (14 Gy), including cardiomyocyte degeneration, eosinophilic enhancement, cytoplasmic vacuolation, nuclear pyknosis and myocardial fiber distortion.

    Conclusion

    ·PACAP38 can significantly reduce the radiosensitivity of myocardial cells and has a certain protective effect on acute radiation-induced myocardial injury.

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    Establishment of continuous glucose monitoring in mice and multiscale entropy analysis of glucose time series
    Cheng LI, Ming-liang ZHANG, Ling-wen YING, Jiao-rong SU, Rui TAO, Xia YU, Yu-qian BAO, Jian ZHOU
    2021, 41 (2):  134-139. 
    doi: 10.3969/j.issn.1674-8115.2021.02.002

    Abstract ( 779 )   HTML ( 15 )   PDF (2592KB) ( 418 )  

    Objective·To establish continuous glucose monitoring (CGM) in mice and implement multiscale entropy (MSE) analysis of glucose time series. Methods·Diet-induced obesity (DIO) mice (n=3) and control mice (n=3) were selected as the research objects. The blood glucose and body temperature data of the two groups were collected by using the implantable glucose telemetry system. The data of 10?14 days after operation were analyzed, and the recording time of the system was counted. Using MATLAB R2019b software, MSE analysis was performed on glucose time series of the two groups from 11 to 17 days after operation, and the corresponding entropy value on each time scale was calculated. Results·The CGM technology based on the implantable glucose telemetry system in mice was successfully established. The average recording time of the 6 mice was (27.3±9.3) d, and 232 887 blood glucose values were obtained. The mean blood glucose level of the DIO mice was (7.04±0.71) mmol/L and the mean body temperature was (33.34±0.18) ℃. Compared with that of the control mice, the glucose time series complexity of the DIO mice was lower, and the difference between the two groups was not statistically significant. Conclusion·The CGM technology in mice is successfully established. MSE analysis shows that the complexity of glucose time series in the DIO mice decreases, which may be one of the manifestations of abnormal glucose metabolism in the early stage.

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    Fabrication and characterization of matrix metalloproteinase-responsive G4 PAMAM-IBU/GelMA hydrogel
    Chuan-dong CAI, Fei WANG, Wen-guo CUI, Cun-yi FAN, Shen LIU
    2021, 41 (2):  140-146. 
    doi: 10.3969/j.issn.1674-8115.2021.02.003

    Abstract ( 792 )   HTML ( 23 )   PDF (2933KB) ( 506 )  
    Objective

    ·To fabricate matrix metalloproteinase (MMP)-responsive gelatin (Gel) hydrogel loaded with generation 4 polyamindoamine (G4 PAMAM)/ibuprofen (IBU) polyplexes (G4 PAMAM-IBU), and investigate its characteristics in vitro.

    Methods

    ·The G4 PAMAM was mixed with IBU powder to form G4 PAMAM-IBU polyplexes under ultrasound vortex. The concentration of IBU in the saturated G4 PAMAM-IBU solution was determined by ultraviolet spectrophotometer. The solubilization ability of G4 PAMAM for IBU and the release of IBU in G4 PAMAM-IBU were assessed. And the ability of IBU and G4 PAMAM-IBU to inhibit the proliferation of rat fibroblasts was verified by CCK-8 assay. Meanwhile, to achieve the on-demand release of G4 PAMAM-IBU, Gel and methacrylic anhydride were used to synthesize methacrylate modified gelatin (GelMA) through an addition reaction, MMP-responsive hydrogel was formed under 365 nm light, and the G4 PAMAM-IBU polyplexes were embedded in the hydrogel. The microscopic morphology of the hydrogel was observed by scanning electron microscope (SEM) and the amount of released IBU was measured by ultraviolet spectrophotometer. Then, drug-loaded GelMA hydrogel was co-cultured with fibroblasts, and the effect of hydrogel on proliferation of fibroblasts was evaluated by CCK-8 assay and live/dead cell staining. The differences in the quantitative data among the groups were analyzed by using one-way ANOVA.

    Results

    ·G4 PAMAM-IBU was formed successfully, the solubility of IBU in water increased obviously, and G4 PAMAM-IBU could gradually dissociate within 12 h and thereby release IBU as well. Compared with the blank control group, the concentration of IBU alone needed to reach 300 μg/mL to inhibit the proliferation of fibroblasts (P=0.023), while the concentration of IBU in G4 PAMAM-IBU was 100 μg/mL to significantly inhibit the proliferation of fibroblasts (P=0.000). The SEM images and released IBU detection results showed that the internal porosity of the prepared G4 PAMAM-IBU/GelMA hydrogel increased and the release of the drug accelerated. Besides, the in vitro results showed that compared with the IBU/GelMA hydrogel, there were less live cells and more dead cells in the G4 PAMAM-IBU/GelMA hydrogel-treated fibroblasts. G4 PAMAM-IBU/GelMA hydrogel had a greater proliferation inhibitory effect than the IBU/GelMA hydrogel. And the addition of MMP further enhanced the inhibitory effect on fibroblasts.

    Conclusion

    ·G4 PAMAM can significantly increase the solubility of IBU and improve its drug effect; the G4 PAMAM-IBU/GelMA hydrogel has a sustained drug release behavior responding to MMP and can inhibit the proliferation of fibroblasts sustainably.

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    Effects of exosomes derived from human umbilical vein endothelial cells on apoptosis of pre-chondrogenic cells stimulated by inflammatory factors
    Run-ze YANG, Wen-ning XU, Huo-liang ZHENG, Sheng-dan JIANG
    2021, 41 (2):  147-153. 
    doi: 10.3969/j.issn.1674-8115.2021.02.004

    Abstract ( 658 )   HTML ( 28 )   PDF (3474KB) ( 314 )  
    Objective

    ·To investigate the effect of exosomes derived from umbilical vein endothelial cells (HUVECs) on apoptosis of murine pre-chondrogenic cell line ATDC5 cells under inflammatory stimulation.

    Methods

    ·The exosomes derived from HUVECs were isolated by using an exosome isolation kit. Western blotting was used to detect the exosome marker proteins, including tumor susceptibility gene 101 (Tsg101), cluster differentiation 9 (CD9) and apoptosis linked gene-2-interacting protein X (Alix). The morphology of exosomes was observed by transmission electron microscope, and the size of exosomes was identified by particle size detection. Fluorescence microscope was used to observe the ATDC5 cell uptake of exosomes and the production of reactive oxygen species (ROS). TUNEL staining and flow cytometry were used to examine the effect of exosomes on ATDC5 cell apoptosis stimulated by interleukin-1β (IL-1β). Western blotting was used to detect the effect of exosomes on the expression levels of ATDC5 apoptosis-related proteins such as B-cell lymphoma/leukemia 2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved caspase-3 (c-caspase-3) and anti-oxidative stress-related proteins such as nuclear factor E2 related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase-like protein 1 (NQO-1) under IL-1β stimulation.

    Results

    ·Under the transmission electron microscope, the HUVEC-derived exosomes were oval, hollow, double-layered, and positively expressed exosome markers CD9, Alix and Tsg101. Compared with the ATDC5 cells stimulated by IL-1β, ATDC5 cells stimulated by IL-1β incubated with exosomes had higher level of ROS (P=0.000) and higher apoptosis rate (P=0.000). The expression of Bax, c-caspase-3 and Keap-1 increased, and the expression of Bcl-2, Nrf-2, HO-1 and NQO-1 decreased in ATDC5 cells exposed to IL-1β and exosomes compared to ATDC5 cells only exposed to IL-1β.

    Conclusion

    ·HUVEC-derived exosomes may promote ATDC5 cells apoptosis under the stimulation of IL-1β by inhibiting the ability of ATDC5 cell to resist oxidative stress.

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    ATP-sensitive potassium channel negatively regulates hippocampal long-term potentiation maintenance
    Xiao-lin ZHANG, Xiao-yun ZHANG, Gui-qin HE, Yue KONG, Zi-kai ZHOU
    2021, 41 (2):  154-158. 
    doi: 10.3969/j.issn.1674-8115.2021.02.005

    Abstract ( 555 )   HTML ( 9 )   PDF (1563KB) ( 351 )  
    Objective

    ·To investigate the regulatory roles of ATP-sensitive potassium channel (KATP) in the induction and maintenance stages of long-term potentiation (LTP), which is an experimental model for studies of synaptic plasticity and memory.

    Methods

    ·Acute brain slices were prepared from male C57BL/6 mice at 5?6 weeks of age. Electrophysiological recording of the field excitatory postsynaptic potentials was performed at the hippocampal Schaffer collateral-commissural pathway. KATP opener cromakalim was used to activate KATP at basal level, induction and maintenance stages of LTP. Oxygen-glucose deprivation (OGD) was used to induce hypoxia and pathological opening of KATP at the maintenance stage of LTP. Tolbutamide (TOL) was used to block KATP before OGD treatment.

    Results

    ·KATP opening showed no effects on basal synaptic transmission and the induction of LTP, but largely decreased the magnitude of LTP at maintenance stage. OGD rapidly impaired LTP maintenance, which was significantly prevented by TOL pre-treatment.

    Conclusion

    ·KATP negatively regulates hippocampal LTP maintenance in both physiological and pathological conditions.

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    Establishment and validation of prognostic prediction model of colorectal cancer based on single-cell RNA sequencing
    Yan-ru MA, Lin-hua JI, Tian-ying TONG, Yu-qing YAN, Chao-qin SHEN, Xin-yu ZHANG, Ying-ying CAO, Jie HONG, Hao-yan CHEN
    2021, 41 (2):  159-165. 
    doi: 10.3969/j.issn.1674-8115.2021.02.006

    Abstract ( 1044 )   HTML ( 41 )   PDF (3176KB) ( 637 )  
    Objective

    ·To establish a model for predicting the prognosis in patients with colorectal cancer (CRC) using single cell RNA sequencing (scRNA-seq).

    Methods

    ·scRNA-seq data of patients with CRC from Gene Expression Omnibus (GEO) database was used to filter out candidate genes, which were related to metastatic CRC. The least absolute shrinkage and selection operator (LASSO) regression, Logistic regression and Kaplan-Meier analysis were used to select and evaluate the significance of the hub gene filtered out in The Cancer Genome Atlas (TCGA) database, and to develop the prognostic prediction model of CRC. Decision curve analysis and receiver operating characteristic (ROC) curve were used to assess the clinical use of the prediction model.

    Results

    ·Thirty candidate genes were filtered out from the scRNA-seq data which was downloaded in GEO database, and then 9 hub genes were selected by LASSO regression in the TCGA database. The hub-gene expression was scored for each patient. The scores had significant difference between the groups with and without recurrence both in the training set and the validation set (P<0.05). In addition, Logistic regression analysis was carried out to incorporate the two independent clinical variables of primary tumor grade (T stage) and metastasis status (M stage) into the score-clinical variable integration model. Area under curve of the ROC curve in the training set and validation set were 0.775 and 0.705, respectively.

    Conclusion

    ·A relatively stable model for predicting prognosis in CRC was constructed based on the results of scRNA-seq, which has certain guiding significance for treatment decision and prognostic prediction.

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    Clinical research
    Detection of vessel density changes in eyes of patients with diabetic retinopathy and diabetic macular edema using optical coherence tomography angiography
    Han-ying WANG, Yan JIANG, Ching-yi WANG, Xin SHI, Tian NIU, Xin-dan XING, Yin-chen SHEN, Chong CHEN, Kun LIU
    2021, 41 (2):  166-172. 
    doi: 10.3969/j.issn.1674-8115.2021.02.007

    Abstract ( 580 )   PDF (2308KB) ( 444 )  
    Objective

    ·To observe the features of diabetic retinopathy (DR) at different stages, which is accompanied/not accompanied by diabetic macular edema (DME), using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA), and to determine related risk factors and potential OCTA imaging biomarkers of DR progression.

    Methods

    ·Ninety DR patients from Shanghai General Hospital, Shanghai Jiao Tong University were divided into four groups according to early treatment of diabetic retinopathy study (ETDRS) grading standard (mild, moderate, severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy groups), or two groups according to the presence of DME or not. OCTA metrics, including superficial vessel density, deep vessel density and foveal avascular zone area were compared. Logistic regression was used to exclude confounding factors. Imaging changes related to DR severity and DME occurrence, as well as other factors including gender, age, history of underlying diseases, use of antihypertensive drugs and blood indicators were searched.

    Results

    ·Lower age of the onset of diabetes (P=0.042, 95%CI -0.057--0.001) and lower deep vessel density (P=0.040, 95%CI -0.066--0.002) were significantly associated with DR progression. The absence of hyperlipidemia was a protective factor for the progression of DR disease (P=0.027, 95%CI -3.001--0.176). The incidence of DME increased with the severity of DR (P=0.004), and the occurrence of disorganization of retinal inner layers was significantly related to DME (P=0.000). No alteration in vessel density was observed between patients with DME and those without DME.

    Conclusion

    ·The progression of DR may be closely related to the vessel density of deep retinal vessels, which may become an imaging biomarker to predict the development of DR.

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    Effect of microvascular obstruction on left ventricle function and prognosis in patients with ST-segment elevation myocardial infarction
    Pei-kun HU, Jie HE, Lian-ming WU, Heng GE, Jian-rong XU, Jun PU
    2021, 41 (2):  173-179. 
    doi: 10.3969/j.issn.1674-8115.2021.02.008

    Abstract ( 626 )   HTML ( 6 )   PDF (1824KB) ( 300 )  
    Objective

    ·To investigate the effect of microvascular obstruction (MVO) on left ventricle function and prognosis in patients with ST-segment elevation myocardial infarction (STEMI) by using cardiac magnetic resonance (CMR) technique.

    Methods

    ·A total of 124 patients with STEMI in the Department of Cardiology of Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2017 were enrolled. The percentage of myocardial infarction size, the percentage of myocardial MVO size and left ventricle function after reperfusion were evaluated by CMR technique. According to the percentage of myocardial MVO size, the patients were divided into MVO (+) group and MVO (-) group. The baseline characteristics, blood biochemical indexes and CMR indexes of the two groups were compared. The MVO (+) group was further divided into 4 subgroups according to the quartiles of the percentage of myocardial infarction size. Pearson correlation analysis was used to explore the correlation between the percentage of myocardial MVO size and left ventricular ejection fractions (LVEF) in each subgroup. The incidence of adverse events within 30 days was observed. Receiver operating characteristic curve (ROC curve) was used to analyze the predictive value of the percentage of myocardial MVO size for adverse events.

    Results

    ·The white blood cell count, creatine phosphokinase, creatine kinase MB, cardiac troponin I and total cholesterol in the MVO (+) group were significantly higher than those in the MVO (-) group (all P<0.05), while baseline characteristics showed no significant difference. LVEF in the MVO (+) group was lower than that in the MVO (-) group (P=0.000). Pearson correlation analysis showed that the percentage of myocardial MVO size was negatively correlated with LVEF (all P<0.05). ROC curve showed that the area under the curve of the percentage of myocardial MVO size in the prediction of adverse events within 30 days was 0.889 (95%CI 0.823?0.975), and the sensitivity and specificity of the percentage of myocardial MVO size were more higher than that of the percentage of myocardial infarction size.

    Conclusion

    ·The left ventricle function and prognosis in STEMI patients with MVO are worse, suggesting that more attention should be paid to the clinical intervention for such patients.

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    Association between body mass index and myocardial involvements in patients with systemic lupus erythematosus
    Ze-hao FENG, Ye-zi CHAI, Xuan SU, Bao-hang-xing SUN, Qi-ming LIU, Meng JIANG, Jun PU
    2021, 41 (2):  180-186. 
    doi: 10.3969/j.issn.1674-8115.2021.02.009

    Abstract ( 529 )   HTML ( 4 )   PDF (1520KB) ( 253 )  
    Objective

    ·To explore the association between body mass index (BMI) and myocardial involvement in patients with systemic lupus erythematosus (SLE).

    Methods

    ·Fifty-four healthy participants and sixty-one patients with SLE who were admitted to the Department of Cardiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine were prospectively recruited from July 2014 to November 2016 and then underwent cardiac magnetic resonance (CMR) and echocardiography examination. SLE patients were grouped according to the quartile of the BMI index, and then CMR morphology, function and histology indicators of each group were compared. The relationship between BMI and extracellular volume fraction (ECV) was explored by using multivariate linear analysis.

    Results

    ·Compared with normal BMI group (18.73?23.00 kg/m2) and high BMI group (>23.00 kg/m2), low BMI group (≤18.72 kg/m2) had higher median ECV (34.33% vs 30.52% vs 31.44%,P=0.007) after being adjusted for age and disease duration. The incidences of right ventricular hypertrophy (33.3%), pulmonary hypertension (26.7%) and edema (6.7%) were lower in low normal BMI group (18.73?20.20 kg/m2) than those in the low BMI group, high normal BMI group (20.21?23.00 kg/m2) and high BMI group. There was a strong correlation between BMI and ECV in long standing SLE patients. When BMI was less than 23.00 kg/m2, it showed a negative correlation (r=-0.597, P=0.009), and a positive correlation (r=0.739, P=0.023) when over 23.00 kg/m2. However, there was no significant correlation between ECV, left ventricular (LV) ejection fraction, LV end-systolic volume and BMI in control group. In the multivariable linear regression, BMI in patients with SLE was associated with elevated ECV independently after being adjusted for age, usage of immunosuppressor and pulmonary artery pressure (BMI>23.00 kg/m2: β=-0.457, P=0.006. BMI≤23.00 kg/m2: β=0.766, P=0.001).

    Conclusion

    ·Cardiac involvement in SLE is closely related to BMI. Low BMI patients should be careful with the cardiac injury. Maintaining BMI at normal low level (18.73?20.20 kg/m2) and avoiding overweight (≤23.00 kg/m2) may be necessary to myocardial protection.

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    Study on the function and prognosis of circular RNA in colorectal cancer tissues based on high-throughput sequencing
    Zhong-mao FU, Zai LUO, Ze-yin RONG, Jian-ming ZHANG, Teng-fei LI, Zhi-long YU, Chen HUANG
    2021, 41 (2):  187-195. 
    doi: 10.3969/j.issn.1674-8115.2021.02.010

    Abstract ( 633 )   HTML ( 3 )   PDF (4389KB) ( 294 )  
    Objective

    ·To reveal the mechanism of colorectal cancer and the association between differential expression of circular RNAs (circRNAs) and patients' prognosis.

    Methods

    ·Colorectal cancer tissues and normal tumor-adjacent tissues were harvested from 12 patients undergoing radical resection of colorectal cancer in the Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, and the expressions of circRNAs were detected by high-throughput sequencing. Function predictions of differentially expressed circRNAs were carried out by gene ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Two circRNAs were selected from the significantly up-regulated and down-regulated circRNAs respectively, and the accuracy of sequencing results was verified in 44 sets of colorectal cancer tissues by real-time fluorescent quantitative PCR (RT-qPCR). The circRNA-miRNA targeting binding network map was constructed by searching the public database for the four circRNAs. Finally, the relationships between differential expression of circRNAs and prognosis were determined based on the patients' clinical data.

    Results

    ·A total of 20 924 differentially expressed circRNAs were detected after high-throughput sequencing. Compared with normal colorectal tissues, there were 373 circRNAs (︱log2FC︱>1, P<0.05) abnormally and significantly expressed in colorectal cancer tissues, of which 243 were significantly up-regulated and 130 were significantly down-regulated. In 44 pairs of colorectal cancer samples, the results verified by RT-qPCR were basically consistent with the sequencing data. After the circRNA-miRNA-mRNA interactions being plotted, it was found that miRNA and target genes associated with circRNA may play an important role in the pathogenesis of colorectal cancer. Combined with the prognosis information, the patients with high expression of hsa_circ_0023984 or hsa_circ_0008192 had poorer prognosis while patients with high expression of hsa_circ_0020093 or hsa_circ_0069922 had better prognosis.

    Conclusion

    ·Abnormally expressed circRNAs in colorectal cancer tissues lay a foundation for further studies on the occurrence and development of colorectal cancer, and provide valuable information for the development of new clinical diagnostic markers and treatments in the future.

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    A pilot study on the efficacy and safety of anlotinib in the treatment of refractory natural killer/T-cell lymphoma
    Gao-yang LI, Ji-feng JIANG, Chuan-xu LIU, Wen-hao ZHANG, Yang ZHU, Yu-jie MA, Rong TAO
    2021, 41 (2):  196-201. 
    doi: 10.3969/j.issn.1674-8115.2021.02.011

    Abstract ( 791 )   HTML ( 3 )   PDF (2839KB) ( 321 )  
    Objective

    ·To observe the efficacy and safety of anlotinib in the treatment of refractory natural killer/T-cell lymphoma (NKTCL).

    Methods

    ·The patients who had been pathologically diagnosed as having NKTCL with measurable/assessable lesions and some organ function reserve after failing in L-asparaginase-containing regimen were recruited in this study from August 2018 to December 2019 in the Outpatient Department of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. They were given anlotinib (12 mg/d) alone or anlotinib (10 mg/d) with programmed death-1 (PD-1) monoclonal antibody until the disease progression or intolerable adverse reactions. Responses were evaluated as per Lugano 2014 criteria. Adverse reactions were assessed according to Common Terminology Criteria for Adverse Events of National Cancer Institute, USA (version 4.03). Kaplan-Meier method was used for survival analysis.

    Results

    ·Twelve patients were included in this study with a median age of 44 years, and 9 patients were males. Among them, 6 patients received anlotinib monotherapy, and 6 patients received anlotinib combined with PD-1 monoclonal antibody therapy. Treatment-related adverse events were observed in all 12 subjects without unexpected adverse reactions. The grade 3 adverse events included hypertension (2 cases) and hyponatremia (1 case). There were 50.0% patients obtaining objective responses with 33.3% in the anlotinib monotherapy group and 66.7% in the combined treatment group. The median progression-free survival was 3.0 months and the median overall survival (OS) was 3.0 months. The median OS of the patients receiving anlotinib alone was 2.8 months, while it was 8.0 months in the patients receiving anlotinib combined with PD-1 monoclonal antibody. The median OS of the responding patients was 8.0 months, while it was 2.8 months in the non-responding patients.

    Conclusion

    ·Anlotinib may be a promising drug for the treatment of refractory NKTCL, which has a potentially synergistic effect with PD-1 monoclonal antibody; the overall safety of the drug is good, and patients generally tolerate it.

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    Biological characteristics and surgical treatment results of stage Ⅰ esophageal squamous cell carcinoma
    Xiao-bin ZHANG, Peng LIU, Zhi-chao LIU, Yang YANG, Bin LI, Yi-feng SUN, Rong HUA, Xu-feng GUO, Yi HE, Hai-yong GU, Zhi-gang LI
    2021, 41 (2):  202-209. 
    doi: 10.3969/j.issn.1674-8115.2021.02.012

    Abstract ( 566 )   HTML ( 7 )   PDF (2024KB) ( 197 )  
    Objectives

    ·To review the results of surgical treatment for the patients with stage Ⅰ esophageal squamous cell carcinoma, analyze the clinical biological characteristics, and determine whether surgical treatment is a recommended curative strategy.

    Methods

    ·A total of 379 patients undergoing esophagectomy with stage Ⅰ squamous cell esophageal carcinoma from 2015 to 2019 in Shanghai Chest Hospital, Shanghai Jiao Tong University, were reviewed. The stage definition was determined according to the 8th edition of the American Joint Committee on Cancer (AJCC ) cancer staging manual. Survival was calculated using the Kaplan-Meier method and was then compared by the Log-rank test. Univariate and multivariate analysis with the Cox proportional hazards model was used to investigate the effect of different factors on survival, including age, gender, pathological T stage, clinical T stage, tumor diameter, the number of dissected lymph nodes.

    Results

    ·Three hundred and seventy-nine patients were included, accounting for 11.9% of all of patients undergoing esophagectomy during the same period. Male accounted for 79.2%. Tumors were located in the upper, middle, and lower segments of thoracic esophagus at 14.2%, 43.8%, and 42.0%. A total of 81.5% of patients underwent minimally invasive surgery. The R0 resection rate was 96.0%. The average number of lymph node dissections was 18.0±9.3. The incidence of postoperative complications of the Clavien-Dindo grade Ⅲ or higher was 20.8%. The incidences of anastomotic fistula, recurrent laryngeal nerve injury, pneumonia, and respiratory insufficiency were 12.4%, 14.2%, 13.5% and 2.9%, respectively. The 30-d and 90-d mortality rates were 0.5% and 1.3%, respectively. Postoperative surgical pathology showed that T1a, T1b and T2 ratios were 20.6%, 69.4% and 10.0%. The diameter of tumor in surgical sample was (2.1±1.1) cm, but larger in preoperative endoscopy evaluation [(3.2±2.2) cm], and the lymphovascular invasion rate was 5.8%. The follow-up time was 1 to 61 months, and the median follow-up time was 24 months. During the follow-up, the overall recurrence rate was 8.2%, and the local recurrence rate and distant metastasis rate were 7.4% and 2.9%, respectively. Univariate analysis showed that the factors of age and number of dissected lymph nodes were related to overall survival (OS) (P=0.025, P=0.011), while clinical and pathological T stage and number of dissected lymph nodes were related to disease-free survival (DFS) (P=0.017, P=0.005, P=0.001). Multivariate analysis showed that the independent risk factors for OS were older than 65 years, less than 15 lymph node dissections. The independent risk factors for DFS were less than 15 lymph node dissections, clinical stage T2 or T3.

    Conclusions

    ·Patients with stage Ⅰ esophageal squamous cell carcinoma can obtain satisfactory tumor control and long-term survival after surgical treatment based on minimally invasive surgery. More thorough lymph node dissection would be the key to improve the current prognosis.

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    Value of pregnancy lipid tolerance test in predicting risk of gestational diabetes mellitus
    Qing LIU, Wen CAI, Rui-qing ZHANG, Cong LU, Jia-rong ZHANG, Xian-ming XU
    2021, 41 (2):  210-216. 
    doi: 10.3969/j.issn.1674-8115.2021.02.013

    Abstract ( 639 )   HTML ( 7 )   PDF (1707KB) ( 313 )  
    Objective

    ·To explore the value of gestational oral lipid tolerance test (OLTT) in predicting the risk of gestational diabetes mellitus (GDM).

    Methods

    ·From May 2019 to December 2019, 71 pregnant women were recruited in Shanghai General Hospital. OLTT was performed during 14-20 gestational weeks. Triacylglycerol (TAG), free fat acid (FFA) , and small dense low density lipoprotein (sd-LDL) were tested on an empty stomach in the morning and 2 and 4 h after eating a high-fat meal. According to the oral glucose tolerance test (OGTT), the pregnant women were divided into GDM group (n=22) and control group (n=49). General indicators such as age; and the levels of TAG, FFA and sd-LDL on an empty stomach and after a fat meal (2 and 4 h) were compared between the two groups. According to the median of fasting and postprandial (2 and 4 h) TAG, FFA, and sd-LDL in OLTT, the pregnant women were divided into different groups. OGTT blood glucose (including fasting blood glucose, 1 h blood glucose, and 2 h blood glucose) , homeostatic model assessment for insulin resistance (HOMA-IR) and the incidence of GDM were compared between the groups. The area under curve (AUC) of each indicator against GDM was compared by receiver operator characteristic (ROC) curve.

    Results

    ·There was no statistical difference in general indicators such as age between the GDM group and the control group (P>0.05). The fasting and postprandial (2 and 4 h) TAG, sd-LDL and postprandial 4 h FFA in the GDM group were significantly higher than those in the control group, and the differences were statistically significant (all P<0.05). There was no significant difference between the two groups in fasting and 2 h FFA after meal (both P>0.05). The fasting blood glucose level of the fasting high TAG group was significantly higher than that of the fasting low TAG group, and the difference was statistically significant (P<0.05). However, there was no statistically significant difference in blood glucose at 1 h and 2 h between the two groups (both P>0.05). The fasting blood glucose and 1 h blood glucose of the 2 h high TAG group were significantly higher than those of the corresponding low TAG group, and the differences were statistically significant (both P<0.05). The OGTT fasting and 1 h blood glucose levels of the 4 h high TAG group were significantly higher than those of the corresponding low TAG group, and the difference was statistically significant (both P<0.05). The HOMA-IR of all high TAG groups was significantly higher than that of the corresponding groups (all P<0.05). The HOMA-IR of all high sd-LDL groups was significantly higher than that of the corresponding group (all P<0.05). There was no significant difference in the incidence of GDM between the fasting high TAG group and the fasting low TAG group (P>0.05). After meals (2 and 4 h), the incidence of GDM in pregnant women in the high TAG group was higher than that in the corresponding low TAG group (P<0.05). ROC curve analysis showed that the AUC of 4 h FFA versus GDM was the largest and was statistically significant (P<0.05).

    Conclusion

    ·Glycolipid metabolism in pregnant women is closely related. Pregnant women with GDM already show abnormal lipid metabolism during the second trimester (before OGTT examination). OLTT during 14-20 weeks of gestation can be used as a supplement to fasting blood lipid testing, and has important value in GDM risk prediction, and can identify high-risk of GDM in advance.

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    Public health
    Epidemiological survey of periodontal health in patients with type 2 diabetes mellitus of different ages
    Yuan-sen DING, Feng WANG, Jia-yue SUN, Zheng-wei SHAO, De-rong ZOU, Jia-yu LU
    2021, 41 (2):  217-222. 
    doi: 10.3969/j.issn.1674-8115.2021.02.014

    Abstract ( 623 )   HTML ( 7 )   PDF (1660KB) ( 327 )  
    Objective

    ·To investigate the periodontal health status of different age groups with type 2 diabetes mellitus, and to explore the influence of age on the prevalence of periodontitis in diabetic patients and the related risk factors.

    Methods

    ·Periodontal examination and questionnaire survey were conducted on patients with type 2 diabetes mellitus who visited the Department of Endocrinology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University from November 2018 to December 2018. The periodontal indexes of index teeth were examined and scored, including probing depth, bleeding on probing, clinical attachment loss (CAL), calculus index (CI) and plaque index (PLI). According to the diagnostic criteria of periodontitis, the subjects were divided into periodontitis group and non-periodontitis group. The prevalence of periodontitis and related periodontal indexes in patients with type 2 diabetes mellitus of different ages were compared.

    Results

    ·In the 916 patients with type 2 diabetes mellitus, the difference of age between the periodontitis group and non-periodontitis group was statistically significant (χ2=100.1, P=0.001). Multivariate Logistic regression analysis indicated that age was a high-risk factor for type 2 diabetic periodontitis (P=0.001, OR=2.13, 95%CI 1.79?2.55). Compared with younger patients with diabetes mellitus, elderly patients with diabetes mellitus were more likely to have periodontal symptoms such as gingival bleeding (χ2=36.4, P=0.001), tooth loosening (χ2=25.9, P=0.002) and masticatory weakness (χ2=12.3, P=0.006). There were significant differences in PLI (χ2=8.3, P=0.041), CI (χ2=12.8, P=0.005) and CAL (χ2=32.5, P=0.001) among diabetic patients of different ages. There were significant differences in periodontal health care measures, such as brushing teeth (χ2=18.8, P=0.001), rinsing mouth with water (χ2=21.8, P=0.001) and frequency of tooth brushing (χ2=24.0, P=0.001).

    Conclusion

    ·The age of diabetic patients is a risk factor affecting the prevalence rate and severity of periodontitis. It is necessary to pay attention to the periodontal health of elderly diabetic patients and carry out targeted oral health care.

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    Correlation between healthy vascular aging and prevalent cardiovascular disease risk in middle-aged and elderly people in the community of Shanghai
    Hua-jie DAI, Li-ping XUAN, Jia-li XIANG, Hong LIN, Zhi-yun ZHAO, Tian-ge WANG, Mian LI, Yu XU, Jie-li LU, Wei-qing WANG, Yu-fang BI, Min XU
    2021, 41 (2):  223-227. 
    doi: 10.3969/j.issn.1674-8115.2021.02.015

    Abstract ( 740 )   HTML ( 5 )   PDF (1097KB) ( 275 )  
    Objective

    ·To study the correlation between healthy vascular aging (HVA) and prevalent cardiovascular diseases (CVDs) risk in middle-aged and elderly people in the community of Shanghai.

    Methods

    ·A total of 9 922 participants aged 40 and above who lived in a Jiading community of Shanghai were included. The questionnaire interview, physical examination, biochemical index detection and brachial-ankle pulse wave velocity (baPWV) measurement were conducted in all participants. According to HVA status, the participants were divided into HVA group and non-HVA group. HVA was defined as baPWV≤15.20 m/s with no history of hypertension. The CVDs include stroke, myocardial infarction and coronary atherosclerotic heart disease. Logistic regression model was used to analyze the correlation between HVA and prevalent CVDs risk.

    Results

    ·Compared with those in the non-HVA group, the age, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, low density lipoprotein-cholesterol, fasting blood glucose, serum creatinine, baPWV and prevalence of diabetes mellitus and lipid disorders in the HVA group were lower, and the proportion of education level (high school or above) and estimated glomerular filtration rate in the HVA group were higher in both men and women (all P=0.000). Logistic regression analysis showed that after multiple confounding factors being adjusted, prevalent CVDs risk in the HVA group was significantly lower than that in the non-HVA group (OR=0.53, 95%CI 0.41?0.69, P=0.000).

    Conclusions

    ·HVA is significantly associated with a lower risk of CVDs in middle-aged and elderly people (aged≥40) in the community of Shanghai, which suggests that HVA can be used as a potential indicator of CVDs prevention.

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    Review
    Progress and prospect of in situ bioprinting
    Wen-tao LI, Jin-wu WANG
    2021, 41 (2):  228-232. 
    doi: 10.3969/j.issn.1674-8115.2021.02.016

    Abstract ( 857 )   HTML ( 13 )   PDF (1022KB) ( 472 )  

    Bioprinting is a new biological manufacturing technology, which opens up new ways for regenerative therapy. The purpose of bioprinting is to create the internal plants in vitro. However, it is difficult to culture and vascularize printed tissue in vitro. In order to overcome this difficulty, in situ printing is presented to print the tissue directly on the injured or defective site, using the natural microenvironment in vivo to make the printed tissue mature. This article reviews the technology, advantages and research status of in situ bioprinting and briefly introduces the future direction of in situ bioprinting.

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    Application of proteomics to the study of gynecological diseases
    Yuan-xin HUANG, Dong-mei LAI
    2021, 41 (2):  233-240. 
    doi: 10.3969/j.issn.1674-8115.2021.02.017

    Abstract ( 870 )   HTML ( 18 )   PDF (1808KB) ( 408 )  

    At present, proteomics is one of the core contents of biomedical research. Its research includes the exploration of biological processes such as signal transduction, cell proliferation and differentiation, protein translation and modification, as well as the search for biomarkers and drug targets of diseases. This review summarizes the application of mass spectrometry-based proteomics to the studies of pathogenesis and biomarkers of common gynecological diseases, including polycystic ovary syndrome, premature ovarian insufficiency, ovarian cancer, endometrial cancer and cervical cancer.

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    Research advances in inflammatory mechanism of anhedonia
    Ze-nan WU, Chen ZHANG
    2021, 41 (2):  241-245. 
    doi: 10.3969/j.issn.1674-8115.2021.02.018

    Abstract ( 817 )   HTML ( 7 )   PDF (1085KB) ( 376 )  

    Anhedonia, a typical symptom of many mental diseases, is also an important indicator for treatment outcome. Further exploration of the mechanism of anhedonia and clear definition and illustration of its pathophysiological basis are helpful to the diagnosis and treatment of related diseases. In recent years, converging evidence has implicated that inflammation-driven alterations in kynurenine pathway (KP) and tetrahydrobiopterin (BH4) metabolism lead to nerve injury and disturbance of neurotransmitter in reward circuit, which is closely related to the emergence and development of anhedonia. Therefore, this review aims to summarize the research advances in the inflammatory mechanism of anhedonia, with the emphasis on both KP and BH4 metabolism.

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    Research progress in anti-tumor effect and mechanism of baicalin
    Meng-ke LIU, Meng-meng JI, Lin CHENG, Jin-yan HUANG, Xiao-jian SUN, Wei-li ZHAO, Li WANG
    2021, 41 (2):  246-250. 
    doi: 10.3969/j.issn.1674-8115.2021.02.019

    Abstract ( 897 )   HTML ( 11 )   PDF (1057KB) ( 334 )  

    Baicalin is one of the flavonoids extracted from the root of Chinese herb Scutellariabaicalensis, which is proved to be an effective component in fields of anti-oxidant, anti-inflammation and anti-virus. Based on further studies, baicalin is gradually known to have anti-tumor function. It has an impact on tumor via multiple mechanisms such as induction of tumor cell cycle arrest, induction of apoptosis of tumor cell, inhibition of tumor metastasis and regulation of tumor microenvironment, ranking it a hotspot in Chinese medicine of anti-tumor therapy. This article comprehensively reviews the previous studies on the anti-tumor effect of baicalin, in order to promote understanding of its anti-tumor mechanisms and provide a new insight in anti-tumor therapy.

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    Application of skin autofluorescence detection technique to diagnosis of diseases
    Lin-xiu-mei GUO, Yi-xin ZHANG
    2021, 41 (2):  251-256. 
    doi: 10.3969/j.issn.1674-8115.2021.02.020

    Abstract ( 1068 )   HTML ( 5 )   PDF (1170KB) ( 526 )  

    Skin is the largest organ of human body. Its histological changes may reflect local lesions and serve as the manifestation of systemic diseases. Some molecules in the skin can absorb exciting light of a specific wavelength and emit emission light with a longer wavelength. These molecules are called endogenous fluorophores, and the emission light is called skin autofluorescence (SAF). Different endogenous fluorophore has its specific fluorescence spectrum. When the skin undergoes pathological changes, the content of certain endogenous fluorophores in the skin will change, and even new endogenous fluorophores will be produced. SAF detection technique is a non-invasive, convenient and low-cost optical measurement without toxic side effects, which contains autofluorescence imaging and autofluorescence spectroscopy. It plays a vital and distinctive role in the diagnosis and differential diagnosis of various skin diseases and evaluation of skin pathological changes by analyzing the fluorescence intensity and the excitation or emission spectrum of skin endogenous fluorophores, especially in the early diagnosis of the disease and long-term follow-up after treatment. So far, SAF technology has been used in differential diagnosis of psoriasis, atopic dermatitis, contact dermatitis and other types of inflammatory dermatosis, in monitoring the treatment effect, quantitatively evaluating skin wound healing and scar fibrosis and predicting the type of scar formation, in quantifying and calibrating skin aging and photoaging, in differential diagnosis of multiple types of benign or malignant skin tumors, in guidance of the scope of resection in surgical operations, etc. In addition, SAF produced by advanced glycation end products can also be used as one of the risk grading indicators for various system diseases such as endocrine system, nervous system, cardiovascular system, and urinary system. This article briefly introduces the principle of SAF detection techique, reviews the application of SAF technology to the diagnosis of diseases, supplements the application of other systemic diseases and provides an outlook on the future development of SAF detection technique, in order to provide reference for related medical fields.

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    Research progress in liver transplantation for acute-on-chronic liver failure
    Tian-yi ZHANG, Ye-ping YU, Qiang XIA, Hua-lian HANG
    2021, 41 (2):  257-261. 
    doi: 10.3969/j.issn.1674-8115.2021.02.021

    Abstract ( 957 )   HTML ( 11 )   PDF (1585KB) ( 320 )  

    Acute-on-chronic liver failure (ACLF), caused by various factors, is a rapid decompensation of liver function based on chronic liver disease, which is often accompanied by multiple organ failure and high short-term mortality. So far, there is no effective treatment except liver transplantation, which is the only possible cure. The evaluation before surgery is critical. Due to the large amount of hepatitis B virus (HBV) patients in our country, the evaluation of HBV-related ACLF (HBV-ACLF) is important. Systems like COSSH-ACLF, and CLIF-ACLF could be used for the evaluation. For the timing of surgery, transplantation at the state of ACLF-2 may have more benefit for patients but the conclusion need more research to prove. During the perioperative period, management of organ failure and basic disease is needed. The timing of dissociation of the receptor and trimming of the donor need to be carefully managed during the surgery. After the surgery, beside the usual complication of liver transplantation, events such as infection, organ failure, hepatic encephalopathy should be dealt with. The condition of organ failures before and after liver transplantation is associated with the long-term mortality of patients.This article aims to make review on the assessment before liver transplantation, timing of transplantation, perioperative management, notice during surgery and complication after surgery based on massive clinical experience and plenty of document readings.

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    Overview of the application of artificial intelligence to radiology of the musculoskeletal system
    Xiao-min LI, Yang QU, Shao-ting ZHANG, Liang ZHAO, Chang LIU, Shuai-ning XIE, Ke-rong DAI, Song-tao AI
    2021, 41 (2):  262-266. 
    doi: 10.3969/j.issn.1674-8115.2021.02.022

    Abstract ( 911 )   HTML ( 8 )   PDF (1072KB) ( 801 )  

    Musculoskeletal diseases are diverse. Medical imaging examination is the primary means of disease diagnosis. Reasonable selection of image post-processing methods can provide reliable evaluation basis for disease diagnosis, surgery and prognosis. As a new stage of the development of computer science, artificial intelligence technology can efficiently and accurately preprocess and analyze images, and assist clinicians in diagnosis and treatment. It will bring new opportunities for the development of musculoskeletal imaging. This paper reviews the current situation and challenges of artificial intelligence in the field of imaging diagnosis of musculoskeletal system diseases, in order to provide some reference for the relevant research scholars.

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    Research progress in epigenetics of obsessive-compulsive disorder
    Liang-jun LIN, Wei-di WANG, Pei WANG, Guan-ning LIN, Zhen WANG
    2021, 41 (2):  267-272. 
    doi: 10.3969/j.issn.1674-8115.2021.02.023

    Abstract ( 915 )   HTML ( 23 )   PDF (1819KB) ( 501 )  

    Obsessive-compulsive disorder is a high disabling psychiatric disease, with unknown etiology. Many studies have shown that the pathogenesis of obsessive-compulsive disorder is associated with both genes and the environment. Epigenetics has provided an approach to explaining the influence on individual inheritance caused by environmental factors. Nowadays, several types of research have proved that there are differences in DNA methylation between obsessive-compulsive disorder patients and healthy population, and the DNA methylation may be strongly related to treatment response. Additionally, an increased level of microRNA was found in patients with obsessive-compulsive disorder. This review summaries the studies of epigenetics of obsessive-compulsive disorder and concludes the possible changes in epigenetic modifications to further understand the pathophysiology of obsessive-compulsive disorder.

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    Brief original article
    Evaluation of ocular surface following lip mucosa graft for palpebral margin defect
    Xu-sheng WU, Yue WU, Chun-yi SHAO, Jin LI
    2021, 41 (2):  273-276. 
    doi: 10.3969/j.issn.1674-8115.2021.02.024

    Abstract ( 757 )   HTML ( 1 )   PDF (1098KB) ( 286 )  
    Objective

    ·To analyze the condition of ocular surface and tear film after reconstruction of palpebral margin with lip mucosa graft.

    Methods

    ·Fifteen patients with palpebral margin defect who were treated in the Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from November 2017 to December 2019 were selected. All patients underwent the lip mucosa graft for palpebral margin reconstruction. A series of ocular surface examination, some ophthalmological physical examination and a questionnaire were prepared for each patient 6?8 weeks after surgery. The ocular surface examination was constituted of tear meniscus height (TMH), tear break-up time (BUT) and Schirmer test. The ophthalmological physical examination included affected palpebral fissure height (PFH) and levator function (LF). Finally, Ocular Surface Disease Index (OSDI) was used as a questionnaire.

    Results

    ·There was no significant difference in TMH between fellow eyes and operated eyes [(0.24±0.07) mm vs (0.23±0.11) mm, P=0.316]. There was no significant difference in BUT between fellow eyes and operated eyes [(10.75±2.31) s vs (7.75±2.05) s, P=0.065]. There was no significant difference in the result of Schirmer text between fellow eyes and operated eyes [(10.20±1.96) mm/5 min vs (9.33±2.04) mm/5 min, P=0.376]. There was no significant difference in PFH between fellow eyes and operated eyes [(10.16±1.18) mm vs (10.11±2.11) mm, P=0.761]. There was no significant difference in LF between fellow eyes and operated eyes [(9.59±0.93) mm vs (9.03±1.02) mm, P=0.552]. The score of OSDI was 26.44±3.88 in average.

    Conclusion

    ·The lip mucosa graft for treating palpebral margin defects gives a satisfactory result in tear film stability and binocular symmetry. Patients may have dry eyes according to the score of OSDI 6?8 weeks after surgery.

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    Case report
    Application of changing the expansion stress point to the treatment of blood flow disorder of skin and soft tissue expander
    Rao FU, Chuan-qi LIU, Bin FANG, Ru-lin HUANG, Qing-feng LI, Yun XIE
    2021, 41 (2):  277-279. 
    doi: 10.3969/j.issn.1674-8115.2021.02.025

    Abstract ( 875 )   HTML ( 0 )   PDF (1911KB) ( 197 )  

    The case is a 10-year-old male patient with facial scar deformity, who was admitted to the hospital 6 years after burns. Bilateral soft tissue expanders were implanted on his neck in order to improve facial scars. Later, the local hypertonicity, thinning of the skin and blood flow disorder of the expanded skin during the water injection were found and the existing treatments were not effective. The patient was re-admitted to hospital and a customized neck expander was replaced under local anesthesia to change the local stress of the weak point and complete further expansion. The expander had a water injection volume of 1 200 mL in the end. After that, the flap transfer repair operation was successfully completed. The clinical data of the case and the treatment of blood flow disorder caused by the implantation of the expander can provide reference for other surgeons.

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    Clinical and genetic analysis of one case of cartilage-hair hypoplasia
    Yi YANG, Wen-jun JIANG, Hui-wen ZHANG
    2021, 41 (2):  280-284. 
    doi: 10.3969/j.issn.1674-8115.2021.02.026

    Abstract ( 924 )   HTML ( 5 )   PDF (2757KB) ( 245 )  

    The main symptom of a female pediatric patient was severely short stature. Ultrasound examinations during pregnancy showed that the limbs were short. The patient was characterized by sparse, fine, and silky hair and prenatal onset of disproportionate short-limb short stature. Radiographic findings showed metaphyseal dysplasia with epiphyseal in terminal femur and proximal tibia. Whole exon sequencing of DNA from peripheral blood was negative. However, sanger sequencing confirmed that the patient had carried g.181G→A/g.255C→T compound heterozygous variants of RNA component of mitochondrial RNA processing endoribonuclease (RMRP) gene, which is a non-coding RNA in human genome. The g.255C→T was a novel mutation. The clinical manifestations of cartilage-hair hypoplasia (CHH) are complex and typical symptoms can help diagnose the disease. CHH should be considered as a differential disease when whole exon sequencing was negative in patients with suspected bone disease. Sanger sequencing test can help confirm the diagnosis, contributing to evaluating the prognosis and prenatal diagnosis. Discovery of the novel variants has enriched the variant spectrum of CHH.

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