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Construction of prognostic risk score model of colorectal cancer gene signature based on transcriptome dysregulation
Ru-juan BAO, Hui-fang CHEN, Yu DONG, You-qiong YE, Bing SU
2021, 41 (3):  285-296.  doi: 10.3969/j.issn.1674-8115.2021.03.001
Abstract ( 290 )   PDF (11478KB) ( 23 )  
Objective

·To construct colorectal cancer (CRC) prognostic risk score model, analyze the significant differences of cancer hallmark signaling pathway or biological process among CRC patients with different scores, and predict the immunotherapy effect of the model on other cancer patients.

Methods

·Eight independent CRC microarray datasets and two CRC RNA-seq datasets were collected from a public database. Differentially expressed genes (DEGs) in each CRC dataset were screened. Based on DEGs with intersection from different datasets, univariate Cox regression model was used to screen the genes associated with adverse prognosis. LASSO regression and multivariate Cox regression models were used to construct CRC prognostic risk score model. According to the risk scores, the patients were divided into high risk group and low risk group. The area under the curve (AUC) of receiver operator characteristic curve and Kaplan-Meier (KM) survival analysis were used to evaluate the model performance. Multivariate Cox regression model was used to analyze whether risk score was an independent prognostic factor for CRC. Gene set enrichment analysis (GSEA) was used to analyze the differences of cancer hallmark gene sets-related pathways between the CRC patients in the high risk group and low risk group. KM survival analysis and chi-square test were used to predict the immunotherapy effect of other cancer patients, so as to evaluate the application value of CRC prognostic risk score model.

Results

·Univariate Cox regression analysis showed that 16 genes associated with adverse prognosis were obtained from DEGs with intersection from different datasets. Based on this, a CRC prognostic risk score model containing 8 gene signatures was constructed. In the training set (AUCmax=0.788) and internal/external validation sets (AUCmean>0.600), the model displayed moderate accuracy, and the patients in the low risk group of all the above sets had significantly higher survival rate than those in the high risk group. Multivariate Cox regression analysis showed that risk score was an independent prognostic factor for CRC. GSEA results showed that cancer hallmark gene sets-related pathways were significantly enriched in CRC patients of the high risk group. KM survival analysis and chi-square test showed that other cancer patients in the low risk group had higher survival rate and better immunotherapy effect.

Conclusion

·The CRC risk score prognosis model containing 8 gene signatures is successfully constructed, which can provide reference for improving the prognosis of CRC patients and predicting the immunotherapy effect on other cancer patients.

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Basic research
Construction of inducible CRISPR/Cas9 system for studying gene function in mouse
Yan-na ZHAO, Rong QIU, Nan SHEN, Yuan-jia TANG
2021, 41 (3):  297-301.  doi: 10.3969/j.issn.1674-8115.2021.03.002
Abstract ( 295 )   HTML ( 1 )   PDF (1811KB) ( 24 )  
Objective

·To construct inducible CRISPR/Cas9 system for studying gene function in mouse immune cells, combining Dox-inducible single guide RNA (sgRNA) expression vector with Cas9 transgenic mice.

Methods

·U6-TetO-sgRNA and EF1α-T2A-Puro-BFP-T2A-TetR fragments were obtained by gene synthesis. The two synthetic fragments were assembled into the retroviral vector backbone by using homologous recombination. sgRNA targeting protein coding region of F4/80 and non-targeting control (NC) were designed. Bone marrow cells were isolated from Cas9 transgenic mice and transfected with retrovirus expressing sgRNA. The experimental conditions were divided into Dox-added group (Dox +) and non Dox-added group (Dox-). The knockout effect was tested by flow cytometry and T7 endonuclease Ⅰ (T7EⅠ) experiments.

Results

·①Dox-inducible sgRNA retroviral vector and Cas9 transgenic mice were successfully constructed. ② The result of flow cytometry showed that F4/80 was only knocked out in the F4/80Dox+ population, but not in NC Dox-, NC Dox+ and F4/80 Dox- populations. ③ T7EⅠ results showed that the DNA was cut into two bands in the F4/80Dox+ group, while the DNA band was intact in the F4/80 Dox- group.

Conclusion

·An inducible CRISPR/Cas9 system combining Dox-inducible sgRNA retroviral vector with Cas9 transgenic mice are successfully constructed. With this system, inducible gene knockout in mouse immune cells are successfully achieved.

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Array detection and expression verification of DNA damage repair related genes in oral leukoplakia cancerization
Wei LIU, Min-wen ZHU, Lan WU
2021, 41 (3):  302-307.  doi: 10.3969/j.issn.1674-8115.2021.03.003
Abstract ( 279 )   HTML ( 3 )   PDF (2109KB) ( 11 )  
Objective

·To study the gene expression profile of DNA damage repair in the occurrence and development of oral leukoplakia (OL) and to verify the expression of mRNA and protein of key genes, ataxia-telangiectasia mutated (ATM) and histone variant H2A family member X (H2AX).

Methods

·Affymetrix HTA 2.0 array was used to detect the high-throughput transcriptome of normal mucosa (n=3), low-risk leukoplakia (n=4), high-risk leukoplakia (n=4) and early squamous cell carcinoma (n=6). Gene Ontology function analysis was used to screen out the genes related to DNA damage repair [|log2(chang fold, FC)|≥2.0 and P<0.05]. Real-time quantitative PCR (qPCR) and Western blotting were used to verify the mRNA and protein expression of key genes (ATM and H2AX) in human normal oral mucosal keratinocytes (HOK), OL (Leuk1) and squamous cell carcinoma cell lines (HN13), respectively.

Results

·DNA damage repair genes abnormally expressed in the occurrence and development of leukoplakia. There were 7 genes with |log2FC|≥2.0 from normal mucosa to low-risk leukoplakia, 7 genes with |log2FC|≥2.0 from low-risk leukoplakia to high-risk leukoplakia, and 52 genes with |log2FC|≥2.0 from high-risk leukoplakia to squamous cell carcinoma. qPCR revealed that the expression of ATM and H2AX in HOK cells, Leuk1 cells and HN13 cells increased stepwise (P<0.05). Western blotting revealed that the expression of γ-H2AX protein was also up-regulated in the HOK cells, Leuk1 cells and HN13 cells (P<0.05). ATM protein was up-regulated in Leuk1 cells compared with HOK cells, but down-regulated in HN13 cells (P<0.05).

Conclusion

·DNA damage repair genes, ATM and H2AX, are involved in the occurrence and development of OL.

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Acetylation involved in bacterial susceptibility to ribosome-targeting antibiotics
Ya-nan LAI, Yu-feng YAO, Xiao-kui GUO, Jin-jing NI
2021, 41 (3):  308-313.  doi: 10.3969/j.issn.1674-8115.2021.03.004
Abstract ( 281 )   HTML ( 0 )   PDF (2774KB) ( 25 )  
Objective

·To investigate the effects of acetylation on the bacterial susceptibility to ribosome-targeting antibiotics.

Methods

·The minimum inhibitory concentrations (MICs) of puromycin, paromomycin, tetracycline and spectinomycin for Salmonella enterica serovar Typhimurium (S. Typhimurium) 14028S were determined by the broth dilution method. The solid mediums with concentration lower than MIC was prepared. The spot dilution assay was employed to determine the susceptibility of S. Typhimuriumstrain 14028S, protein acetyltransferase (pat) knockout strain (Δpat), NAD+-dependent protein deacylase (cobB) knockout strain (ΔcobB) and acetate kinase (ackA) knockout strain (ΔackA) to four kinds of ribosome-targeting antibiotics.

Results

·Increase of acetylation (ΔackA) promoted the susceptibility of S. Typhimurium to puromycin, but promoted the resistance of S. Typhimurium to paromomycin. However, the sensitivity of S. Typhimurium to tetracycline and spectinomycin was not affected by the increase of acetylation (ΔackA or ΔcobB) or decrease of acetylation (Δpat).

Conclusion

·Acetylation is involved in the susceptibility of S. Typhimurium to ribosome-targeting antibiotics, suggesting that acetylation of ribosomal proteins may contribute to bacterial antibiotic sensitivity.

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Expression patterns of interferon regulatory factor 2 binding protein 2 during the early embryonic development of zebrafish
Hai-hong WANG, Shuo GAO, Jun ZHU, Jun ZHOU
2021, 41 (3):  314-319.  doi: 10.3969/j.issn.1674-8115.2021.03.005
Abstract ( 280 )   HTML ( 0 )   PDF (5033KB) ( 7 )  
Objective

·To explore the expression similarities and differences of the two paralogs of interferon regulatory factor 2 binding protein 2 (irf2bp2) gene (irf2bp2a and irf2bp2b) during the early embryonic development of zebrafish.

Methods

·Zebrafish embyos at different developmental stages (embryonic and larval stages) were chosen as research object. The mRNA whole mount in situ hybridization was used to detect the temporal and spatial expression patterns of irf2bp2a and irf2bp2b, and real-time quantitative PCR (qPCR) was used to detect their expression levels.

Results

·Although irf2bp2a and irf2bp2b shared similar expression patterns in the nervous system, eye and pectoral fin, irf2bp2a and irf2bp2b were specifically expressed in liver and stannius corpuscles, respectively, suggesting their expressions were quite unique in certain organs. The results of qPCR showed that both irf2bp2a and irf2bp2b were expressed in the early embryonic development stage, but their expression levels were different.

Conclusion

·Although the functional domains of irf2bp2a and irf2bp2b are highly conserved, the two paralogs of zebrafish irf2bp2 display some distinctions in the expression patterns during the early embryonic development of zebrafish, which suggests that their functions might not be redundant.

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Identification of potential therapeutic target genes in pediatric acute leukemia of ambiguous lineage based on bioinformatics analysis
Ren-yan WU, Xiao-lin GUO, Deng-li HONG, Lei CHEN
2021, 41 (3):  320-327.  doi: 10.3969/j.issn.1674-8115.2021.03.006
Abstract ( 280 )   HTML ( 0 )   PDF (4928KB) ( 10 )  
Objective

·To explore the pathogenetic pathways, unique gene expression profiles related to survival and hub genes in children with acute leukemia of ambiguous lineage (ALAL) by bioinformatics analysis.

Methods

·From TARGET (Therapeutically Applicable Research to Generate Effective Treatment) and GEO (Gene Expression Omnibus), the expression data of patients and healthy individuals were downloaded. The differential analysis of gene expression, as well as its function and survival analysis, were performed by bioinformatics tools, such as limma, clusterProfiler and survival. Finally, the hub genes of ALAL were screened by constructing protein-protein interaction network (PPI).

Results

·Four thousand and fifty-three significant differentially expressed genes were identified in the differential analysis between ALAL group and control group (all P<0.05), of which 1 844 were up-regulated genes and 2 209 were down-regulated genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis indicated that up-regulated genes were related to cell cycle and splicing, while the down-regulated genes were associated with immunity. By comparing the expression profiles with those of other types of leukemia, a unique expression pattern of survival-related genes in ALAL were found. Finally, PPI showed that CXCL8 (C-X-C motif chemokine ligand 8) and LMNA (lamin A/C) were the hub genes of the survival gene network.

Conclusion

·The pathogenesis of ALAL is related to cell cycle and immunity. The poor prognosis of ALAL may be related to the unique expression profile of survival-related genes. CXCL8 and LMNA play an important role in ALAL, and may act as potential therapeutic targets. These results have implications for the mechanism research and clinical treatment of ALAL.

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Clinical research
Changes and significance of CX3CR1 expression in peripheral blood monocyte subsets in patients with coronary atherosclerotic heart disease
Qian ZHAO, Lin GAO, Chang-qian WANG, Jun-feng ZHANG, Hui-li ZHANG, Yang ZHUO
2021, 41 (3):  328-333.  doi: 10.3969/j.issn.1674-8115.2021.03.007
Abstract ( 288 )   HTML ( 2 )   PDF (1060KB) ( 10 )  
Objective

·To investigate the expression and clinical significance of C-C motif chemokine receptor 2 (CCR2) and C-X3-C motif chemokine receptor 1 (CX3CR1) in peripheral blood monocytes subsets in patients with different types of coronary atherosclerotic heart disease (CHD).

Methods

·A total of 63 CHD patients who underwent coronary angiography (CAG) in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January to June 2014 were selected, including 46 patients with acute coronary syndrome (ACS) and 17 patients with stable angina pectoris (SAP). The general data, clinical data and test indexes were collected. Within 24 h after admission, venous blood of the two groups were collected. The expression of CCR2 and CX3CR1 in peripheral blood monocyte subsets was detected by flow cytometry, and monocyte subsets were classified. Serum level of CCL2 (C-C motif chemokine ligand 2) and CX3CL1 (C-X3-C motif chemokine ligand 1) were detected by enzyme-linked immunosorbent assay (ELISA). These patients were followed up for 5 years, and the major adverse cardiac events (MACEs) were recorded.

Results

·Compared with the SAP group, the proportion of CCR2+CX3CR1+ and CCR2-CX3CR1+ monocyte subsets, and the serum levels of CCL2 and CX3CL1 in the ACS group were higher all P<0.05). During the 5-year follow-up, 14 cases in the ACS group and 1 case in the SAP group had MACEs, respectively. Multivariate Logistic regression analysis showed that hypersensitive C-reactive protein level and the proportion of CCR2+CX3CR1- and CCR2-CX3CR1+ monocyte subsets were independent risk factors for the occurrence of MACE in 5 years (all P<0.05).

Conclusions

·Chemokine receptors and chemokines in monocyte subsets alter in different types of CHD. The expression of CX3CR1 of monocyte subsets is possibly related to the long-term outcome of CHD.

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Application of lowering of intrapancreatic plate approach to surgical management of intrapancreatic choledochal cyst
Wei WANG, Xin-sen XU, Chuan-xin YANG, Wei CHEN, Jian WANG
2021, 41 (3):  334-338.  doi: 10.3969/j.issn.1674-8115.2021.03.008
Abstract ( 283 )   HTML ( 0 )   PDF (3301KB) ( 8 )  
Objective

·To investigate the application value of lowering of intrapancreatic plate approach in surgical management of intrapancreatic choledochal cyst.

Methods

·From January 2016 to December 2019, 15 patients with choledochal cyst (Dong type C2) in Renji Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively studied. All patients underwent intrapancreatic choledochal cyst excision through the lowering of intrapancreatic plate approach. Preoperative judgement of junction between choledochal cyst and main pancreatic duct would be verified in operation. The operative success rate, operation time, intraoperative blood transfusion rate, postoperative complications, postoperative pathological results, clinical outcome and follow-up (survival state and long-term complications) were analyzed.

Results

·Preoperative judgement results of junction between choledochal cyst and main pancreatic duct were confirmed in operation. Main pancreatic duct joined with normal bile duct distal to choledochal cyst in 7 (46.7%) patients, and main pancreatic duct joined with choledochal cyst in 8 (53.3%) patients. All the 15 patients underwent successful intrapancreatic choledochal cyst excision through the lowering of intrapancreatic plate approach without remnant intrapancreatic choledochal cysts and main pancreatic duct damage. The operation time was (170.0±22.7) min, and the blood transfusion rate was 0. Postoperative complications occurred in 8 patients, including pancreatic leakage (grade biochemical), pancreatic leakage (grade B), gastroplegia, pancreatic leakage (grade biochemical) combined with bile leakage, intestinal obstruction, pancreatic leakage (grade biochemical) combined with intestinal obstruction, intraperitoneal effusion with infection and incision infection. Postoperative pathological results showed that all patients were diagnosed as choledochal cyst with chronic inflammation of mucosa. After treatment, all patients were cured and discharged.After 5?48 months of follow-up, all patients survived well, without the sign of anastomotic stricture after hepaticojejunostomy, biliary dilatation and carcinogenesis.

Conclusion

·Intrapancreatic choledochal cyst excision through the lowering of intrapancreatic plate approach is safe and effective.

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CBCT effects of different abutment angles on alveolar bone changes in maxillary anterior teeth
Jian-ming YUAN, Bin WEI, Wei-xing XU, Lei ZHANG
2021, 41 (3):  339-343.  doi: 10.3969/j.issn.1674-8115.2021.03.009
Abstract ( 280 )   HTML ( 0 )   PDF (1907KB) ( 6 )  
Objective

·To compare the imaging differences of alveolar bone changes after using different angles of abutment implants in the maxillary anterior area.

Methods

·Forty patients of maxillary anterior area implant restoration at the Second Stomatological Disease Institution of Huangpu District in Shanghai from January 2017 to December 2018 were divided into 2 groups according to the different angle of abutment, with 20 cases in each group, which were treated with the 0° and 25° abutment, respectively. Cone beam computed tomography (CBCT) examination was performed immediately, 6 months, 12 months and 18 months after angular abutment restoration, and the differences of CBCT changes in the thickness and height of labial alveolar bone between the two groups at different periods was measured by self-control study and paired t test.

Results

·CBCT comparison of 0° and 25° groups at 6 months, 12 months and 18 months after restoration showed no significant difference in the thickness and height of alveolar bone in the two groups.

Conclusion

·Change of alveolar bone around the implant can be quantified by using CBCT image examination. When the base angle of the maxillary anterior tooth area is within 25°, the base angle has no significant effect on the change of alveolar bone.

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Efficacy of early ultrafiltration in acute decompensated heart failure patients with volume overload
Qian-li WAN, Jing-yi HU, Jun ZHOU, Miao-miao LI, Yue ZHANG, Fang YUAN
2021, 41 (3):  344-349.  doi: 10.3969/j.issn.1674-8115.2021.03.010
Abstract ( 280 )   HTML ( 0 )   PDF (1358KB) ( 7 )  
Objective

·To investigate the efficacy and safety of early ultrafiltration in acute decompensated heart failure (ADHF) patients with volume overload.

Methods

·One hundred patients with ADHF admitted to cardiac care unit of Tongren Hospital, Shanghai Jiao Tong University School of Medicine from July 2018 to September 2019 were randomly divided into early ultrafiltration group (n=40) and diuretic group (n=60). In the early ultrafiltration group, blood ultrafiltration was performed within 3 d after admission,and diuretic sequential treatment (Torasemide 20?40 mg/d and Tolvaptan 7.5?30.0 mg/d) was given on day 4 to 7. The diuretic group received intensive treatment (Torasemide 20?40 mg/d and Tolvaptan 7.5?30.0 mg/d) after admission. On the 4th and 8th day of treatment, the body mass and urine volume of the two groups were compared; on the 8th day, dyspnea score, internal diameter of inferior vena cava (ICV), inferior vena cava-collapse index (IVC-CI), jugular vein pressure (JVP) and B-type natriuretic peptide (BNP) were compared between the two groups. The readmission rate and mortality of the two groups at 1-month and 3-month follow-up were compared. The heart rate, respiratory rate, blood pressure, serum sodium, serum potassium and serum creatinine levels of the two group on the 8th day of treatment were compared with those before treatment, respectively.

Results

·Compared with the diuretic group, weight loss and urine increase in the early ultrafiltration group on the 4th day and the 8th day showed significant difference (all P<0.05). There were significant differences in the changes of dyspnea score, IVC, IVC-CI, JVP and BNP on the 8th day of treatment between the two groups (all P<0.05). No significant differences were found in the safety indexes in the two groups, and the readmission rate and mortality rate in the two groups at 1-month and 3-month follow-up.

Conclusion

·Early ultrafiltration can effectively remove excess body fluids, reduce body weight, increase the sensitivity of patients to diuretics. It has no effect on blood pressure, electrolytes and renal function.

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Relevance of quantitative PCR detection of mecA and Sa442 genes in sputum samples with clinical MRSA experimental diagnosis
Xiao-yao CAI, Kun-yin LIN, Tao SUN, Li ZHANG, Pei-yi YAN, Shu JIN
2021, 41 (3):  350-354.  doi: 10.3969/j.issn.1674-8115.2021.03.011
Abstract ( 281 )   HTML ( 0 )   PDF (1401KB) ( 11 )  
Objective

·To analyze the infection status and clinical significance of methicillin resistant Staphylococcus aureus (MRSA) by detecting mecA and Sa442 genes.

Methods

·DNA was obtained from sputum samples. The clinical significance of quantitative value of quantitative PCR (qPCR) was analyzed by combining with the results of routine culture and identification of sputum samples.

Results

·There were 1 775 qualified sputum samples. The sensitivity of qPCR was 92.19% (59/64), the specificity was 89.60% (1 533/1 711), the positive predictive value was 24.89% (59/237), and the negative predictive value was 99.67% (1 533/1 538). The results of receiver operating characteristic ( ROC) curve analysis showed that the area under the curve of mecA quantitative value and CT value were 0.755 and 0.770, respectively. The best critical values were 5.59 and 27.1, respectively. The sensitivity was 72.4% and 73.0%, and the specificity was 70.2% and 74.1%, respectively. When only Sa442 gene was positive, methicillin-susceptible Staphylococcus aureus was the main bacteria. When mecA value was greater than 5.59, or CT value was less than 27.1, MRSA culture can be predicted to be positive.

Conclusion

·The quantitative detection of mecA and Sa442 genes in sputum samples can be used to quickly exclude the colonization and infection of MRSA in the early stage, helping to analyze the trend of different culture results.

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Characteristic analysis and comparison of glycolipid metabolism in patients with coronavirus disease 2019 in common condition and severe cases
Jiang YUE, Yong ZHOU, Hua XU, Wen LIU, Xiao-feng HAN, Qing MAO, Ji-dong ZHANG, Jing MA, Han-dong JIANG, Wei LIU
2021, 41 (3):  355-359.  doi: 10.3969/j.issn.1674-8115.2021.03.012
Abstract ( 286 )   HTML ( 0 )   PDF (1185KB) ( 12 )  
Objective

·To analyze and compare the characteristics of glycolipid metabolism between common and severe patients with coronavirus disease 2019 (COVID-19).

Methods

·Thirty-six patients with COVID-19 were hospitalized in the general ward of Wuhan Leishenshan Hospital and fifty severe patients with COVID-19 in intensive care unit (ICU) from February to March, 2020. All the patients were divided into two groups: the common patient group and the severe patient group. Their electronic medical records were extracted and analyzed. The demographic data as well as clinical data, laboratory results, comorbidities and clinical outcomes in the two groups were collected and compared by independent sample t test, non-parametric test as well as χ2 test. From the metabolic point of view, the characteristics of glucose and lipid metabolism in COVID-19 common and severe patients and the possible related factors for patients staying in ICU were analyzed.

Results

·There was no significant difference between the two groups in terms of gender, number of patients with diabetes and coronary heart disease (CAD). The average age of severe patients was significantly older than that of the common patients (P<0.05). The proportion of the severe patients with hypertension (52.0%) was significantly higher than that of the common patients (22.2%) (P<0.05). The lymphocyte count of the severe patients was significantly lower than that of the common patients (P<0.05). There was no significant difference in glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), serum creatinine (Scr) and blood uric acid (BUA) between the two groups. Blood serum albumin (ALB), adjusted calcium concentration (Cac), total cholesterol (TC), triacylglycerols (TAG), high density lipoprotein (HDL) and the low density lipoprotein (LDL) in the severe patients were significantly lower than those in the common patients (all P<0.05). Fasting blood glucose (FBG) in the severe patients was significantly higher than that in the common patients (P=0.001). Multivariate Logistic regression showed that the increase of FBG and the decrease of TC, HDL, LDL, ALB were related to COVID-19 patients staying in ICU.

Conclusion

·There are deteriorative disorders in terms of glucose and lipid metabolism among the severe patients with COVID-19. The FBG, TC, HDL, LDL and ALB may related to the admission of ICU.

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Public health
Effects of individualized nutritional standard meal intervention on the prevention of gestational diabetes in overweight and obese pregnant women
Yue-hua TU, Xiao-jin WANG, Bing-shun WANG
2021, 41 (3):  360-365.  doi: 10.3969/j.issn.1674-8115.2021.03.013
Abstract ( 279 )   HTML ( 0 )   PDF (1402KB) ( 9 )  
Objective

·To explore the effect of individualized nutritional standard meal intervention on weight management and prevention of gestational diabetes mellitus (GDM) in overweight and obese pregnant women.

Methods

·Overweight and obese pregnant women who had established files in Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences from June 2017 to January 2019 with informed consent were randomly divided into intervention group and control group, with 100 cases in each group. The control group received collective health education in nutrition class during pregnancy, and the intervention group received individualized nutrition intervention such as nutritional standard meal on this basis. The weight gains at 13?16, 17?20 and 21?24 weeks of gestation and the incidence of GDM were compared between the two groups.

Results

·The weight gain of the intervention group was lower than that of the control group at 13?24 weeks of gestation (t=4.207, P=0.000). The variation of weight gain between the two groups was the greatest at 17?20 weeks of gestation (F=3.483, P=0.034). The incidence of GDM in the intervention group (16.5%) was lower than that in the control group (38.5%) (χ2=11.773, P=0.001).

Conclusion

·The intervention of individualized nutrition standard meal for overweight and obese pregnant women can help maintain appropriate gestational weight gain and reduce the incidence of GDM.

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Review
Advances in estimating fetal weight by maternal and fetal ultrasound variables
Yi-fei WANG, Yan-ting WU, He-feng HUANG
2021, 41 (3):  366-370.  doi: 10.3969/j.issn.1674-8115.2021.03.014
Abstract ( 286 )   HTML ( 4 )   PDF (1084KB) ( 9 )  

The estimated fetal weight (EFW), using the parameters of pregnant woman and fetuse before birth, plays an important role in helping evaluating fetal development and pregnancy outcome. Various methods have been used to calculate EFW. Predictive accuracy of estimating EFW by using pregnant women's parameters depends on doctors' experience and standardization of measurement. Some appraisal procedures, such as Hadlock formula, which mainly focus on prenatal fetal ultrasound parameters, have been widely used in clinics but still have large errors. Measurements of fetal volume by 3-dimentional ultrasound and magnetic resonance imaging methods show significant improvements, yet they cannot be widely used because of time and economic issues. The prediction coincidence rate of a model with big data based on analysis of neural network, is better than that of traditional ultrasonic detection. It could be a better method of EFW in the future. In summary, accurate evaluation of EFW and its application to obstetric clinic are still major challenges in the future.

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Physiological function of cholesterol sulfate and its role in related diseases
Yue-ting JIANG, Jia-ying NI, Shen-rui GUO, Han LI, Yu-jia ZHUANG, Feng WANG
2021, 41 (3):  371-375.  doi: 10.3969/j.issn.1674-8115.2021.03.015
Abstract ( 285 )   HTML ( 2 )   PDF (1069KB) ( 14 )  

Cholesterol sulfate (CS), synthesized by sulfotransferase (SULT) 2B1b, is an important steroid sulfate and plays important physiological roles in the human body. It is widely distributed in human body, such as skin, adrenal gland, liver, lung, brain and endometrium. CS participates in the formation of cornified envelopes and the expression of keratinocyte differentiation markers in the epidermis, thereby regulating epidermal desquamation and barrier function. CS inhibits T cell signaling during thymocyte development in the immune system, and CS/ Cholesterol ratio directly affects thymic selection for T cells, thereby participating in the shaping of T cell receptor repertoire. CS regulates brain metabolism and exerts neuroprotective effects by reducing oxidative stress, maintaining mitochondrial membrane stability and increasing energy reserves. In addition, CS also contributes to the development of many diseases by regulating the activity of functional proteins. The deletion and mutation of steroid sulfatase (STS) gene, which catalyzes the desulfurization of CS, directly leads to the occurrence of X-linked ichthyosis. CS is involved in the development of Alzheimer's disease by promoting the aggregation of amyloid β - protein (Aβ). CS regulates gluconeogenesis by inhibiting the activation of hepatocyte nuclear factor 4α (HNF4α). Thus CS is expected to treat type 2 diabetes. CS has abnormal expression in a variety of cancers, and can interact with matrix metalloproteinase-7 (MMP-7) to induce the aggregation and metastasis of cancer cells. The main challenges and research priorities at this stage are to reveal specific molecular mechanisms under different physiological and pathological conditions and to design feasible clinical treatments.

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Research progress in cue-reactivity of addictive substance and its neural mechanism
Ping-yuan YANG, Hai-feng JIANG, Min ZHAO
2021, 41 (3):  376-379.  doi: 10.3969/j.issn.1674-8115.2021.03.016
Abstract ( 286 )   HTML ( 3 )   PDF (971KB) ( 14 )  

Cue-reactivity of addictive substance is a kind of evoked physiological, behavioural and neural responses when an individual is exposed to cues previously associated with addictive substance taking. Cue-reactivity is one of the main features of addiction. It can evoke craving and plays an important role in relapse. However, the neuromechanism is still unknown. The review summarizes recent research progress in the neuromechanism of cue-reactivity and the condition of clinical therapies based on cue-reactivity, which helps deeply understand the development of addiction and set effective clinical intervention strategy.

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Research progress of hydroxychloroquine in reproductive immunology
Xi KOU, Ai-min ZHAO
2021, 41 (3):  380-385.  doi: 10.3969/j.issn.1674-8115.2021.03.017
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Hydroxychloroquine (HCQ) is a kind of synthetic 4-aminoquinoline antimalarial drugs. In recent years, other pharmacological effects of HCQ, such as immunomodulatory, immunosuppression, anti-inflammation, vascular endothelium protection, anti-thrombus, improving metabolic syndrome, and anti-infection, have been gradually known. At present, HCQ is a first-line drug for systemic lupus erythematosus. And in many guidelines for the treatment of autoimmune diseases, HCQ is recommended during whole pregnancy and lactation. This review mainly expounds the mechanism and research progress of HCQ in reproductive immunology, including pregnancy complicated with autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome and Sjogren's syndrome, as well as unexplained recurrent spontaneous abortion and recurrent implantation failure, and explores the safety and application prospect of HCQ in reproductive immunology.

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Progress in researches on improving engraftment of hematopoietic stem/progenitor cells of cord blood
Liu-xin NING, Si-guo HAO
2021, 41 (3):  386-390.  doi: 10.3969/j.issn.1674-8115.2021.03.018
Abstract ( 272 )   HTML ( 0 )   PDF (1063KB) ( 5 )  

Cord blood transplantation (CBT) has been widely used in the treatment of hematologic malignancies and non-malignant hematologic diseases both in children and adults. Compared with other sources of hematopoietic stem/progenitor cell (HSPC) transplantation, CBT has a higher rate of engraftment failure and delayed hematopoietic system and immune system recovery, thereby increasing the mortality caused by infection and other transplant-related complications. Therefore, how to promote the engraftment of cord blood HSPC has been a hot spot in CBT for many years. The article reviews the latest advances in the strategies to improve the engraftment of HSPC of cord blood.

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Progress of cardioprotection effect of sodium-glucose cotransporter 2 inhibitor on patients with type 2 diabetes
Min SUN, Dong-ying ZHANG
2021, 41 (3):  391-395.  doi: 10.3969/j.issn.1674-8115.2021.03.019
Abstract ( 281 )   HTML ( 0 )   PDF (1076KB) ( 8 )  

As a novel anti-diabetes drug, sodium-glucose cotransporter 2 inhibitor (SGLT2i) can decrease the all-cause mortality, the risk of major adverse cardiac event (MACE) and rate of heart failure hospitalization in patients with type 2 diabetes. Studies found that besides the function of glycemic control, SGLT2i could reduce the preload and afterload of heart, improve the hemodynamics, attenuate myocardial fibrosis and rejuvenate myocardial energetics. In this paper, clinical trials about SGLT2i in recent years and the mechanisms are reviewed to discuss the progress of the cardioprotection effect of SGLT2i on patients with type 2 diabetes.

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Research progress of contrast-enhanced ultrasound in the diagnosis of benign and malignant bladder tumors
Jie YU, Fan LI
2021, 41 (3):  396-399.  doi: 10.3969/j.issn.1674-8115.2021.03.020
Abstract ( 284 )   HTML ( 1 )   PDF (949KB) ( 9 )  

Bladder cancer is the ninth leading cancer in the world, and the most common malignant tumor in urinary system in China. Bladder cancer is originated from mucosal epithelium of the bladder, has a high degree of malignancy and is easy to relapse. Urothelial carcinoma is the most common type. Benign bladder tumor is rare, and surgical removal yields better results. The optimal treatment and patients' prognosis of bladder tumor are attributed to its early detection and accurate diagnosis. Contrast-enhanced ultrasound (CEUS) is a new imaging technique which could dynamically display the microcirculation of tumors and tissues. The advantage of CEUS is good safety, easy manipulation, and repeatable use. CEUS is now playing a more and more significant role in diagnosing bladder tumors. In this article, the application of CEUS to the diagnosis of benign and malignant bladder tumors is reviewed.

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Techniques and methods
Determination of inosine in human plasma by high performance liquid chromatography-tandem mass spectrometry combined with solid-phase extraction
Guan-qin JIN, Li SUN, Ling-hong XIA, Hou-wen LIN
2021, 41 (3):  400-405.  doi: 10.3969/j.issn.1674-8115.2021.03.021
Abstract ( 280 )   HTML ( 0 )   PDF (1588KB) ( 6 )  
Objective

·To establish a solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method for the determination of inosine in human plasma.

Methods

·Inosine and internal standard in human plasma were quantitatively analyzed with electrospray ionization positive ion mode and multiple reaction monitoring scan analysis. The ion pairs used for quantitative analysis were m/z 269.1/137.1 (inosine) and m/z 230.2/112.2 (internal standard). The results of method validation included limit of quantification, accuracy, intra-day and inter-day precision, extraction recovery, and stability tests in different conditions.

Results

·The results of method validation showed that the calibration curve of inosine in human plasma exhibited a good linearity (R2>0.999) over the range from 28.5 to 912.0 ng/mL, and quantitative lower limit was 28.5 ng/mL. Accuracy was 96.9%?103.8%, and the relative standard deviations of intra-day and inter-day precision were both less than 10%. The extraction recovery was between 98.9% and 102.3%. In stability tests (samples stored at room temperature for 4 h, 3 freeze-thaw cycles, -70 ℃ for 7 d and 4 ℃ in autosampler for 24 h), the rates of change of inosine in human plasma were less than 15%.

Conclusion

·The established SPE-HPLC-MS/MS method is simple, rapid, sensitive and accurate, and it is suitable for the clinical monitoring of inosine concentration in human plasma.

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Case report
Airway management in a critically ill patient with novel coronavirus pneumonia undergoing extracorporeal membrane oxygenation
Li ZHU, Yun LI, Hui-qin XI, Wei-jun WANG, Fei CHEN, Zhan-ting LU, Ling XIA, Meng-dian ZHAN, Tian-yao ZHANG
2021, 41 (3):  406-408.  doi: 10.3969/j.issn.1674-8115.2021.03.022
Abstract ( 282 )   HTML ( 0 )   PDF (943KB) ( 7 )  

This article summarizes the nursing experience in a critically ill patient with novel coronavirus pneumonia after extracorporeal membrane oxygenation (ECMO) treatment for lung function improvement. After oral intubation-assisted ventilation, anti-infection, and other symptomatic support treatments, the patient was still unable to breathe without the ventilator. For the sustained carbon dioxide retention and severe gas exchange impairment, he was treated with tracheotomy and ECMO. During the treatment, a series of nursing measures to improve lung function were adopted, such as sputum suction care, atomized inhalation therapy, bronchial irrigation, and lateral ventilation combined with postural drainage. After 7 days of ECMO treatment and nursing, the patient's lung function improved and then he was weaned from the machine.

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Study on interleukin-10 receptor A gene mutations-induced neonatal very early onset inflammatory bowel disease in 2 infants
Yu-jie XIE, Li-juan XIE, Tian-wen ZHU, Yi-wen WANG
2021, 41 (3):  409-412.  doi: 10.3969/j.issn.1674-8115.2021.03.023
Abstract ( 278 )   HTML ( 0 )   PDF (1951KB) ( 7 )  

In April, 2019, a 36-day-old boy having presented chronic bloody diarrhea for 14 d went to hospital. He developed oral ulcer and perianal abscess,and was taken to surgery. The colonoscopy showed severe ulcerations with granuloma in colon and superficial ulceration in ileum. Genetic analysis of the patient showed compound heterozygous mutations in interleukin-10 recepter A (IL-10RA) gene mutation (c.301C>T,c.537G>A ) and the patient was diagnosed with very early onset inflammatory bowel disease (VEO-IBD). Significant growth failure, chronic diarrhea and perianal abscess was administered when he was 6 months old. The patient 2 was a 9-day-old boy and presented fever and cough.Chronic diarrhea and perianal abscess were noted after admission, which didn't respond to broad-spectrum antibiotics. The colonoscopy showed small ulcers in the colon and histology showed chronic active inflammation with cryptitis and granuloma in the colon, consistent with Crohn's disease. IL-10RA gene (c.106G>A,c.299T>G) deficiency was confirmed by sanger sequencing. Thalidomide were used to control intestinal inflammation and hemopoietic stem cell transplantation was planned to be performed at the age of 4 months.

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