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28 November 2020, Volume 40 Issue 11 Previous Issue    Next Issue
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Innovative research team achievement
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Innovative research team achievement

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Study the regulatory role of STAT3 on CD8+ T cells using adoptive transfer model in immunodeficient mice ZENG Qun-xiong1, 2, DENG Jun1, 2, SHEN Nan1, 2 2020, 40 (11):  1437-1446.  doi: 10.3969/j.issn.1674-8115.2020.11.001 Abstract ( 1287 )   PDF (9750KB) ( 320 )   Objective · To investigate the intrinsically regulatory role of transcription factor STAT3 on the activation and proliferation of CD8+ T cells in immunodeficient Rag1-/- mice. Methods · The CD8+CD44-CD62L+Na?ve T cells, from CD45.1 wild type (WT) mice and CD45.2-CD8 (ΔStat3) mice, were sorted by flow cytometry cell sorter, equally mixed and labelled with Carboxyl Fluorescein diacetate Succinimidyl Ester (CFSE), and then transferred (i.v.) to the Rag1-/- mice. Ten days after CD8+ T cells transfer, the proportion and proliferation of CD8+ T cells in the spleen, mesenteric lymph nodes (mLNs) and popliteal lymph nodes (pLNs) were determined by flow cytometry. TNF-α, IFN-γ, FasL and granzyme B (GraB) produced by the CD8+ T cells were measured with flow cytometry after PMA and ionomycin stimulation. The statistical significance of activation and effectors expressed between WT and ΔStat3 CD8+ T cell was analyzed by t test. Results · The percentages of WT CD8+ T cells in spleen, mLNs and pLNs were significantly higher than that in ΔStat3 CD8+ T cells (76.2% vs 23.4%, 82.1% vs 17.4%, 64.5% vs 32.3%, with all P=0.008). The percentage and cell number of activated CD44+CD8+ T cells in WT CD8+ T cells were much higher than those in ΔStat3 CD8+ T cells in pLNs (all P=0.008). In spleen, pLNs and mLNs, the levels of TNF-α, IFN-γ, GraB and CD107a expressed in WT CD8+ T cells were higher than those in ΔStat3 CD8+ T cells (all P<0.05). Conclusion · Rag1-/- mice can work as an ideal model to evaluate the survival, proliferation, activation and function of CD8+ T cells in vivo. STAT3 intrinsically regulates the proliferation, activation and function of CD8+ T cells in vivo. Related Articles | Metrics

Original article (Basic research)

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Effects of silenced Ttf1 on genes expression of Kiss1 and GnRH in neuronal cells and arcuate nucleus of female rats ZANG Shao-lian, YIN Xiao-qin, LÜ Yong-fen, XU Li-ya, GUO Sheng, LI Pin 2020, 40 (11):  1447-1453.  doi: 10.3969/j.issn.1674-8115.2020.11.002 Abstract ( 682 )   PDF (8337KB) ( 267 )   Objective · To explore the effects of inhibiting thyroid transcription factor 1 (Ttf1) expression on Kiss1 and gonadotropin-releasing hormone (GnRH) expressions in neuronal cells and hypothalamic arcuate nucleus (ARC) of female rats. Methods · Three shRNAs (TTF1-shRNA1, TTF1-shRNA2, and TTF1-shRNA3) interference sequences were designed for rat Ttf1 gene and were constructed into lentiviral vectors. The efficiency of LV-TTF1-shRNA was detected by real-time PCR and Western blotting in neuronal cell line ND7-23. And the expressions of Kiss1 and GnRH were tested 72 h after transfection. Moreover, LV-TTF1-shRNA or the blank lentiviral vector was injected into 21-day female rats’ ARC. Kiss1 and GnRH expressions were detected at the juvenile (25-day), early puberty (35-day) and adult (42-day) stages. Meanwhile, vaginal opening time of the rats was recorded. Results · Seventy-two hours after lentivirus transfection in ND7-23 cells, the mRNA and protein expressions of Ttf1 decreased significantly in LV-TTF1-shRNA2 group and LV-TTF1-shRNA3 group (all P<0.05), particularly in LV-TTF1-shRNA3 group. The expressions of Kiss1 and GnRH mRNA reduced significantly after LV-TTF1-shRNA3 being transfected in ND7-23 cells (both P<0.05). After injection of LV-TTF1-shRNA3 in female rats’ ARC, mRNA abundance of Kiss1 and GnRH showed evident reduction at 25-day, 35-day and 42-day stages (all P<0.05). And KISS1 protein reduced significantly at 35-day and 42-day stages. Female rats transfected with LV-TTF1-shRNA3 showed delayed vaginal opening. Conclusion · Inhibition of Ttf1 gene expression not only significantly reduces the expression of Kiss1 and GnRH in neuronal cells and female rats’ ARC, but also causes female rats vaginal opening delay. Related Articles | Metrics

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Effects of different rewarming rates on neuron autophagy in the cardiac arrest/resuscitation rat model treated with hypothermia LI Yi, HU Yue, SUN Da-wei, CUI De-rong 2020, 40 (11):  1454-1460.  doi: 10.3969/j.issn.1674-8115.2020.11.003 Abstract ( 605 )   PDF (9373KB) ( 263 )   Objective · To investigate the effects of different rewarming rates on neuron autophagy in the rats with therapeutic hypothermia following cardiac arrest and cardiopulmonary resuscitation. Methods · The SD rats were randomized into 4 groups, i.e., sham operation group (Sham group), normothermia group (Normo group), slow rewarming group (SR group) and fast rewarming group (FR group). Except Sham group, the other three groups were given cardiopulmonary resuscitation after the establishment of 5-min asphyxial cardiac arrest model. The rats in Normo group were maintained at (37.0±0.5) ℃ ; SR group and FR group were treated with hypothermia (34 ℃ ) for 4 h, and SR group was rewarmed at 0.5 ℃ /h and FR group was rewarmed at 4 ℃ /h to (37.0±0.5) ℃ . SR+chloroquine group and FR+chloroquine group were isolated from the two rewarming groups, and the rats in these two groups were injected intraperitoneally with chloroquine 10 mg/kg 1 h before operation. Morphological changes of cortical motor neurons were detected by Nissl staining. The expressions of autophagy- and lysosomal-related proteins at corresponding time points, i.e., microtubule-associated protein 1 light chain 3- Ⅱ (LC3- Ⅱ ), lysosome-associated membrane protein 2 (LAMP2), P62, Bcl 2-interacting protein-1 (Beclin1), cathepsin D, and ubiquitin, were examined by Western blotting and immunofluorescence. Results · The expressions of LC3- Ⅱ and Beclin1 increased significantly in SR group 6 h after hypothermia treatment compared to Normo group (both P=0.000). Compared with SR group, FR group showed an obviously lower number of viable cortical neurons (P=0.000), significantly decreased expressions of LAMP2 and cathepsin D (both P=0.000), and increased expressions of ubiquitin (P=0.007) and P62 (P=0.000). Compared with SR group, the expressions of ubiquitin (P=0.000) and P62 (P=0.001) in SR+chloroquine group increased, while the expressions of ubiquitin (P=0.000) and P62 (P=0.007) decreased in FR+chloroquine group compared with FR group. Conclusion · Fast rewarming after therapeutic hypothermia for cardiac arrest and cardiopulmonary resuscitation can lead to neuron lysosomal dysfunction, impaired autophagy flux, and increased neuronal damage; however, slow rewarming activates autophagy and reduces neuronal injury. Related Articles | Metrics

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Detection of activity of mutant protein in ALG3-CDG LUO Bing-jie, LI Sheng-tao, WANG Ning, GAO Xiao-dong 2020, 40 (11):  1461-1467.  doi: 10.3969/j.issn.1674-8115.2020.11.004 Abstract ( 809 )   PDF (8680KB) ( 295 )   Objective · To investigate the activity detection method of α-1,3-mannosyltransferase (ALG3) mutant protein in congenital disorder of glycosylation (ALG3-CDG), and examine the relationship between the activity and the severity of disease. Methods · The mutation sites of the patients in the reports were I69T, W71R, G96R, M157K, R171Q and M209T, respectively. After homologous alignment of the amino acid sequences of Homo sapiens and Saccharomyces cerevisiae (S. cerevisiae) ALG3, six yeast mutant proteins (I70T, Y72R, G98R, L157K, R171Q and M221T) related to ALG3-CDG were designed. These mutants were expressed in Escherichia coli (E. coli). Using E. coli membrane containing wild-type ALG3 or its mutant proteins as catalysts, the relative activities of mutant proteins were calculated by liquid chromatography tandem mass spectrometry based on the catalytic activity of wild type protein. The activities of corresponding mutations in the patients with different survival time were compared. Results · Six ALG3-CDG related S. cerevisiae conserved ALG3 mutant proteins were expressed in E. coli in the comparable protein expression levels with wild type ALG3. The in vitro quantitative activity assay of enzymes showed that compared with the wild type ALG3, the relative activities of the mutant proteins I70T, Y72R, G98R, L157K, R171Q and M221T were 2.8%, 4.9%, 4.5%, 17.2%, 4.8% and 22.3%, respectively. The corresponding mutation activity was significantly higher in the patients with survival longer than 1 year than that in the patients with survival less than 1 year (P=0.002). Conclusion · An in vitro quantitative method is established to measure the enzymatic activities of ALG3-CDG related S. cerevisiae ALG3 mutants, providing the possibility to predict the severity of ALG3-CDG. Related Articles | Metrics

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Effect of surgical trauma on postoperative cognitive function and cerebral glucose metabolism in type 2 diabetic mice LUO Gang, CUI Yong-chen, CAO Yue, ZHANG Jun-feng 2020, 40 (11):  1468-1472.  doi: 10.3969/j.issn.1674-8115.2020.11.005 Abstract ( 588 )   PDF (7010KB) ( 200 )   Objective · To observe the changes of learning and memory functions and as well as the changes of the glucose metabolism in the corresponding functional brain regions in type 2 diabetic mice after abdominal surgery. Methods · Forty 5-week-old male mice of C57BL/6 wild-type, which were fed on 60% high-fat diet, and the type 2 diabetes models were established with nicotinamide and streptozocin 4 weeks later. These mice were then randomly divided into control group (n=15) and abdominal surgery group (surgery group, n=15). The open field experiment and the fear conditioning experiment were performed to assess the learning and memory functions in each group (n=10). Positron emission tomography/computed tomography (PET/CT) was used to measure the uptake of 18F-fluorodeoxyglucose (18F-FDG) in different brain regions of mice in each group (n=5). Results · In the open field experiment, there was no significant difference in the number of central grid crossings and total movement distance between the control group and the surgery group. In the fear conditioning experiment, the freezing time ratios of the surgery group in the contextual test and the tone-related test were lower than those in the control group (both P<0.05). The standard intake rates of 18F-FDG in hippocampus, cerebral cortex, striatum and amygdala in the surgery group were significantly higher than those of the control group (all P<0.05). Conclusion · Postoperative cognitive dysfunction after abdominal surgery in type 2 diabetic mice may be associated with the abnormal cerebral glucose metabolism in relevant cerebral areas. Related Articles | Metrics

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Determination of half-life and half-lethal dose of itaconic acid in C57BL/6J male mice GUO Yang-yang1, 2, LEI He-hua2, WANG Yu-lan3 2020, 40 (11):  1473-1476.  doi: 10.3969/j.issn.1674-8115.2020.11.006 Abstract ( 704 )   PDF (3995KB) ( 264 )   Objective · To determine the half-life and half-lethal dose of itaconic acid in mice, and provide intuitive data for the metabolic rate and toxicity of itaconic acid in mice. Methods · Itaconic acid was injected into mice through caudal vein. The concentration of itaconic acid was measured by blood collection under fundus venous plexus at different time. At the same time, the survival of the mice was recorded after injection for 14 d. Results · Under the conditions of this experiment, the half-life of itaconic acid in male C57BL/6J mice was 29.13 min, and the half-lethal dose of is 258.263 mg/kg. Conclusion · Itaconic acid has a fast metabolic rate and a short half-life in mice. Itaconic acid is less toxic, based on its half-lethal dose in mice. Related Articles | Metrics

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Prediction and bioinformatics analysis of hsa-miR-223-3p target genes related to diabetes mellitus YU Meng-na1, YANG Biao2, YANG Li-zhen1 2020, 40 (11):  1477-1484.  doi: 10.3969/j.issn.1674-8115.2020.11.007 Abstract ( 785 )   PDF (12978KB) ( 286 )   Objective · To analyze target genes of human miR-223-3p (hsa-miR-223-3p) and their biological processes, and explore biomarkers related to diabetes mellitus (DM). Methods · starBase database was used to screen hsa-miR-223-3p target genes, and Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genome (KEGG) and Reactome pathway analysis were performed. Hub genes were obtained by constructing protein-protein interaction (PPI) network, and the most significant modules were screened out. The hub genes related to DM were analyzed by Venn diagram. Results · A total of 870 hsa-miR-223-3p target genes were screened out. The GO enrichment analysis, KEGG and Reactome pathway analysis showed that the target genes were mainly related to the regulation of RNA polymerase Ⅱ promoter, cell response to insulin stimulation, RNA binding, etc, and were mainly enriched in insulin secretion, ubiquitin-mediated proteolysis and estrogen-dependent gene expression. There were 31 hub genes in PPI network, and hub gene PRKACB participated in insulin secretion pathway. Top 3 modules were identified as follows: module 1 was involved in ubiquitin-mediated proteolysis, module 2 was involved in RNA transport and cell cycle, and module 3 was involved in endocytosis. Conclusion · Hsa-miR-223-3p may participate in a variety of biological processes through target genes, and the hub gene PRKACB may provide assistance for exploring the pathogenesis of DM. Related Articles | Metrics

Original article (Clinical research)

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Establishment of the reference intervals of serum anti-Müllerian hormone in healthy women of childbearing age in Shanghai WU Chen-yu1, LU Yu-wei1, HUANG Yi-jie1, ZHU Chen-feng2, QIN Heng-wei1, WU Xin-rui1, WU Jia-hao3#, ZHANG Jian2# 2020, 40 (11):  1485-1488.  doi: 10.3969/j.issn.1674-8115.2020.11.008 Abstract ( 694 )   PDF (6043KB) ( 404 )   Objective · To establish the reference intervals of serum anti-Müllerian hormone (AMH) in healthy women of childbearing age in different age groups in Shanghai. Methods · A total of 239 healthy women of childbearing age, who accepted staff physical examination in International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, during July 2019, were enrolled and detected for serum AMH level using chemiluminescence immunoassay. After the outlier exclusion, 234 subjects were finally included and divided into six age groups. The reference intervals of serum AMH in healthy women of childbearing age in different age groups in Shanghai were established. The natural logarithm of serum AMH level and age were fitted by quadratic regression model. Results · The reference interval of serum AMH level was expressed as M(P5–P95), which were 4.76 (0.96–14.17) ng/mL in women aged 19–24 years, 6.03 (1.38–16.56) ng/mL in women aged 25–29 years, 4.30 (0.95–10.73) ng/mL in women aged 30–34 years, 2.40 (0.33–9.27) ng/mL in women aged 35–39 years, 1.04 (0.05–4.00) ng/mL in women aged 40–44 years, and 0.21 (0.01–3.04) ng/mL in women aged 45–49 years. After logarithmic transformation, serum AMH level and age could well obey the quadratic regression model (R2=0.502). Conclusion · The reference intervals of serum AMH level established for the first time in healthy women of child-bearing age in Shanghai may provide the basis for the evaluation of ovarian reserve function of women of different ages. Related Articles | Metrics

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Clinical effect of periodontal initial therapy on peritoneal dialysis patients with periodontitis LU Wei-li1, ZHANG Xu-yun1, LIAO Yue1, CHEN Hui-wen1, LIU Ying-li2, SONG Zhong-chen1 2020, 40 (11):  1489-1494.  doi: 10.3969/j.issn.1674-8115.2020.11.009 Abstract ( 656 )   PDF (8496KB) ( 241 )   Objective · To investigate the clinical effect of periodontal initial therapy on uremic peritoneal dialysis patients with chronic periodontitis. Methods · Thirty-three uremic patients with chronic periodontitis who were treated with peritoneal dialysis in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine and Huashan Hospital, Fudan University were included. They were randomly divided into experimental group (16 cases, receiving both periodontal initial therapy and peritoneal dialysis treatment) and control group (17 cases, receiving peritoneal dialysis treatment). The periodontal clinical indexes including plaque index (PLI), bleeding index (BI), probing depth (PD) and clinical attachment loss (CAL), and laboratory indexes including parathyroidhormone (PTH), serum creatinine (Scr), C-reactive protein (CRP), red blood cell (RBC), blood glucose and hemoglobin (Hb) of the two groups were detected before and after treatment. The differences of the above indexes between groups and within groups were statistically analyzed. Results · Compared with baseline before treatment, the periodontal clinical indexes of the experimental group were improved at 3 months after treatment (all P<0.05), and the laboratory indexes Scr and CRP were also improved (both P<0.05). Pearson correlation analysis showed that there was a correlation between periodontal clinical indexes and laboratory indexes in uremic peritoneal dialysis patients with periodontitis. Conclusion · Periodontal initial therapy can improve the periodontal and systemic symptoms in uremic peritoneal dialysis patients with chronic periodontitis. Related Articles | Metrics

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A clinical research of ED90 norepinephrine to prevent hypotension after combined spinal and epidural anesthesia during cesarean delivery SHEN Ting, XU Tao, ZHENG Jing, AN Xiao-hu, XU Zi-feng, CHAI Jing 2020, 40 (11):  1495-1499.  doi: 10.3969/j.issn.1674-8115.2020.11.010 Abstract ( 615 )   PDF (6791KB) ( 484 )   Objective · To determine the optimal intravenous norepinephrine bolus dose needed to prevent hypotension after combined spinal and epidural anesthesia in 90% of women during elective cesarean delivery. Methods · Forty women undergoing elective cesarean delivery were allocated into this double-blinded, prospective, and sequential dose-finding study using biased coin design sequential method. The primary outcome was the successful use of the norepinephrine bolus dose to maintain systolic blood pressure above 80% of the baseline until delivery. Secondary outcomes included dizziness, breathlessness, nausea, vomiting, bradycardia, secondary hypertension and supplemental use of atropine or norepinephrine of the women, as well as 1 min and 5 min Apgar scores of the newborns. The 90% effective dose (ED90) and its 95%CI were estimated using Isotonic regression methods. Results · The estimated ED90 intravenous bolus dose of norepinephrine was [10.85 (95%CI 9.20-11.67)] μg to prevent hypotension after combined spinal and epidural anesthesia during cesarean delivery. The occurrence rates of dizziness, breathlessness, and nausea were 2.5%, 7.5% and 10.0%, respectively. The occurrence rate of additional rescue norepinephrine boluses was 5.0%. No vomiting, bradycardia, secondary hypertension and supplemental use of atropine appeared. Apgar scores of all newborns at 1 min and 5 min were 10. Conclusion · An intravenous norepinephrine bolus dose of 11 μg is recommended to prevent hypotension after combined spinal and epidural anesthesia during cesarean delivery for clinical practice. Related Articles | Metrics

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Correlation analysis of lung cancer and anemia XU Shu-lin, WU Jing, LOU Jia-tao 2020, 40 (11):  1500-1504.  doi: 10.3969/j.issn.1674-8115.2020.11.011 Abstract ( 741 )   PDF (6146KB) ( 307 )   Objective · To analyze the correlation between basic information, clinicopathological characteristics, anti-tumor treatment options, prognosis and anemia in lung cancer patients. Methods · The clinical data and laboratory indexes of 246 patients with lung cancer from August 2013 to November 2014 were collected. According to the occurrence of anemia after the anti-tumor therapy, the patients were divided into anemia group and non-anemia group. And according to the survival time, they were divided into survival group and death group. Chi-square test, t test and rank sum test were used to compare the related factors of anemia and prognosis in different patient groups, and Spearman correlation coefficient was used to analyze the relationship between hemoglobin level and anemia-related factors in anemia group. Results · After anti-tumor therapy, 175 patients (71.1%) developed anemia, mainly mild anemia. Anti-tumor treatment with platinum-based chemoradiotherapy could easily cause anemia (P=0.000). There were significant differences between the anemia group and the non-anemia group in tumor stage, Performance Status score, secondary disease and serum albumin level (all P<0.05). And the hemoglobin level in anemia group was positively correlated with the serum albumin level (r=0.498, P=0.000). Compared with the death group, the levels of hemoglobin, serum albumin, serum iron and folic acid in the survival group were higher, and the levels of serum ferritin, glycosylated hemoglobin and lactate dehydrogenase in the survival group were lower (all P<0.05). Conclusion · The occurrence of anemia in lung cancer patients is affected by many factors, and is related to the prognosis. Therefore, the treatment of anemia should be given enough attention, and attention should be paid to individualized treatment. Related Articles | Metrics

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Study on portable dental irrigator for oral hygiene in patients with gingival inflammation SUN Wen-tao, WANG Yi-wei, QIAN Jie-lei, SUN Meng-jun, XIE Yu-feng, SHU Rong 2020, 40 (11):  1505-1508.  doi: 10.3969/j.issn.1674-8115.2020.11.012 Abstract ( 949 )   PDF (6439KB) ( 389 )   Objective · To compare the effect of traditional plaque control method (Bass method of tooth brushing) and the same method combined with portable dental irrigator on plaque control and gingival inflammation in adult gingivitis and mild chronic periodontitis patients, and explore the role of dental irrigator in oral health maintenance. Methods · Seventy-eight adult patients with gingivitis and mild chronic periodontitis were enrolled in this study. They were randomly divided into two groups, toothbrush (control group) and toothbrush combined with dental irrigator (experimental group). The plaque index (PLI), gingiva index (GI), bleeding index (BI) and plaque percentage were measured at baseline, after 2 weeks and 6 weeks respectively. Results · PLI, BI, GI and plaque percentage observed in the control group and experimental group were decreased after 2 weeks of continuous oral hygiene maintenance, compared with the baseline (all P<0.05). PLI, BI, GI and plaque percentage observed in the control group and experimental group were decreased after 6 weeks of continuous oral hygiene maintenance, compared with the baseline (all P<0.05). BIs of smooth surface and adjacent surface in the control group and experimental group after 2 weeks and 6 weeks were improved, compared with baseline, and the improvement of BI in the experimental group was significantly better than that in the control group (both P<0.05). Conclusion · Portable dental irrigator can assist patients to achieve better oral health during periodontal treatment and maintenance, and help them maintain periodontal health. Related Articles | Metrics

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Reliability and validity of Chinese version of Adolescent Reasons for Quitting Scale FENG Yong-hui, LI Hui, CHEN Meng-gui, CAI Xing-hua 2020, 40 (11):  1509-1514.  doi: 10.3969/j.issn.1674-8115.2020.11.013 Abstract ( 797 )   PDF (7715KB) ( 278 )   Objective · To introduce and localize the Adolescence Reasons for Quitting Scale (ARFQ) and test its reliability and validity. Methods · Convenient sampling was used. Three hundred and eighty-four high school students were selected as sample 1 for item analysis, exploratory factor analysis, discriminant validity test, internal consistency reliability and split-half reliability. One hundred and ninety-one high school students were selected as sample 2 for confirmatory factor analysis. Four weeks later, 60 students in sample 1 were selected for retest. Results · The Chinese version of ARFQ included 4 dimensions and 16 items. Four common factors extracted by exploratory factor analysis were named "Short-Term Consequences" "Long-Term Concerns" "Social Disapproval" and "Relatives' and Friends' Disapproval", and the cumulative variance contribution rate was 64.04%. Confirmatory factor analysis showed that four-factor model fitted well [χ2/df=2.06, root mean square error of approximation (RMSEA) =0.05, incremental fit index (IFI) =0.95, goodness of fit index (GFI) =0.94, adjusted goodness of fit index (AGFI) =0.91, and Tucker-Lewis index (TLI) =0.94]. The Cronbach's α coefficient of the scale was 0.79, and the coefficient of each dimension was 0.72-0.90. The split-half reliability was 0.76, and the test-retest reliability was 0.84. Conclusion · The Chinese version of ARFQ is a valid and reliable instrument to measure the motivation of adolescents' quitting smoking. Related Articles | Metrics

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Research progress of effect of antipsychotics on resting brain function in patients with schizophrenia WANG Ying-chan, WANG Ji-jun 2020, 40 (11):  1515-1518.  doi: 10.3969/j.issn.1674-8115.2020.11.014 Abstract ( 595 )   PDF (8000KB) ( 120 )   Antipsychotic drugs are the most commonly used treatment for schizophrenia. How antipsychotics affect brain function so as to improve clinical symptoms is still poorly understood. How brain works at rest reflects the inherent activity pattern of the brain in the resting state which is a foundation of all cognitive activities. To learn how antipsychotics affect brain function is helpful to understand the pathogenesis of mental illness and to seek better therapeutic targets. In this article, the changes of resting state brain area activities, brain network functional connectivities and the topology characteristics of whole brain functional network in the patients with schizophrenia before and after antipsychotic treatment are reviewed, and the future prospect is discussed. Related Articles | Metrics

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Research progress in the mechanism of ferroptosis and its role in liver related diseases HE Ming, WEI Qian, ZHANG Ying-ting 2020, 40 (11):  1519-1523.  doi: 10.3969/j.issn.1674-8115.2020.11.015 Abstract ( 977 )   PDF (8587KB) ( 499 )   Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation. Glutathione peroxidase 4 (GPX4) can prevent ferroptosis by converting lipid peroxides into nontoxic lipid alcohols under normal condition. However, recent studies have shown that ferroptosis in hepatocytes is one of the factors that induce and aggravate various liver diseases such as alcoholic fatty liver disease. Thereby, inducing ferroptosis of cancer cells by inhibiting GPX4 may be a new strategy for the treatment of liver cancer. This article reviews the molecular mechanism of ferroptosis and its role in liver related diseases, in order to provide new research directions and ideas for the treatment of liver diseases. Related Articles | Metrics

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Inducers and inhibitors of necroptosis and their research progress in diseases CAO Li-yuan, MU Wei 2020, 40 (11):  1524-1529.  doi: 10.3969/j.issn.1674-8115.2020.11.016 Abstract ( 856 )   PDF (8612KB) ( 316 )   As an important form of programmed cell death, necroptosis is getting more and more attention and has overturned the previous assumption that cell necrosis was not controlled by signaling pathway. Necroptosis plays a role in initiation and development of many diseases, including inflammatory diseases, cardiovascular diseases and neurological diseases. Furthermore, research proved that inducing necroptosis of tumor cells could inhibit tumor cell growth or promote tumor cell death, which is a promising strategy to treat neoplasm and overcome drug resistance problem of tumor treatment. Therefore, necroptosis can promote the development of some diseases, and it could be a potential strategy to treat tumor. Inhibiting or inducing necroptosis in different diseases with different treatment strategies is expected to treat many clinical diseases. Therefore, developing necroptotic inducers and inhibitors is of great significance in fields of both scientific research and clinical application. This article reviews the underlying mechanism of necroptosis under different pathophysiological situations and innovatively summarizes therapeutic potentials of inducers and inhibitors related to necroptotic signaling pathways in various diseases. Related Articles | Metrics

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Effect of protein phosphatase 2A on energy metabolism WU Ruo-lan, ZHANG Yue, YU Run-hua, DING Ze-yu, HUANG Ying 2020, 40 (11):  1530-1535.  doi: 10.3969/j.issn.1674-8115.2020.11.017 Abstract ( 959 )   PDF (8726KB) ( 296 )   Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase consisting of three subunits, namely A, B and C. Studies have shown that PP2A plays an important role in energy metabolism, DNA damage and repair, protein translation, cell cycle regulation and signal transduction by catalyzing the dephosphorylation of proteins and participating in the regulation of a variety of enzymes and transcription factors. This article reviews the structure and regulation of PP2A, its effect on energy metabolism and the occurrence of related diseases. Related Articles | Metrics

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Research progress of ovarian function regulated by ovarian material metabolism through Hippo signaling pathway LI Jia1, 2, YUAN Shu-sheng3, CAO Xiu-ping4, WANG Xin-nan5, HUANG Jian1, 6, ZHENG Yue-hui2, 6 2020, 40 (11):  1536-1539.  doi: 10.3969/j.issn.1674-8115.2020.11.018 Abstract ( 858 )   PDF (7175KB) ( 323 )   Hippo signaling pathway exists in drosophila and mammals, which is mainly composed of upstream modulators, core components and downstream modulators and has physiological functions such as cell proliferation, differentiation and cell cycle. In recent years, some research has shown that the Hippo signaling pathway can participate in three major substances, including glucose metabolism, mevalonate metabolism and glutamine metabolism, either alone or in combination with the AMP-activated protein kinase (AMPK) signaling pathway and the mammalian target of rapamycin (mTOR) signaling pathway. The relationship between Hippo signaling pathway and ovarian material metabolism is a research hotspot that has emerged in recent years. In this review, we summarize research progress that the Hippo signaling pathway regulates the maturation of follicles, polycystic ovary syndrome and ovarian cancer, through either alone or in combination with the AMPK signaling pathway and the mTOR signaling pathway. Related Articles | Metrics

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Research progress of age estimation based on different developmental stages of teeth SHEN Shi-hui, TAO Jiang 2020, 40 (11):  1540-1543.  doi: 10.3969/j.issn.1674-8115.2020.11.019 Abstract ( 693 )   PDF (5853KB) ( 309 )   Age estimation plays an important role in many fields, such as forensic science and sports medicine. Compared with skeletal maturity, the development of teeth is less affected by the environment, and dental age is related to the development and mineralization of different growth stages. Therefore, the dental age is crucial for individual’s age estimation. The paper reviews several methods of dental age estimation, such as those of morphology, biochemistry and radiology, as well as the application, and reviews scope and limitations of the methods. Related Articles | Metrics

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Research progress on endometriosis-related immune events GAO Han, ZHANG Ping 2020, 40 (11):  1544-1549.  doi: 10.3969/j.issn.1674-8115.2020.11.020 Abstract ( 779 )   PDF (9127KB) ( 204 )   Endometriosis is a benign gynecologic disorder prevalent in 10%–15% of women at the reproductive age worldwide. Characterized by the presence of ectopic endometrial cells and stroma in various locations outside the endometrium, it is responsible for symptoms, including chronic pelvic pain, dysmenorrhea and subfertility, which significantly degrade the quality of the life of women. The etiology and pathophysiology of endometriosis remains to be elucidated. Changes in hormone level, immunoreaction, cytokines and chemokines in patients with endometriosis have been reported, and the data suggest that these alterations contribute to the pathology and symptoms of the disease. Furthermore, the association between autoimmunity and endometriosis has received increasing attention. Related Articles | Metrics

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Analysis on factors related to disease activity of patients with Behcet disease ZHU Zhu*, GE Wen-jing*, QIAN Li-ping, LUAN Wei 2020, 40 (11):  1550-1553.  doi: 10.3969/j.issn.1674-8115.2020.11.021 Abstract ( 786 )   PDF (5382KB) ( 273 )   Objective · To analyze the related factors of disease activity of Behcet disease (BD) patients. Methods · The clinical records of 178 patients with BD who were admitted to the Department of Rheumatology and Immunology, Renji Hospital South Campus, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2018 were collected, and the clinical manifestations and laboratory indexes of the patients were analyzed. Electronic medical record-based activity index (EMRAI) was used to evaluate the disease activity, of which the related factors were explored by univariate analysis and Logistic regression analysis. Results · The ratio of males to females in 178 BD patients was 1.67:1. The results of single factor analysis showed that there were statistically significant differences in EMRAI scores among the patients with different genders, education levels and courses of disease, as well as between the patients with or without abnormal C-reactive protein, paroxysmal abdominal pain and temperature rise (P<0.05). Multivariate Logistic regression analysis showed that the related factors of EMRAI score were course of disease, C-reactive protein and treatment plan (P<0.05). Conclusion · The disease activity of BD patients is correlated with the course of disease, C-reactive protein and treatment plan. Related Articles | Metrics

Techniques and methods

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Establishment and internal validation of a prognostic model for elderly patients after lung cancer surgery based on SEER HE Chun-ming, YIN Hang, TANG Jian, DING Yi-zong, FU Yu-jie, ZHAO Xiao-jing 2020, 40 (11):  1554-1561.  doi: 10.3969/j.issn.1674-8115.2020.11.022 Abstract ( 959 )   PDF (7949KB) ( 328 )   Objective · To explore the prognostic factors for elderly patients after lung cancer surgery, and establish a prognostic nomogram to predict their prognosis with multiple factors. Methods · The surveillance, epidemiology and end results (SEER) database was used to obtain clinical data of elderly patients after lung cancer surgery, and Kaplan-Meier method was performed to calculate overall survival (OS) and lung cancer-specific survival (LCSS). Cox univariate and multivariate analysis was displayed to determine the independent predictors of postoperative lung cancer in elderly patients, and the independent predictors were selected to draw nomogram. In addition, the internal validation and effectiveness of the model were performed by Bootstrap method, concordance index (C-index) and ROC curve, the discriminative ability was compared with tumor node metastasis classification (TNM classification) system. Results · A total of 14 891 patients were included in the study. The age, gender, the primary site of tumor, tumor pathological type, TNM classification and the number of regional lymph nodes cleaning were independent predictors of elderly postoperative patients with lung cancer. The prediction model could accurately predict the prognosis of patients, and the accuracy was higher than that of TNM classification system (C-index=0.720 vs C-index=0.686). Conclusion · This study establishes a reliable prognostic model for elderly patients after lung cancer surgery based on SEER. The predictive performance is excellently demonstrated by internal validation. Related Articles | Metrics

Case report

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Large cell neuroendocrine carcinoma of prostate: a case report ZHANG Shun1, WANG Cheng2, QIAN Su-bo2, DING Yu2, WANG Chen2, DUAN Huang-qi2, XIA Wei-min2, SHEN Hai-bo2 2020, 40 (11):  1562-1570.  doi: 10.3969/j.issn.1674-8115.2020.11.023 Abstract ( 805 )   PDF (10020KB) ( 351 )   In August, 2018, a 67-year-old man presenting progressive dysuria and defecation difficulty for 7 months went to our hospital. tPSA was 24.50 ng/mL. MRI examination suggested prostate cancer, and the prostate biopsy confirmed it. Gleason score was 9 (5+4), and TNM stage after admission was cT4N0M0. Radical prostatectomy was performed after castration, combined with docetaxel chemotherapy. After operation, the patient was diagnosed as high-risk localized prostate cancer with pT4N0M0 and Gleason score 9. Local radiotherapy and castration were then given to the patient. Chest CT and PET-CT in June 2019 suggested multiple lymph node metastasis and bone metastasis. A cervical lymph node biopsy was then performed on June 10th, 2019, with CgA (+), Syn (+), PSMA (+), and PSA (+), which was consistent with prostate cancer metastasis. So the patient was diagnosed as large cell neuroendocrine carcinoma of the prostate. The patient has been treated with Abiraterone since June, 2019, which was effective in the first 2 weeks, but after 6 weeks of treatment, PSA rose again to 26.20 ng/mL. Gene detection results suggested AR amplification, so we replaced Abiraterone with docetaxel combined with cisplatin. Chest CT on November 5th, 2019 showed that the size of mediastinal and hilar lymph nodes were significantly reduced, and the pericardial effusion and pleural effusion were obviously absorbed. The patient was still alive at the end of the follow up. ECOG score was 0. Related Articles | Metrics