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    Innovative research team achievement column
    Gene expression program analysis of cancer-testis genes
    HOU Zongliang, YANG Qin, LI Shaobai, LEI Ming
    2023, 43 (8):  945-954. 
    doi: 10.3969/j.issn.1674-8115.2023.08.001

    Abstract ( 128 )   HTML ( 31 )   PDF (5222KB) ( 71 )  

    Objective ·To identify the gene expression program (GEP) of cancer-testis genes (CTGs) during spermatogenesis based on single-cell transcriptome data from the testis and investigate their association with the prognosis of cancer patients. Methods ·Expression profiles of normal and tumor tissues were obtained from the GTEx and TCGA databases to screen CTGs. The GEP of CTGs during spermatogenesis was identified by applying the leiden clustering algorithm to testicular single-cell transcriptome data. DecoupleR was used to evaluate the activity levels of GEP and determine the cell types and stages of spermatogenesis where each GEP was active. Subsequently, DecoupleR was used to evaluate the activity levels of GEP in tumor tissues and analyze the correlation between GEP and cancer patient survival. Results ·Based on the expression profiles of normal and tumor tissues from the GTEx and TCGA databases, 917 CTGs were identified. By using the expression patterns of CTGs in the testicular single-cell transcriptome data, seven GEPs were identified through the clustering algorithm. Activity level analysis revealed that GEP5 was active in the early stages of spermatogenesis, including spermatogonia stem cells, differentiating spermatogonia, and early primary spermatocytes. The distribution of GEP5-associated genes was predominantly found on the X chromosome. Additionally, survival analysis demonstrated a statistically significant negative correlation between GEP5 activity levels and patient survival in various tumors. Conclusion ·During spermatogenesis, GEP5 is active in early stages, and its associated genes are primarily located on the X chromosome. In multiple tumor types, the activity level of GEP5 is closely related to patient prognosis.

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    Psychological and behavioral cross effects for health
    Study on factors influencing social network service addiction among junior college students based on problem behavior theory
    WANG Suping, TANG Hua, ZHOU Dong, CAI Yong, GONG Ruijie
    2023, 43 (8):  955-962. 
    doi: 10.3969/j.issn.1674-8115.2023.08.002

    Abstract ( 142 )   HTML ( 30 )   PDF (1846KB) ( 112 )  

    Objective ·To construct a structural equation model based on problem behavior theory to conduct a study on social network addiction among junior college students. Methods ·A cross-sectional questionnaire survey was conducted in a college in Shanghai. Logistic regression analysis was used to analyze the effects of gender, grade, study pressure, self-esteem, loneliness, depression, entrapment, defeat, interpersonal needs, perceived social support, smoking, alcohol, exercise, and academic achievement on social network service addiction. Based on the problem behavior theory, the structural equation model was used to construct a theoretical framework model of social network service addiction of junior college students. Results ·60.31% of the total 980 participants had social network service addiction. The univariate Logistic regression results showed that depression, self-esteem, loneliness, frustration, drowsiness, social support, interpersonal needs, exercise, and academic performance had a significant impact on social network addiction. The structural equation model fitted well [S-Bχ2/df=8.03, goodness-of-fit index (GFI)=0.924, comparative fit index (CFI)=0.909, Tucker-Lewis index (TLI)=0.872, root mean square error of approximation (RMSEA)=0.096, standardized root mean square residual (SRMR)=0.070], suggesting the mutual influence between the personality system and the perceived environment system, between the personality system and the behavioral system, and between the perceived environment system and the behavior system interact (β=1.018, P=0.000; β=0.218, P=0.003; β=0.268, P=0.000). The influence of personality system and behavior system on social network service addiction was not statistically significant, while the perceived environment system had a significant positive impact on social network service addiction (β=0.481, P=0.001). Conclusion ·Personality system and behavior system indirectly affect social network service addiction by influencing perceived environment system, and perceived environment system directly affects social network service addiction. For the problem of social network addiction among lower grade college students, it is necessary to fully respect the characteristics of college students, and work together from three levels of the system to reduce the risk of social network addiction among college students.

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    A longitudinal study on new onset anxiety among children and adolescents during the COVID-19 epidemic
    WANG Xiaoyu, PENG Yinhui, MA Wenlin, YAO Boshuang, LI Yifan, ZHAO Li, YANG Chunxia
    2023, 43 (8):  963-970. 
    doi: 10.3969/j.issn.1674-8115.2023.08.003

    Abstract ( 127 )   HTML ( 27 )   PDF (1369KB) ( 51 )  

    Objective ·To investigate the occurrence of new onset anxiety symptoms in children and adolescents during the COVID-19 epidemic, and analyze the influencing factors. Methods ·Based on Chengdu Positive Child Development (CPCD) cohort, a total of 5 566 children and adolescents from five primary and secondary schools in Chengdu were enrolled. Two longitudinal study cohorts of new anxiety symptoms in children and adolescents were established, and two rounds of survey were conducted. The first round of survey (baseline survey) was conducted from December 2019 to January 2020, and the general demographic characteristics of the cohort members were collected through the Student Questionnaire for the Study on Promoting Positive Growth of Children and Adolescents. The second round of survey (follow-up survey) was conducted from February to July 2020 to collect additional information on the cohorts' infection history of COVID-19, and whether their eating, learning, and social and recreational activities were affected by the COVID-19 epidemic. The Screen for Child Anxiety Related Emotional Disorders (SCARED) was used to evaluate the new onset anxiety symptoms of all subjects. The multivariate Logistic regression model was used to analyze the influencing factors of new onset anxiety symptoms in children and adolescents. Results ·The results of SCARED assessment showed that the incidence of new onset anxiety symptoms among children and adolescents in Chengdu during the COVID-19 epidemic was 13.47%. In the longitudinal study cohort of new onset anxiety in children,the incidence was 11.91%, and in the longitudinal study cohort of new onset anxiety in adolescents, the incidence was 14.25%. The results of chi square test showed that there were statistically significant differences in the incidence of new onset anxiety symptoms among children in terms of age, whether they or their family members were infected with COVID-19, and whether their eating, learning and social activities were affected (all P<0.05); there were also statistically significant differences in the incidence of new onset anxiety symptoms among adolescents in gender, grade, age, residential area, and whether their eating, learning, and social and recreational activities were affected (all P<0.05). The results of multivariate Logistic regression analysis showed that, for children, 6?8 years old was the protective factor for their new onset anxiety symptoms, while they or their family members infected with COVID-19 and the impact of their learning activities were the risk factors (all P<0.05); for adolescents, males, residing in urban areas, and grades ≤ 6 were the protective factors for their new onset anxiety symptoms, while the impact of their learning activities was the risk factor (all P<0.05). Conclusion ·For children and adolescents, the factors that affect their new onset anxiety symptoms during the COVID-19 epidemic are not completely the same. For children, age, whether they or their family members are infected with COVID-19, and whether their learning is affected are independent influencing factors; but for adolescents, gender, grade, residential area, and whether their learning is affected are independent influencing factors. Therefore, in the process of dynamically paying attention to the mental health status of children and adolescents and continuously doing a good job of mental health intervention, it is necessary to follow the law of growth, fully consider the developmental characteristics of children and adolescents, and adopt different strategies and measures.

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    Relationship between egocentrism and non-suicidal self-injury in junior high school students
    MA Wenlin, LIN Yuanjie, JIN Tingting, SHI Wei, JIANG Lihua, ZHAO Li
    2023, 43 (8):  971-976. 
    doi: 10.3969/j.issn.1674-8115.2023.08.004

    Abstract ( 113 )   HTML ( 30 )   PDF (1576KB) ( 57 )  

    Objective ·To investigate the relationship between egocentrism and non-suicidal self-injury (NSSI) among junior high school students, with a focus on the mediating role of depression symptoms. Methods ·Data were collected from the Chengdu Positive Youth Development Cohort from June to July 2020, with a sample of 3 014 junior high school students. The Chinese Adolescent Egocentrism Scale (CAES), Deliberate Self-Harm Inventory (DSHI), and Center for Epidemiological Studies Depression Scale for Children (CES-DC) were used for on-site questionnaires. The survey data were entered, organized, and analyzed by using SPSS 23.0 software. Multiple regression analysis was used to analyze the relationship between egocentrism and NSSI in junior middle school students, and the mediating effect of depressive symptoms was examined by deviation-corrected non-parametric percentile Bootstrap method. Results ·Egocentrism was significantly positively correlated with depression symptoms and NSSI. Egocentrism was significantly positively correlated with depression symptoms (r=0.15, P=0.000), depression symptoms were significantly positively correlated with NSSI (r=0.48, P=0.000), and egocentrism was positively correlated with NSSI (r=0.14, P=0.000 ). Egocentrism significantly predicted NSSI (R2=0.06, P=0.000). Within egocentrism, self-conceitedness significantly positively predicted NSSI with a regression coefficient of R2=0.05, while disregarding others significantly negatively predicted NSSI with R2=0.01. Depression symptoms have a significant positive predictive effect on NSSI, R2=0.25. Depression symptoms are observed to partially mediate the relationship between egocentrism and NSSI. The direct effect value of egocentrism on NSSI was 0.20 (95%CI 0.06?0.34, P=0.000). The indirect effect value of egocentrism on NSSI via depression symptoms was 0.29 (95%CI 0.04?0.10, P=0.000). The mediating effect of depression symptoms accounted for 59.18% of the total effect value. Conclusion ·Lowering levels of self-conceitedness and increasing the tendency to disregard others within junior high school students' egocentrism will mitigate the risk of NSSI. Prevention efforts targeting NSSI among junior high school students should focus on individuals displaying depression symptoms.

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    Basic research
    Effects of PRPS1 I72 mutations on drug resistance in acute lymphoblastic leukemia and its mechanisms
    CUI Zhiyan, CHEN Yao, TAO Yue, SHEN Shuhong, LI Hui
    2023, 43 (8):  977-987. 
    doi: 10.3969/j.issn.1674-8115.2023.08.005

    Abstract ( 94 )   HTML ( 21 )   PDF (3278KB) ( 69 )  

    Objective ·To study whether mutations at the I72 site of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) can induce resistance in acute lymphoblastic leukemia (ALL) cells to thiopurine chemotherapy drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), and explain their mechanisms of action. Methods ·The PRPS1 gene mutations (I72F, R177S and V316L) found in clinical practice and PRPS1 gene mutations (V208A and V289A) present in two ALL cell lines (KOPN72bi and RS4;11) were constructed into the vector pGV303 fused with green fluorescent protein (GFP), respectively. The PRPS1 A190T mutation that has been proven to be resistant to thiopurine chemotherapy drugs was used as the positive control, and the empty vector pGV303 (Vector), PRPS1 wild-type (WT) and PRPS1 I72V were used as the negative controls. The various mutants of PRPS1 were transiently transfected into HEK-293T cells (referred to as 293T cells), and the expression of these exogenous PRPS1 was detected by Western blotting. The half maximal inhibitory concentration (IC50) of 6-MP or 6-TG on the above 293T cell lines transiently transfected with PRPS1 mutants was detected and calculated by drug sensitivity experiments. Subsequently, in addition to PRPS1 I72F and I72V, multiple mutations I72M, I72L, I72N, I72S and I72T were constructed into the vector pGV303, respectively, by changing the isoleucine (I) at position 72 into other amino acids. The various mutants were transiently transfected into 293T cells, respectively, and the protein expression of each mutant and IC50 values of 6-MP or 6-TG were detected by Western blotting and drug sensitivity experiments. PRPS1 WT, I72F, I72V, A190T and pGV303 vectors were transfected into REH cell lines by lentivirus infection, and GFP-positive cells were sorted by flow cytometry to obtain cells with stable expression of PRPS1 mutants. The protein expression of each mutant in REH cells and IC50 values of 6-MP or 6-TG were detected by Western blotting and drug sensitivity experiments to verify the results of drug sensitivity experiments obtained by 293T cells. Annexin V/DAPI double staining was used to evaluate the apoptosis of each REH cell line, and Western blotting was used to detect the levels of DNA damage-related proteins [phosphorylation at S139 of histone H2AX (phosphorylated H2AX-S139, γ-H2AX), phosphorylated check point kinase 2 (pCHK2)], and apoptosis-related protein cleaved poly (ADP-ribose) polymerase (cleaved PARP) in each REH cell line. The diagrams of amino acid residues and spatial conformations of I72 locus, I72V and I72F were predicted and drawn through three-dimensional imaging and PyMOL software by using the crystal structure data of PRPS1-numbered 2HCR (PDB code 2HCR) in the PDB (Protein Data Bank) database. Results ·Western blotting results showed that the transiently transfected exogenous PRPS1-mutated proteins were successfully expressed in 293T cells. The drug sensitivity experiment results showed that the IC50 values of 6-MP or 6-TG in 293T cells expressing PRPS1 I72F, R177S, V316L, V208A and the positive control A190T were much higher than those in cells expressing V289A and the negative control Vector, PRPS1 WT and I72V (all P =0.000). After mutating the isoleucine (I) at position 72 with other amino acids, Western blotting results showed successful expression of exogenous PRPS1-mutated proteins at position I72 after transient transfection in 293T cells. Drug sensitivity experiments revealed the IC50 values of 6-MP or 6-TG in 293T cells expressing PRPS1 I72M, I72F, I72L, I72N, I72S, I72T and positive control A190T were much higher than those in cells expressing negative control Vector, PRPS1 WT and I72V (all P=0.000). Western blotting results showed that the protein expression levels of PRPS1 WT, A190T, I72F and I72V in the REH stable cell lines constructed by lentivirus were high and similar. The drug sensitivity experiment results showed that the IC50 values of 6-MP or 6-TG in REH cells expressing PRPS1 I72F and positive control A190T were much higher than those in cells expressing negative control Vector, PRPS1 WT and I72V (all P=0.000), which was consistent with the drug sensitivity results obtained by transient transfection in 293T cells. The results of Annexin V/DAPI double staining method and the detection of DNA damage and apoptosis-related proteins by Western blotting showed that after 6-MP treatment, the DNA damage and apoptosis rates of REH cell lines expressing PRPS1 A190T and I72F were significantly lower than those of cells expressing negative control Vector, PRPS1 WT and I72V (all P=0.000). The protein structure analysis results showed that PRPS1 I72F could change the conformation of PRPS1. Conclusion ·The PRPS1 I72F, R177S, V316L, V208A, I72M, I72L, I72N, I72S and I72T mutations can confer drug resistance to the thiopurine chemotherapy drugs in cells, while the PRPS1 V289A and I72V mutations do not affect cell sensitivity to the thiopurine chemotherapy drugs. The drug sensitivity experiment results in 293T cells are consistent with those in REH cells, demonstrating that 293T cells can serve as a rapid research model for detecting the resistance of PRPS1 mutations to thiopurine chemotherapy drugs. The effects of the PRPS1 I72 mutations on the resistance of the thiopurine chemotherapy drugs may be related to changes in the structure of PRPS1.

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    Translocator protein activates autophagy in diabetic neuropathic pain rats via regulation of the Keap1/Nrf2/HO-1 signaling
    GAO Nan, HAO Gem, MA Bingjie, JIN Tian, MA Ke, LIU Xiaoming
    2023, 43 (8):  988-996. 
    doi: 10.3969/j.issn.1674-8115.2023.08.006

    Abstract ( 94 )   HTML ( 22 )   PDF (3810KB) ( 46 )  

    Objective ·To study the effects of translocator protein (TSPO) agonist Ro5-4864 on autophagy and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-derived-2-like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in diabetic neuropathic pain (DNP) rats. Methods ·Type 2 diabetic rats were established by high-fat diet and streptozotocin (STZ), and DNP rats were filtered by behavioral assessment. Twenty-four rats were randomly assigned to the Sham group, DNP group, TSPO agonist Ro5-4864 group (Ro group), and TSPO agonist Ro5-4864 combined with Nrf2 inhibitor ML385 group (Ro+ML385 group). Up-Down method was used to measure paw 50% mechanical withdrawal threshold (50% PMWT) of the rats before high-fat diet (baseline), and on Day 3, 7, 14, 21 and 28 after STZ. Sciatic nerves were collected on the last day to analyze the effects of Ro5-4864 on autophagy related proteins and Keap1/Nrf2/HO-1 signaling related proteins of DNP rats by using immunofluorescence and Western blotting. Results ·The 50% PMWT in the DNP group decreased from D3 to D28 (P=0.000 at all timing), and the expression of Bcl-2 interacting coiled-coil protein 1 (Beclin-1), microtubule-associated protein light chain 3-Ⅱ (LC3-Ⅱ), HO-1, and nuclear Nrf2 (P=0.000) were significantly reduced in the sciatic nerves of DNP rats (all P=0.000), compared with those in the sham group, but p62 was significantly increased (P=0.000). Administration of Ro5-4864 attenuated these changes in the rats of the Ro group. There was a gradual increase in the 50% PMWT, compared with that of the rats in the DNP group (D14 P=0.039, both D21 and D28 P=0.000), and the impairment of autophagy and the Keap1/Nrf2/HO-1 signaling was repaired, which was demonstrated by increases of Beclin-1, LC3-Ⅱ, HO-1, and nuclear Nrf2 protein contents (all P=0.000) and a decrease in p62 content (P=0.001). However, the beneficial effects of Ro5-4864 were totally abrogated by ML385 in rats of the Ro+ML385 group. Conclusion ·TSPO alleviates DNP in rats, of which the mechanism involves activation of autophagy via upregulation of the Keap1/Nrf2/HO-1 signaling in sciatic nerves. This study provides a new strategy for the treatment of DNP.

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    Effect of rhubarb on gut microbiota-host co-metabolism in rats
    GAO Yu, YIN Shan, PANG Yue, LIANG Wenyi, LIU Yumin
    2023, 43 (8):  997-1007. 
    doi: 10.3969/j.issn.1674-8115.2023.08.007

    Abstract ( 88 )   HTML ( 18 )   PDF (2519KB) ( 40 )  

    Objective ·To study the effect of rhubarb administration on the balance between intestinal flora and the body. Methods ·Wistar rats were randomly divided into 4 groups (n=8), which were given extractions of rhubarb 0.1 g/kg (low dose group), 2.5 g/kg (medium dose group), 4.5 g/kg (high dose group) and normal saline (control group) by intragastric administration for 5 d, and the daily change of fecal water content of rats was observed. Gas chromatography/time of flight mass spectrometry (GC/TOFMS) approach was used to detect the metabolites in serum, colon tissue and fecal of rats on the 5th day of administration. Principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) were used to analyze the differences of metabolites between different dose groups and the control group. The metabolites with statistical significance were obtained by t-test. Results ·The water content of rat feces in the dose group gradually increased with the time and dose after rhubarb administration. Compared with the control group, 28, 18 and 20 differential metabolites were obtained in serum, colon tissue and fecal samples from different dose groups, which showed significant changes (P<0.05) on the 5th day. At the same time, the levels of 17 serum metabolites, 2 colon tissue metabolites, and 10 fecal metabolites altered significantly in a dose-dependent manner. Among these differential metabolites, some gut microbial-host co-metabolites, including neurotransmitters, indoles, and bile acids, were observed to alter significantly after rhubarb administration. The levels of fecal catechol and indole-3-acetic acid increased while the levels of fecal phenylalanine, 4-aminobutyric acid, L-DOPA, and indole-3-propionic acid decreased. Deoxycholic acid level was significantly elevated in colon tissue samples from the high-dose group. Compared with the control group, phenylalanine, tyrosine, and tryptophan levels in serum samples also increased in different dose groups. In addition, the levels of fumaric acid (one of organic acids related to energy metabolism), was down-regulated in fecal samples but up-regulated in colon tissue and serum samples. With the increase of dosage, the level of glutamic acid (one of amino acids) significantly increased in serum samples but gradually decreased in colon tissue samples. Except for 6-phosphogluconic acid, the levels of carbohydrates and lipid metabolites, including fructose, pyruvate, lactic acid, glucose-1-phosphate, D-glycero-1-phosphate docosenic acid, 13-docosenoic acid, 1-monostearoylglycerol, and cholesterol increased in the serum samples, while those of D-glycero-1-phosphate in colon tissue and lactic acid, glucose-1-phosphate, and linolenic acid in fecal samples decreased. Conclusion ·Rhubarb affects brain-gut axis and bile acid metabolism through the gut microbial-host co-metabolism, and further affects the body's energy metabolism, amino acid metabolism, glycometabolism and lipid metabolism.

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    SIRT2 regulates macrophage chemotaxis by de-modifying histone H4K8 lactylation
    SONG Wenting, TAO Yue, PAN Yi, MO Xi, CAO Qing
    2023, 43 (8):  1008-1016. 
    doi: 10.3969/j.issn.1674-8115.2023.08.008

    Abstract ( 250 )   HTML ( 35 )   PDF (4083KB) ( 168 )  

    Objective ·To explore the regulatory role of silent information regulator 2 (SIRT2) in modulating the immune phenotype of macrophages after infection by removing the lactylation at H4K8 site of histone and the corresponding mechanism. Methods ·Human THP-1 leukemia cells were induced by phorbol 12-myristate 13-acetate (PMA) and stimulated by lipopolysaccharide (LPS) to establish a macrophage infection model. Macrophages without LPS treatment (pTHP-1) were set as the control (CTRL) group, and macrophages with LPS treatment were set as the infected (LPS) group. Western blotting was used to detect the level of histone modification and SIRT2 protein in macrophages. RT-qPCR was used to detect the expression level of glycolytic key enzymes [phosphofructokinase liver type (PFKL), lactate dehydrogenase A (LDHA)] and modulators genes hypoxia inducible factor 1α (HIF-1α), and the expression level of Sirtuin genes and HDAC genes between the two groups. Transwell was used to detect the ability of macrophage chemotaxis. Lentivirus packaging and cell infection were used to construct SIRT2 overexpression cell line. The interaction analysis method of RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) was used to analyze the difference and pathway enrichment of the genes specifically bound to H4K8 lactylation (H4K8la). Results ·Compared to the CTRL group, macrophage glycolysis was upregulated and the level of H4K8la was significantly increased in the LPS group (P<0.05), while the level of lactylation in other sites remained unchanged. Among all known enzymes with deacetylation modification function, only SIRT2 showed a significant decrease after LPS treatment (P<0.05), and overexpression of SIRT2 could significantly inhibit the level of H4K8la modification, while the level of H4K8ac remained unchanged (P>0.05). The interactive analysis of ChIP-seq and RNA-seq revealed that chemotaxis-related genes were regulated by H4K8la, and macrophage chemotaxis ability significantly decreased after the overexpression of SIRT2 and downregulation of H4K8la (P<0.05). Conclusion ·SIRT2 can change the expression of target genes related to chemotaxis by removing H4K8la modification, thereby reducing the chemotaxis ability of macrophages. Targeting SIRT2 and H4K8la modification may help control inflammation mediated by macrophages.

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    Clinical research
    Analysis of the effect of anti-tuberculosis treatment and lung injury in patients with tuberculosis combined with underlying disease
    LUO Mengxing, ZOU Xin, GAO Yaxian, WU Xiaocui, YU Fangyou, HU Yang, ZENG Qibing, LIU Zhonghua
    2023, 43 (8):  1017-1023. 
    doi: 10.3969/j.issn.1674-8115.2023.08.009

    Abstract ( 95 )   HTML ( 24 )   PDF (1551KB) ( 44 )  

    Objective ·To investigate the impact of complications on the prognosis and lung injury of patients with tuberculosis.. Methods ·A retrospective cohort study was used for analysis, to select a total of 450 smear-positive tuberculosis (TB) patients, 323 males (71.8%) and 127 females (28.2%), from January to December 2018 at Shanghai Pulmonary Hospital, Tongji University School of Medicine, which were divided into non-complication group and complication group (diabetes, hypertension, liver diseases, kidney diseases and gallbladder diseases). Overall treatment outcomes and lung injuries in TB patients with and without complications were analyzed by using χ2 test. Stratified analysis of the impact of each comorbidity on the prognosis and lung injury of TB patients was performed. Kaplan-Meier analysis was used to analyze the temporal correlation between complications and tuberculosis prognosis. Results ·Four hundred and fifty patients with a median age of 33 years were included, 173 of whom had complications: diabetes in 49 cases, hypertension in 23 cases, liver diseases in 83 cases, kidney diseases in 35 cases, and gallbladder diseases in 17 cases. The cure rate of TB patients without complications was 80.5%, which was significantly higher than that of the group with complications (P<0.05); the significantly lower cure rate of TB patients with diabetes, hypertension and kidney diseases at diagnosis was the key cause of anti-tuberculosis treatment failure; TB patients with diabetes and liver diseases had higher lung bacterial load and larger areas of lung damage, and TB patients with diabetes and kidney diseases had higher incidence of pulmonary cavity. Conclusion ·Diabetes, hypertension and kidney diseases exacerbate lung damage and lead to lower TB cure rates. Early interventions by clinicians at the time of diagnosis can improve cure rates, shorten treatment time, and reduce medical costs for TB patients.

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    A study of the effect of suboptimal glycemic control on subclinical myocardial systolic function in patients with T2DM
    WU Lingheng, CHEN Jianxiong, ZHANG Mengjiao, SHA Lei, CAO Mengmeng, SHEN Cuiqin, DU Lianfang, LI Zhaojun
    2023, 43 (8):  1024-1031. 
    doi: 10.3969/j.issn.1674-8115.2023.08.010

    Abstract ( 96 )   HTML ( 19 )   PDF (2310KB) ( 43 )  

    Objective ·To explore the relationship between poor blood glucose control and early impaired cardiac function in patients with type 2 diabetes mellitus (T2DM). Methods ·Eighty-three patients diagnosed with T2DM in Jiading Branch of Shanghai General Hospital from June 2021 to March 2022 were selected and divided into two groups according to the level of hemoglobin A1c (HbA1c): satisfactory control of glycaemia (SCG) group and less satisfactory control of glycaemia (LSCG) group. Fifty-four subjects were in the control group. Echocardiography was performed to obtain left ventricular structural and functional parameters and left ventricular subendocardial, medial and subepicardial global longitudinal strain (GLS): GLSendo, GLSmid, and GLSepi. The parameters were compared by using analysis of variance. The correlation analysis was performed by Pearson correlation analysis and multiple linear regression analysis. The diagnostic performance of longitudinal strain in differentiating subclinical myocardial dysfunction in patients with T2DM was analyzed by receiver operator characteristic (ROC) curve. Results ·The thickness of the ventricular septum and the posterior wall of the left ventricle were thicker in the LSCG group than in the SCG group and the control group (all P<0.05), but there was no significant difference between the SCG and the control group (all P>0.05). Compared with the control group, the left ventricular diastolic function index E/e (early peak flow velocity by Doppler/early and atrial diastolic velocity of the mitral annulus by tissue Doppler imaging) was higher in both the LSCG group and the SCG group (all P <0.05), but there was no significant difference between the LSCG group and SCG group (P>0.05). There was no significant difference in left ventricular ejection fraction among the three groups (P>0.05). Compared with LSCG group, GLSendo, GLSmid and GLSepi were higher in the SCG group and control group (all P<0.05), but there was no significant difference between the SCG group and control group (P>0.05). HbA1c was an independently negative factor of GLSmid and GLSepi (β= -0.198 and -0.239, all P<0.05). GLSendo, GLSmid and GLSepi had moderate diagnostic performance between the LSCG group and SCG group, with areas under the curve (AUC) of 0.754 (95%CI 0.624?0.884), 0.755 (95%CI 0.624?0.885), and 0.751 (95%CI 0.619?0.882), respectively. Conclusions ·T2DM patients with unsatisfactory glycemic control have reduced myocardial contractility, and this subclinical myocardial damage is independently negatively correlated with the level of HbA1c.

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    Study on ultrasound-guided thyroid fine needle puncture assisted by rapid on-side evaluation
    HE Yujie, FAN Linrui, ZHANG Qiaochu, ZHANG Zhili, DING Jun, SHI Chao, YAO Yongqiang, REN Hongzheng
    2023, 43 (8):  1032-1037. 
    doi: 10.3969/j.issn.1674-8115.2023.08.011

    Abstract ( 122 )   HTML ( 21 )   PDF (857KB) ( 36 )  

    Objective ·To explore the clinical effect of ultrasound-guided fine needle aspiration cytology assisted by rapid on-side evaluation (ROSE). Methods ·The data of patients with thyroid nodules diagnosed in Gongli Hospital of Shanghai Pudong New Area from January 2019 to December 2022 were retrospectively analyzed (n=874). According to cytological detection methods, they were divided into ROSE+thinprep cytologic test (TCT) group (n=469) and cell smear (CS)+TCT group (n=405). In the ROSE+TCT group, the tissue and cell samples of ROSE were detected by Diff-Quik staining and continue puncturing until the specimen was satisfied. In the CS+TCT group, the tissue and cell samples were detected by hematoxylin-eosin staining (H-E staining) + Pap staining. Cytologic diagnosis was made according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) cytologic classification criteria, and the cell dissatisfaction rates and clinical outcomes of the 2 methods were compared. Results ·The dissatisfaction rates of the ROSE+TCT group and CS+TCT group were 2.4% and 14.1%, respectively, with statistical significance (P=0.000). The smear cells of the ROSE+TCT group were concentrated, and the structure was clear and easy to observe. The samples with a cytologic diagnosis of grade Ⅲ and above were prepared as cell wax blocks to improve the efficiency of subsequent diagnosis. The cells of the CS+TCT group could not produce wax blocks due to the small numbers of cells. The puncture times of the ROSE+TCT group were significantly different from that of the CS+TCT group (P=0.011). Conclusion ·The ultrasound-guided thyroid fine needle aspiration assisted by rapid on-site assessment method can assess the effective number of cells in the specimen on the spot, give feedback to the puncturing doctors on the spot, meet the diagnostic accuracy requirements of pathologists by collecting a sufficient number of cells, reduce the number of punctures and treatment time, and play a good auxiliary role in the diagnosis and follow-up examination of clinicians.

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    Review
    Research progress in visual fatigue related to stereoscopic video display terminals
    LIU Lu, KE Bilian
    2023, 43 (8):  1038-1043. 
    doi: 10.3969/j.issn.1674-8115.2023.08.012

    Abstract ( 121 )   HTML ( 22 )   PDF (1281KB) ( 75 )  

    In recent years, with the development of science and technology, stereoscopic video display terminals have become more and more widely used in many fields. Meanwhile, their influence on the eyes and even the whole body has gradually attracted people's attention. Most stereoscopic video display terminals are based on the principle of binocular parallax. They present image pairs with parallax for the left and right eyes respectively, and form stereoscopic images after brain fusion. At present, most studies about the influence of stereoscopic video display terminals on the physiological function of human eyes describe the changes of a certain type of ocular indicators independently, in which changes in visual functions, such as accommodation and convergence ability, tear film and ocular surface functions are particularly important. The appearance of related visual fatigue symptoms may be due to accommodation-vergence conflicts, excessive and rapid parallax changes, excessive retinal spatial frequencies, stereoscopic image distortion, and improper use environment. This paper introduces the principle of stereoscopic display, summarizes related symptoms and changes in visual functions, and discusses the causes of visual discomfort, in order to provide some bases for the healthy use of stereoscopic video display terminals and the clinical diagnosis and treatment of related symptoms.

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    Research progress in the role of gut microbiota in the pathogenesis and treatment of IgA nephropathy
    LI Junru, OUYANG Yan, XIE Jingyuan
    2023, 43 (8):  1044-1048. 
    doi: 10.3969/j.issn.1674-8115.2023.08.013

    Abstract ( 203 )   HTML ( 33 )   PDF (1212KB) ( 103 )  

    As the most common form of glomerulonephritis worldwide, IgA nephropathy (IgAN) is characterized by the diffuse deposition of immune complexes formed by glycosylation-deficient IgA1 (Gd-IgA1) and its specific antibodies (Gd-IgA1-IgG) in the glomerular mesangium. Although the mechanisms of Gd-IgA1 production are still unknown, there is accumulating evidence that Gd-IgA1-producing plasma cells are primarily derived from gut-associated lymphoid tissue, giving rise to the "gut-kidney axis" theory. Further research has discovered that gut microbiota may be involved in IgAN development and progression, and that several interventions to regulate gut microbiota, such as probiotics, fecal microbiota transplantation, and intestinal immunity modulation, may be used in the treatment of IgAN. In patients with IgAN, targeted-release formulation-budesonide has been shown to reduce urinary protein levels and delay kidney progression. Gut microbiota has promising potential as a preventive, diagnostic and therapeutic target for IgAN, and further research is needed.

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    Research progress in neuroimmune disorders in atopic dermatitis
    XUAN Zhenquan, CHEN Xuanyi, YAO Zhirong
    2023, 43 (8):  1049-1055. 
    doi: 10.3969/j.issn.1674-8115.2023.08.014

    Abstract ( 136 )   HTML ( 24 )   PDF (1227KB) ( 138 )  

    Atopic dermatitis (AD) is a chronic inflammatory skin disease with the highest incidence in the world. The main clinical manifestations are eczema-like skin lesions, pruritus and xeroderma. Recent studies have revealed that sensory neurons in the skin lesions of AD patients can interact abnormally with keratinocytes (KC) and immune cells, leading to neuroimmune disorders. Among them, there are two types of sensory neurons involved in neuroimmune disorders, including histaminergic and non-histaminergic sensory neurons. In neuroimmune disorders, KC and immune cells activate sensory neurons to induce pruritus by secreting proinflammatory cytokines such as interleukin-4 (IL-4), IL-13, IL-31, IL-33, and thymic stromal lymphopoietin, as well as chemokines such as C-X-C motif chemokine ligand 12 (CXCL12) and CXCL10. In addition, neuropeptides such as nerve growth factor, brain-derived neurotrophic factor and artemin secreted by KC and immune cells can induce overgrowth of sensory neurons, thereby promoting neuroimmune disorders. At the same time, the excessive release of neuropeptides such as calcitonin gene-related peptide and substance P by sensory neurons can act on KC and immune cells, thereby aggravating skin inflammation. In recent years, many drugs targeting neuroimmune disorders are in preclinical studies, clinical trials and other stages, or have been marketed for the treatment of AD. Among them, our research group has found that lidocaine, a local anesthetic, can target neuroimmune disorders and relieve pruritus and skin inflammation in AD patients. At present, the role of neuroimmune disorders in AD has not been systematically discussed. Based on this, this article reviews the types of sensory neurons involved in neuroimmune disorders, the role of KC, immune cells and sensory neurons in neuroimmune disorders, as well as the therapeutic strategies targeting neuroimmune disorders.

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    Research progress of the role of non-canonical Wnt signaling pathway in ovarian cancer and its potential therapeutic implications
    ZHOU Wanzhen, TENG Yincheng
    2023, 43 (8):  1056-1063. 
    doi: 10.3969/j.issn.1674-8115.2023.08.015

    Abstract ( 133 )   HTML ( 25 )   PDF (1663KB) ( 73 )  

    Ovarian cancer is a malignant tumor of the female reproductive system with the highest mortality, and involves the aberrant regulation of multiple molecular signaling pathways. As a highly conserved molecular pathway, Wnt signaling pathway plays an important role in embryonic development, tissue homeostasis, and tumorigenesis. Wnt signaling pathway includes canonical Wnt/β-catenin pathway and non-canonical pathway, and the latter mainly includes Wnt/planar cell polarity (Wnt/PCP) pathway and Wnt/Ca2+ pathway. Previous studies have mainly focused on the relationship between the canonical Wnt pathway and tumor progression. Recently, the non-canonical Wnt pathway has gradually received attention, and related researches have enriched the understanding of the non-canonical Wnt pathway in physiological and pathological processes such as tissue development and tumorigenesis. The existing studies suggest that the nonclassical Wnt pathway is abnormally regulated in ovarian cancer and is closely related to the staging and prognosis of ovarian cancer. Non-classical Wnt pathway plays an important role in many biological processes such as proliferation, migration and invasion of ovarian cancer cells, and the changes of this pathway are also related to chemotherapy resistance of ovarian cancer. This article reviews the role of the non-canonical Wnt pathway in ovarian cancer, and discusses the research progress of targeted therapy based on the non-canonical Wnt pathway, aiming to provide new ideas for the development of novel targeted drugs.

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    Review of CD4+ T cell subsets in asthma phenotypes: molecular mechanisms and biologic treatment options
    ZHAO Yanhong, WANG Chuanping
    2023, 43 (8):  1064-1070. 
    doi: 10.3969/j.issn.1674-8115.2023.08.016

    Abstract ( 98 )   HTML ( 19 )   PDF (1368KB) ( 69 )  

    Asthma is a chronic inflammatory airway disease, mainly driven by different CD4+ T cell subsets [helper T cell (Th cell)]. CD4+ T cell subsets are a type of important immune cells, capable of secreting various cytokines, and regulating the immune response of the body to various antigens. According to the difference of secreted cytokines, CD4+ T cell subsets can be divided into subgroups such as Th1, Th2, Th17, follicular helper T cell (Tfh) and regulatory T cell (Treg), which play different roles in the occurrence and development of asthma. Biologic therapy is a new treatment method that targets specific molecules and pathways, and has provided more options for asthma patients. Biologics is a type of drugs prepared by biotechnology, which can specifically recognize and neutralize target molecules, thereby interfering with related signaling pathways. This article reviews the roles and molecular mechanisms of various CD4+ T cell subsets in asthma phenotypes, summarizes the immunopathological characteristics of eosinophilic asthma, neutrophilic asthma and mixed asthma, the clinical efficacy and safety of biologics targeting Th2, Th1, Th17, Tfh and Treg cell-related factors, and the selection and development direction of corresponding biologics. This article also discusses the role of impaired Treg cells and abnormal dendritic cells (DC cells) in the pathogenesis of asthma, as well as the potential of immunotherapy using these cells. This article aims to provide reference for the personalized selection and new drug development of biologic therapy for asthma.

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