Journal of Shanghai Jiao Tong University (Medical Science)

Effect of potential pathogenic gene PDX1 variants of total anomalous pulmonary venous connection on its gene function

FENG Weiqi, ZHANG Qi, WU Yizhuo, LU Yanan, YU Yu

2023, 43 (10): 1219-1226.
doi: 10.3969/j.issn.1674-8115.2023.10.001

Abstract ( 255 )

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Objective ·To explore the possible pathogenic gene of total anomalous pulmonary venous connection (TAPVC) by whole exon sequencing and verify its function. Methods ·One hundred TAPVC children (case group) and one hundred and twenty healthy children (control group) in Xinhua Hospital and Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from 2014 to 2019 were included. The blood samples from the two groups of children were collected, and whole blood genomic DNA was extracted for exon sequencing to screen out the potential pathogenic genes of TAPVC. Harmful mutation sites of pathogenic genes were screened through Mutation Taster, SIFT and PolyPhen-2 websites, and then conducted by Sanger sequencing. The wild-type (wild-type group) and mutant (mutant group) plasmids of PDX1 were transfected into HUVEC cells. Quantitative real-time PCR (qPCR) and Western blotting were used to detect the effects of mutations on mRNA and protein levels of PDX1, respectively. The STRING database was used to analyze the interaction between proteins, and qPCR was used to determine the expressions of downstream genes regulated by PDX1. Results ·Pathogenic PDX1 was found in TAPVC children, and Sanger sequencing revealed two novel variants in the gene: c.C237A (P33T) and c. C237G (P33A). Compared with the wild-type group, there was no significant difference in PDX1 mRNA levels in the two mutant groups, but there was a significant increase in relative protein expression of the CA group and CG group, which was 2.9 and 3.4 times higher than the wild-type group, respectively (P=0.000, P=0.001). Protein interaction analysis demonstrated that PDX1 was associated with SOX17. qPCR results showed that overexpression of PDX1 could downregulate the expression of SOX17 in HUVEC. Conclusion ·The two novel PDX1 missense mutations can affect the process of PDX1 post-transcriptional translation, indicating that PDX1 may participate in the occurrence and development of TAPVC by regulating SOX17.

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Analysis of m⁶A methylation expression profiles in liver tissue of high-fat diet-induced mouse models of NAFLD

LIU Junjun, LU Sumei, ZHANG Bingyang, LI Yongqing, MA Wanshan

2023, 43 (10): 1227-1235.
doi: 10.3969/j.issn.1674-8115.2023.10.002

Abstract ( 405 )

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Objective ·To detect the differences in m⁶A methylation modification and gene expression of liver tissue mRNA in high-fat diet-induced mouse models of non-alcoholic fatty liver disease (NAFLD) using microarray technology. Methods ·The NAFLD models were established in 6-8 weeks old male C57BL/6J mice fed with high-fat chow for 16 weeks (high-fat group, n=10). The basal group (n=10) was given 10% fat diet. Hematoxylin-eosin (H-E) staining was used to assess the histopathological changes in liver tissue and to determine the success of the NAFLD models. The changes of mRNA m⁶A methylation and expression levels in the liver tissues of the two groups were detected by using methylated RNA immunoprecipitation (MeRIP) and microarray expression profiling. Results ·The livers of the mice in the basal group were bright red with few fat deposits, while the livers of the mice in the high-fat group were yellowish with diffuse infiltration and fusion of lipid droplets in the hepatocytes by H-E staining, suggesting that the high-fat diet-induced NAFLD models were successfully constructed. The results of the MeRIP-microarray showed that the m⁶A methylation levels of 320 genes in the livers of mice in the high-fat group were significantly altered compared with those in the basal group (P<0.05 and fold change>1.5), of which 108 genes were up-regulated and 212 genes were down-regulated. Genes with significant differences in m⁶A methylation levels between the two groups were intersected with those with differentially expressed mRNAs, and 163 genes were found to have significant differences in both m⁶A methylation level and mRNA expression level. Conclusion ·The change in m⁶A modification of liver tissue mRNA in the high-fat diet-induced mouse models of NAFLD is significant and the change is associated with the gene expression of mRNA.

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Research on the role of SOX9 in regulating metabolic reprogramming in diffuse large B cell lymphoma

ZHANG Yirong, WEI Weiqing, MA Jiao, ZHANG Xue

2023, 43 (10): 1236-1244.
doi: 10.3969/j.issn.1674-8115.2023.10.003

Abstract ( 341 )

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Objective ·To explore the role played by the differentially expressed SRY-box transcription factor 9 (SOX9) gene in diffuse large B cell lymphoma (DLBCL), particularly in the regulation of metabolic reprogramming in the germinal center B-cell (GCB) like subtype. Methods ·The clinical information and gene expression profile data of 481 DLBCL patients retrieved from the NCICCR-DLBCL database were included. Data analysis and visualisation were performed by using R language version 4.1.3. The classification was performed by using a cell of origin subtype (COO) classification algorithm based on RNA-seq sequencing of expression. ABC/GCB features were used to annotate gene sets, and the classification was verified by gene set enrichment analysis. The ABC and GCB subgroup was dichotomised based on the mean expression of SOX9. Differential analysis was performed by using the DEseq2 package. The relationship between SOX9 and ABC-DLBCL metabolism was analysed by using KEGG (Kyoto Encyclopedia of Genes and Genomes) with the Hallmark annotation set. The survival curves were plotted by using the Kaplan-Meier method. The pan-cancer analysis was performed by using GEPIA2. The microenvironmental scoring analysis was performed by the ESTIMATE package. Results ·Of the 481 DLBCL patient samples, all the patients had RNA-seq expression data, 421 had clinical staging, 335 had international prognostic index (IPI) scores and 234 had survival data. The classification yielded 232 (48.2%) ABC subtypes, 173 (36.0%) GCB subtypes and 76 (15.8%) unclassified, consistent with the proportions declared in the database, and the enrichment analysis was verified to be consistent with the ABC/GCB expression profile. Compared to the high SOX9 expression group, the overall survival was shorter in the low SOX9 expression group and the prognostic score was worse. The pan-cancer analysis showed that this phenomenon was also seen in other tumor types. The differential analysis showed that there were 156 upregulated genes and 1 826 downregulated genes in the GCB subtype in the low SOX9 expression group, compared to the high SOX9 expression group. For metabolic processes, down-regulated genes were enriched in glycolysis. Conclusion ·In the ABC subtype of DLBCL, the SOX9 gene affects the biological features of ABC-DLBCL by regulating metabolic reprogramming, and low expression of SOX9 in DLBCL, possibly caused by high methylation, predicts decreased glycolysis in tumors. The proportion of tumor stromal cells decreases, showing a worse prognosis.

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Effects of Escherichia coli outer membrane vesicles on proliferation of breast cancer cells and tumor growth of tumor-bearing mice

WANG Lanxi, MA Guanrong, JIANG Yongzhu, CHANG Xiulin, FANG Liaoqiong, BAI Jin

2023, 43 (10): 1245-1254.
doi: 10.3969/j.issn.1674-8115.2023.10.004

Abstract ( 332 )

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Objective ·To analyze the effect of Escherichia coli outer membrane vesicle (E.coli-OMV) on the proliferation of 4T1 breast cancer cells in vitro and the inhibition of tumor growth in BALB/c-4T1 tumor-bearing mice in vivo. Methods ·OMVs were collected from the culture supernatant of E.coli and characterized. The uptake of E.coli-OMV by 4T1 cells was detected by fluorescent label tracking method. The effect of E.coli-OMV on 4T1 cell proliferation was detected by CCK-8 method. The effect of E.coli-OMV on 4T1 cell cycle was detected by flow cytometry. The BALB/c-4T1 tumor-bearing mouse models were established by subcutaneous inoculation, and the mice were divided into E.coli-OMV group and Control group, with 10 mice in each group. The mice in the E.coli-OMV group were injected with 0.25 mg/kg E.coli-OMV every 2 d, while the mice in the Control group were injected with equal doses of PBS. The changes in body weight, 40 d survival rate, tumor volume and tumor weight of the two groups of tumor-bearing mice were observed. The pathological morphology of the tumor tissues was evaluated by hematoxylin-eosin staining (H-E staining). The expression of proliferating cell nuclear antigen (PCNA) and CyclinD1 in tumor tissues was observed by immunohistochemical staining. Results ·E.coli-OMVwas spherical membrane vesicle structure with a particle size of (216.00±18.30) nm, which expressed E.coli outer membrane protein A (OmpA) and OmpC. Fluorescence microscopy results showed that 4T1 cells could intake E.coli-OMV. CCK-8 results showed that the inhibitory effect of E.coli-OMV on 4T1 cells was positively correlated with time-dose. Flow cytometry results showed that E.coli-OMV arrested the growth cycle of 4T1 cells in G₀/G₁ phase. In vivo experiments showed that compared with the Control group, body weight of mice in the E.coli-OMV group decreased slightly after the initial injection (P=0.031), and then recovered, while 40 d survival rate increased (P=0.037). The growth of tumor volume and weight of mice in E.coli-OMV group were lower than those in the Control group (P=0.041, P=0.004). Its tumor volume inhibition rate reached 29.69%, and tumor weight inhibition rate reached 49.81%. The results of H-E staining showed that nuclear splitting images of tumor tissues of mice in the E.coli-OMV group decreased compared to the Control group (P=0.038). The results of immunohistochemical staining showed that the positive expression of PCNA and CyclinD1 in the tumor tissues of mice in the E.coli-OMV group decreased compared to the Control group (P=0.031, P=0.002). Conclusion ·Both in vitro and in vivo studies show that E.coli-OMV can significantly inhibit the proliferation of 4T1 cells.

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Screening and functional analysis of mutations in NEUROD1 gene in pedigrees of maturity-onset diabetes of the young

ZHANG Juan, GE Xiaoxu, ZHANG Rong, JIANG Fusong, JIANG Yanyan, LI Ming, LI Tiantian, LIU Chanwei, CHEN Yating, LIU Limei

2023, 43 (10): 1255-1261.
doi: 10.3969/j.issn.1674-8115.2023.10.005

Abstract ( 281 )

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Objective ·To screen the mutations of NEUROD1 gene in families of maturity-onset diabetes of the young (MODY), and investigate the correlation between the mutation and MODY6 and its potential pathogenesis in Chinese. Methods ·PCR-direct sequencing was used for screening NEUROD1 mutations from 96 MODY probands who were negative for mutations in the GCK/MODY2, HNF1A/MODY3 and HNF1B/MODY5 genes, and the genotypic frequency of NEUROD1 variations were compared between the 96 MODY probands and 100 non-diabetic control subjects. A de novo modeling method was used to predict the three-dimensional (3D) structures of wild type (WT) and mutated NEUROD1 proteins. Transcriptional activities of both WT and mutant of NEUROD1 on insulin gene were detected by using dual luciferase reporter gene system. Results ·Glu59Gln (NM_002500.5, c.175G>C), a heterozygous missense mutation in the NEUROD1 gene, was identified in a MODY pedigree. 3D structural analysis showed that the mutation transformed the negatively charged Glu59 of WT into uncharged mutation Gln59, leading to the loss of Glu59-Arg54 and Glu59-Lys88, two salt bridge bonds, and the formation of Gln59-Arg54, one new hydrogen bond. Transcriptional activity of Glu59Gln mutant for insulin gene was reduced by 36.3% when compared with that of WT (P<0.05). A common variation Ala45Thr (G-A) was identified, and AA+GA genotypic frequency of the variation was significantly elevated in the 96 MODY probands in comparison to non-diabetic control subjects (P=0.002). Conclusion ·Glu59Gln mutation alters the N-terminal molecular conformation of NEUROD1 protein, resulting in decreased transcriptional activity of insulin gene, which is the cause of the defective insulin secretion in mutation carriers of the MODY6 pedigree. The Ala45Thr variation is associated with earlier age of onset of diabetes in MODY6 probands.

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Clinical significance of FEV_0.5 and FEV_0.75 in the determination of pulmonary function in children with bronchial asthma

ZHENG Guimei, TANG Lanfang

2023, 43 (10): 1262-1267.
doi: 10.3969/j.issn.1674-8115.2023.10.006

Abstract ( 229 )

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Objective ·To evaluate the abnormal rates of measured/predicted values of forced expiratory volume in 0.5 second (FEV_0.5) and FEV_0.75 in lung ventilation function testing, as well as the clinical significance of different cut-off points for improvement rates before and after bronchodilation testing in the diagnosis of children with bronchial asthma (asthma). Methods ·From January 2020 to February 2021, school-age children diagnosed with asthma during their hospitalization at the Children's Hospital, Zhejiang University School of Medicine were selected. The data on lung ventilation function testing and bronchodilator testing were collected. The difference in abnormal rates of measured/predicted values of FEV_t in children in lung ventilation function testing was compared. Diagnostic test four grid table was used to analyze the sensitivity and specificity of different cut-off points for the improvement rates of FEV_0.5 and FEV_0.75 in the diagnosis of asthma before and after bronchodilation testing. Results ·A total of 148 children were included. All enrolled cases completed lung ventilation function testing, with 51 cases completing bronchodilation testing simultaneously. The results of lung ventilation function testing showed that 21 patients had obstructive ventilation dysfunction, 30 patients had small airway dysfunction, and the remaining patients had normal, restrictive or mixed ventilation dysfunction. The results of bronchodilation testing showed that in the 51 asthmatic children with obstructive ventilation dysfunction and small airway dysfunction, 22 of them were positive for bronchodilation testing. The comparison of the abnormal rates of FEV_t measured/predicted values showed that the abnormal rates of FEV_0.75 measured/predicted values were higher than those of FEV₁ and FEV_0.5 (χ²=10.18, P=0.000; χ²=10.95, P=0.000). The sensitivity and specificity analysis results of different cut-off points for the improvement rates of EFV_0.75 and FEV_0.5 showed that the cut-off point for FEV_0.5 improvement rate at 16% had very high sensitivity and specificity, with the highest Jordan index; the cut-off points for FEV_0.75 improvement rate were 12% and 14%, respectively, with sensitivity and specificity reaching 100%. Conclusion ·The measured/predicted value of FEV_0.75 in lung ventilation function testing can be considered as an alternative indicator for the measured/predicted value of FEV₁ to further evaluate the presence of obstructive ventilation dysfunction. On the basis of the results of bronchodilation testing, it can be considered to analyze the airway reversibility by combining the best cut-off points of FEV_0.75 and FEV_0.5 improvement rates, in order to enhance the clinical value of bronchodilation testing in the diagnosis of asthma.

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Analysis of early efficacy and safety of endovascular therapy for acute mild ischemic stroke with large vessel occlusion

NI Ruilong, ZHAO Fei, CAO Li, DENG Jiangshan

2023, 43 (10): 1268-1273.
doi: 10.3969/j.issn.1674-8115.2023.10.007

Abstract ( 210 )

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Objective ·To investigate the early efficiency and safety of endovascular therapy (EVT) for patients with acute mild ischemic stroke with large vessel occlusion (LVO-MIS). Methods ·A total of 31 patients with LVO-MIS who received emergency EVT-assisted standard medical treatment at the Green Channel of Stroke in Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine from June 2016 to October 2022 were retrospectively included as endovascular therapy group (EVT group), and 32 LVO-MIS patients who only received standard medical treatment in the same period were selected as the control group. General clinical data and parameters related to EVT of the two groups were collected. The primary outcome was early efficacy, that is, the NIHSS at seventh day after treatment (d7NIHSS) score decreased by ≥3 points or directly to 0 points from baseline NIHSS score. Secondary outcomes included successful revascularization of blood vessels and early neurological deterioration (END), and safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. The primary and secondary outcomes of the two groups of patients were analyzed to evaluate the early efficiency of EVT, and the safety evaluation indicators of the two groups of patients were analyzed to evaluate the safety of EVT. Kruskal-Wallis H test was used to analyze the NIHSS scores of 24 patients in the EVT group who underwent EVT before and after treatment. Results ·There was no statistically significant difference in the general clinical data between the two groups, as well as parameters related to EVT such as occlusion site, and onset-to-admission time. The baseline NIHSS score of the EVT group [5.0 (3.0, 5.0) points] was higher than that of the control group [3.5 (2.0, 5.0) points] (P=0.001), and their d7NIHSS score [1.0 (0, 3.0) points] was lower than that of the control group [2.0 (1.0, 5.8) points] (P=0.040). A total of 24 patients (38.1%) in the two groups achieved early efficacy, including 16 cases in the EVT group and 8 cases in the control group; and the early efficacy rate of the EVT group was higher than that of the control group (χ²=4.729, P=0.030). The END rate in the EVT group was lower than that in the control group (χ² =6.097, P=0.014), and there were 29 cases (93.5%) in the EVT group of patients whose blood vessels were successfully reopened. There was no statistically significant difference in sICH rate and mortality rate between the two groups. In the EVT group, there was a statistically significant difference (H=16.997, P=0.000) among the baseline NIHSS scores [5.0 (3.0, 5.0) points] of 24 patients, postoperative 24hNIHSS score [2.0 (0.3, 3.8) points] and d7NIHSS scores [1.0 (0, 2.8) points]. Conclusion ·EVT is safe and effective in treating LVO-MIS, and the early efficacy rate of EVT is superior to standard medicine treatment, with a lower rate of END and no increased risk of sICH.

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Efficacy of sternal cortical thickness ratio in adult chest CT in the diagnosis of osteopenia and osteoporosis

YU Xi, SUN Junnan, ZHANG Jiaojiao, GAO Yue, WANG Hu, YU Yang, WANG Hairong, HONG Wen

2023, 43 (10): 1274-1281.
doi: 10.3969/j.issn.1674-8115.2023.10.008

Abstract ( 159 )

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Objective ·To compare the relationship between sternal cortical thickness ratio and bone mineral density in adult emergency inpatients with chest CT plain scan, and evaluate the diagnostic ability of sternal cortical thickness ratio for osteopenia and osteoporosis. Methods ·The bone density was measured by dual energy X-ray absorptiometry (DXA) in hospitalized patients collected in the adult emergency ward of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from November 2020 to October 2022, and the patients were diagnosed as normal bone mass, osteopenia, or osteoporosis according to the bone density. The patients were grouped based on age (>65 years old, ≤65 years old) and osteoporosis status. The sternal cortical thickness ratio measured at the level of tracheal bifurcation in the chest CT scan image of each group was analyzed. Spearman correlation was used to analyze the correlation between the sternal cortical thickness ratio and bone mineral density. The sternal cortical thickness ratio was used to diagnose the osteopenia and the osteoporosis, and the receiver operator characteristic curve (ROC curve) was drawn to obtain the best cut-off value. The diagnostic efficacy of the sternal cortical thickness ratio in the diagnosis of osteopenia and osteoporosis was analyzed. Results ·A total of 198 patients were included in the study, including 78 patients with normal bone mass, 66 patients with osteopenia, and 54 patients with osteoporosis. Among patients aged >65 years old (n=115), the proportion of female patients and the age of patients in the osteoporosis group were significantly higher than those in the normal bone mass group (all P<0.05). However, in patients ≤65 years old (n=83), the difference was not statistically significant (P>0.05). Whether in patients >65 years old or ≤65 years old, the sternal cortical thickness ratio in the normal bone mass group was higher than that in the osteopenia group and the osteoporosis group, and the sternal cortical thickness ratio in the osteopenia group was higher than that in the osteoporosis group (all P<0.05); The sternal cortical thickness ratio in female patients in the normal bone mass group, osteopenia group and osteoporosis group was lower than that in male patients (all P<0.05). The sternal cortical thickness ratio in both male and female patients was positively correlated with bone mineral density (r=0.704, P=0.000; r=0.785, P=0.000; r=0.735, P=0.000; r=0.479, P=0.000). In terms of diagnostic performance, in patients >65 years old, the diagnostic accuracy rate of male patients in the normal bone mass group was higher than that in the osteopenia group and the osteoporosis group, and the diagnosis misdiagnosis rate in the osteoporosis group was lower than that in the normal bone mass group and the osteopenia group; In patients ≤65 years old, the diagnostic accuracy rate of male patients in the osteoporosis group was higher than that in the normal bone mass group and the osteopenia group, and the diagnosis misdiagnosis rate in the normal bone mass group was lower than that in the osteopenia group and the osteoporosis group. Conclusion ·The sternal cortical thickness ratio in both male and female patients is positively correlated with bone mineral density, and the sternal cortical thickness ratio has good diagnostic efficacy for osteopenia and osteoporosis.

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Clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma

ZHAO Jie, JIANG Yan, HAO Siguo

2023, 43 (10): 1282-1288.
doi: 10.3969/j.issn.1674-8115.2023.10.009

Abstract ( 313 )

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Objective ·To analyze the clinical characteristics and prognostic risk factors of patients with diffuse large B-cell lymphoma (DLBCL), and evaluate the prognostic effects of autologous stem cell transplantation (ASCT) and rituximab maintenance therapy on DLBCL patients. Methods ·The clinical data of 160 patients with DLBCL who were first diagnosed by pathology and immunotyping were collected from the Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from January 2015 to January 2020, and the risk factors affecting the efficacy and prognosis of patients were analyzed. Moreover, the clinical characteristics of patients with relapsed/refractory DLBCL and the effect of salvage ASCT on overall survival (OS) were assessed. For those high-risk patients who achieved complete remission (CR) in the interim assessment, the impact of ASCT and rituximab maintenance therapy on survival outcomes was further assessed. Results ·Patients with initial age of treatment >60 years (P=0.005), International Prognostic Index (IPI) 3?5 scores (P=0.032), low albumin level (P=0.001) and anemia (P=0.007) had poor efficacy. Multivariate analysis showed that the initial age of treatment >60 years (HR=2.788, 95%CI 1.575?4.936, P=0.000), non-GCB subtype (HR=2.230, 95%CI 1.150?4.324, P=0.018), elevated lactate dehydrogenase level (HR=2.064, 95%CI 1.006?4.234, P=0.048) and low albumin level (HR=2.052, 95% CI 1.169?3.602, P=0.012) were the independent risk factors for progression-free survival (PFS). The initial age of treatment >60 years (HR=2.269, 95% CI 1.060?4.860, P=0.035) and IPI scores of 3 to 5 (HR=2.557, 95%CI 1.132?5.778, P=0.024) were independent factors affecting OS. For patients with relapsed/refractory DLBCL, salvage ASCT was found to significantly improve the prognosis of these patients and was a protective factor for the death event of patients (P=0.030). For patients in the high-risk group who achieved CR in the interim evaluation after chemotherapy, there were no deaths in patients on maintenance therapy with consolidation ASCT and rituximab to the end point of follow-up; however, it did not prolong the OS of the patients (P>0.05). Conclusion ·In patients with relapsed/refractory DLBCL, salvage ASCT can significantly prolong the OS, whereas in the high-risk patients of DLBCL, consolidation ASCT and rituximab maintenance therapy can't prolong the OS.

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Expert consensus on postoperative rehabilitation nursing of patients with head and neck cancer

GU Fen, WANG Yueping, YANG Wenyu, ZHAO Xiaomei, TANG Yan, SHEN Shukun, MAO Yan, ZHANG Jinfeng, WU Yifan, ZHANG Yuanyuan, YANG Yue, ZHANG Jianchun, YU Hong, WANG Lan, HAO Guihua, HOU Lili

2023, 43 (10): 1289-1296.
doi: 10.3969/j.issn.1674-8115.2023.10.010

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The location and size of tumors, treatment methods and prognosis of patients with head and neck cancer can seriously affect their oral function and neck activity, thereby affecting daily activities such as eating, speech and upper limb movement. Early rehabilitation after head and neck cancer surgery can accelerate functional recovery, alleviate discomfort symptoms, improve quality of life, and reduce unnecessary rehabilitation or treatment measures. Developing a clinical rehabilitation nursing pathway for head and neck cancer, forming personalized rehabilitation plans, and conducting early and effective nursing interventions are currently one of the key points of clinical work for patients with head and neck cancer. At present, domestic and foreign guidelines or consensus pays less attention to the impairments of speech function, chewing and swallowing function, neck and shoulder function etc., and lacks a systematic and comprehensive rehabilitation nursing guide or consensus to provide practical guidance for the care of patients with head and neck cancer. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine organized relevant experts from Beijing, Shanghai, Sichuan, Shaanxi, Zhejiang and Anhui to draft Expert consensus on postoperative rehabilitation nursing of patients with head and neck cancer basing on previous literature and clinical nursing skills and experiences, of which the aim is to provide guidance for those patients in the aspects of oral care, nutritional support, flap donor area care, care after tracheotomy, chewing and swallowing rehabilitation, speech function rehabilitation, neck and shoulder function rehabilitation, restricted mouth opening rehabilitation, risk identification and prevention and follow-up.

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Research progress on the association between melatonin and hypertensive disorder complicating pregnancy

LU Ruoyu, KANG Wenhui, ZHAO Anda, LU Zhaohui, LI Shenghui

2023, 43 (10): 1297-1303.
doi: 10.3969/j.issn.1674-8115.2023.10.011

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Melatonin (N-acetyl-5-methoxytryptamine) is a polypotent neuroendocrine lipid-soluble small molecule secreted mainly by the pineal gland. During gestation, melatonin levels in the mother at night rise as the pregnancy progresses and return to normal after delivery. The etiology of hypertensive disorder complicating pregnancy (HDCP) is multifaceted. An increasing number of evidence suggests the involvement of melatonin in the pathogenic process, and the regulation is related to its expression level, secretion rhythm and receptor level. Abnormal placental blood circulation, ischemia and hypoxia and systemic vascular endothelium dysfunction are the main pathological processes of HDCP. Through direct antioxidant effect, melatonin improves mitochondrial dysfunction and protects trophoblast cells from oxidative damage, thus participating in the regulation of placental oxidative stress level, and plays a protective role in preventing oxidative damage caused by hypoxic ischemia reperfusion of placenta, thus maintaining placental functional homeostasis. In addition, there is also evidence that melatonin can protect maternal vascular endothelium from oxidative stress by reducing the production and secretion of pro-inflammatory cytokines and vasoactive compounds, and participating in the regulation of systemic blood pressure in pregnant women. These confidences suggest that melatonin can be involved in the maintenance of placental and systemic vascular functional homeostasis during pregnancy through the regulation of oxidative stress. In this article, the effects of melatonin on HDCP and the related mechanisms are reviewed, and the positive role of melatonin in the pathogenesis of HDCP is summarized.

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Research progress on the neural circuit of pain emotion mediated by amygdala

MA CUI, YE Yujuan, YAN Xingke

2023, 43 (10): 1304-1310.
doi: 10.3969/j.issn.1674-8115.2023.10.012

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The occurrence of pain emotion is closely related to the functional and structural changes of specific central nervous circuit. When pain is accompanied by depression, anxiety, pain aversion memory and other emotional states, it activates or inhibits different neural circuits. The amygdala (AMY) of the limbic system participates in the regulation of pain, anxiety, depression, aversive memory and other emotions, and has extensive connections with brain nuclei related to pain and emotion, jointly regulating pain, anxiety, depression, aversive memory and other responses. This article summarizes the main circuits related to pain emotions mediated by AMY. It is concluded that the neural circuits related to depression include central amygdala → parafascicular nucleus of thalamus (CeA ^GABA → PF ^Glu), dorsal raphe nucleus → central amygdala (DRN ^5-HT → CeA ^SOM), central amygdala → ventrolateral periaqueductal gray (CeA ^GABA → vlPAG ^GABA). Nerve circuits related to anxiety include ventral tegmental area → central amygdala (VTA→CeA^DA), locus coeruleus → basolateral amygdala (LC^NE→BLA). The neural circuit related to pain aversion memory is lateral parabrachial nucleus → central amygdala (lPBN ^CGRP→CeA ^CGRP). Among them, activating the CeA^GABA→PF ^Glu circuit can lead to depression accompanied by pain, activating the CeA ^GABA→vlPAG ^GABA circuit can alleviate pain sensitivity caused by depression, and activating the DRN ^5-HT→CeA ^SOM circuit can alleviate pain perception and depressive emotions; activating the VTA→CeA ^DA loop can alleviate pain sensitivity and anxiety like behavior, inhibiting LC ^NE→BLA loop can alleviate anxiety caused by pain; activating the lPBN ^CGRP→CeA ^CGRP loop can generate pain aversion memory.

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Review of role of fatty acid binding protein-4 in obesity-associated tumors

WU Ruifang, FENG Ming, MENG Jian

2023, 43 (10): 1311-1316.
doi: 10.3969/j.issn.1674-8115.2023.10.013

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Obesity is one of the major factors threatening human health. Excessive fat accumulation not only has detrimental effects on human metabolism and cardiovascular system, but also is highly correlated to the incidence and mortality of various tumors. Fatty acid binding protein-4 (FABP4) is a small molecule protein mainly expressed in adipocytes and macrophages, and is responsible for participating in fatty acid transport and lipid response. It has been found that FABP4 levels are not only associated with body fat content, but also aberrantly expressed in various obesity-associated tumor cells and tumor microenvironment, which is closely related to obesity-associated carcinogenesis, metastasis, recurrence and patient prognosis. Since FABP4 expression varies in different types of obesity-associated tumors, suggesting a complex role of FABP4 in tumorigenesis. Based on this, this article reviews different roles of FABP4 in multiple obesity-associated tumors.

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Research progress of MDSCs-targeted immunotherapy for pancreatic cancer

QIN Yahan, ZHANG Ke, ZHANG Mengyu, SHEN Jie, PENG Meiyu

2023, 43 (10): 1317-1323.
doi: 10.3969/j.issn.1674-8115.2023.10.014

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Pancreatic cancer (PC) is a highly malignant digestive system tumor with a poor survival rate and prognosis. Most patients with pancreatic cancer have no obvious clinical manifestations in the early stage of the disease, and are found to be in the middle and late stage of the disease when they seek treatment.A unique and complex tumor microenvironment (TME) is formed during its development and evolution. Due to the occult nature of pancreatic cancer, for patients with advanced pancreatic cancer, some traditional treatment methods such as surgical resection and chemotherapy are very limited, and there is a lack of effective treatment programs. Of course, this is also related to the immunosuppression of the TME of pancreatic cancer. Some immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), play an important immunosuppressive role in helping tumor immune escape. Therefore, it is considered to be a major difficulty in the treatment of pancreatic cancer. In recent years, with the in-depth study of TME, immunotherapy has gradually become a new therapeutic strategy, and has made great progress in the treatment of various malignant tumors. The study found that targeted MDSCs therapy is a new and effective treatment for pancreatic cancer.In this paper, we introduce the role of MDSCs in TME and their progress as potential targets for immunotherapy of pancreatic cancer, hoping to provide new directions for the treatment of pancreatic cancer and other tumors.

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Recent advance in autophagy-related pathways and key biomarkers in major depressive disorder

LI Siyuan, HE Shen, LI Huafang

2023, 43 (10): 1324-1331.
doi: 10.3969/j.issn.1674-8115.2023.10.015

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Major depressive disorder (MDD) is a very common and severe mental disorder. Persistent emotional distress is one of its main clinical symptoms. The etiology of MDD is complex and highly heterogeneous, and has not yet been clarified. Antidepressant is a kind of important method for the treatment of MDD. However, there are still some problems such as slow onset of effect, low cure rate, safety to be further improved, and low compliance, which also reflect people's lack of understanding of the pathogenesis of MDD. Autophagy is a mechanism of cell degradation, which plays an important role in maintaining the stabilization of homeostasis. Mammalian target of rapamycin (mTOR) is an important regulator of autophagy, and adverse conditions can activate autophagy through mTOR-dependent or mTOR-independent autophagy pathways. Microtubule-associated protein light chain 3-Ⅱ (LC3-Ⅱ), Bcl-2 interacting coiled-coil protein 1 (Beclin-1) and p62 are common to be used in the measurement of autophagy flux. In recent years, more and more studies have shown that impaired autophagy may be involved in the development of MDD and antidepressant treatment may affect autophagy. Therefore, regulating impaired autophagy pathways may be a promising target of antidepressant treatment. In the future, more attention should be paid to the study of autophagy signaling pathway in the central nervous system to provide more reliable evidence for the mechanism of MDD and antidepressant treatment. This article introduces the roles of common mTOR-dependent autophagy pathways, mTOR-independent autophagy pathways and autophagic markers in the progression and treatment of MDD.

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Advances in preoperative medical management of metabolic surgery

SHAN Yingyi, YU Haoyong

2023, 43 (10): 1332-1338.
doi: 10.3969/j.issn.1674-8115.2023.10.016

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Obesity is a chronic metabolic disease that is increasing in prevalence and has become a major public health problem and epidemic in many countries, including China. Obesity and its associated complications, such as type 2 diabetes (T2DM), non-alcoholic fatty liver disease, hypertension, and cardiovascular disease, seriously damage health. With the continuous development of metabolic surgery, it has become a widely used, safe and effective method for treating obesity and its associated complications. Metabolic surgery can significantly lose weight, improve metabolic indicators, reduce the risk of chronic diseases such as diabetes and hypertension, improve the quality of life of patients, and bring comprehensive health benefits to patients. However, there is currently a lack of standardized preoperative medical management for metabolic surgery, which may lead to metabolic disorders, nutrient deficiencies, and other complications, increasing the risk of surgery and postoperative complications, and affecting the efficacy of weight loss and the prognosis of patients. Through the systematic review of literature related to preoperative weight loss, glycemic control, blood pressure and lipid control, micronutrient supplementation, and psychological and behavioral modifications, this paper reviews preoperative medical management of metabolic surgery with the aim of providing reference for effectively improving the safety and efficacy of metabolic surgery and improving the prognosis of patients.

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