Depression is a complex mental disease with polygenic inheritance and a high incidence.Our understanding of the clinical manifestations and pathogenesis of depression has recently improved.Continuous progress in gene-editing technologies has increased the construction efficiency and reduced the cost of gene-knockout animals,leading to their increasing use in the fields of basic research and drug development for depression and providing a powerful tool for revealing the pathogenesis of depression.In this review,we summarize recent progress in understanding the roles and mechanisms of candidate genes in depression using knockout model mice.

PURPOSE: Vesicle-associated membrane protein 8 (VAMP8) is a soluble N-ethylmaleimide-sensitive factor receptor protein that participates in autophagy by directly regulating autophagosome membrane fusion and has been reported to be involved in tumor progression. Nevertheless, the expression and prognostic value of VAMP8 in breast cancer (BC) remain unknown. This study aimed to evaluate the clinical significance and biological function of VAMP8 in BC. METHODS: A total of 112 BC samples and 30 normal mammary gland samples were collected. The expression of VAMP8 was assessed in both BC tissues and normal mammary gland tissues via a two-step immunohistochemical detection method. RESULTS: The expression of VAMP8 in BC tissues was significantly higher than that in normal breast tissues. Furthermore, increased VAMP8 expression was significantly correlated with tumor size (p=0.007), lymph node metastasis (p=0.024) and recurrence (p=0.001). Patients with high VAMP8 expression had significantly lower cumulative recurrence-free survival and overall survival (p < 0.001 for both) than patients with low VAMP8 expression. In multivariate logistic regression and Cox regression analyses, lymph node metastasis and VAMP8 expression were independent prognostic factors for BC. CONCLUSION: VAMP8 is significantly upregulated in human BC tissues and can thus be a practical and potentially effective surrogate marker for survival in BC patients.
Autophagy ; Biomarkers ; Breast Neoplasms* ; Breast* ; Humans ; Logistic Models ; Lymph Nodes ; Mammary Glands, Human ; Membrane Fusion ; Methods ; N-Ethylmaleimide-Sensitive Proteins ; Neoplasm Metastasis ; Prognosis ; R-SNARE Proteins* ; Recurrence

Objective:To study the impact of patients with intrahepatic cholangiocellular carcinoma (ICC) who underwent surgical resection with or without lymph node dissection (LND), negative or positive lymph node metastasis detected by LND, different extents of LND, and prognostic factors on long-term prognosis of these patients.Methods:The clinical data of 162 patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2014 to October 2019 and underwent surgical resection with postoperative histopathological results confirming ICC were retrospectively analyzed. According to the degree of LND, these patients were divided into three groups: the undissected group ( n=68), N0 dissected group (prophylactic dissection) ( n=41) and N1 dissected group (positive dissection, n=53). Of 94 patients who underwent LND, 23 patients underwernt the first station LND (the routine dissection group, n=23), and 71 patients underwent extended LND (the extended dissection group, n=71). The Kaplan-Meier method was used to construct survival curves. Cox regression analysis was used to detect independent factors affecting survival and long-term prognosis of patients. Results:In this study, there were 87 males and 75 females, with a median age of 60 years.The median survival time of these 162 ICC patients was 10 months. The cumulative survival rates at 1-, 3- and 5-year after surgery were 37.6%, 16.5% and 7.9%, respectively. The 1-, 3- and 5-year cumulative survival rates of the N0 dissection group were 52.1%, 31.7% and 25.4%, respectively, which were significantly better than those of the undissected group (34.2%, 12.7%, 3.4%), and the N1 dissection group (30.3%, 11.4%, 0) ( P<0.05). There were no significant differences in postoperative survival between the extended dissection group and the routine dissection group ( P>0.05). Preoperative CA19-9 >50 U/ml ( RR=1.425, 95% CI: 0.962-2.112), maximum tumor diameter > 5 cm ( RR=0.672, 95% CI: 0.456-0.989), without LND ( RR=1.715, 95% CI: 1.140-2.580), positive margin ( RR=0.591, 95% CI: 0.390-0.897), and without postoperative adjuvant therapy ( RR=0.663, 95% CI: 0.504-0.872) were independent risk factors affecting postoperative survival ( P<0.05). Conclusions:LND in ICC patients improved long-term survival outcomes. However, extended LND did not improve prognosis of these patients. The preoperative CA19-9 level, maximum tumor diameter, lymph node dissection, surgical margin status, and postoperative adjuvant therapy were independent risk factors affecting long-term prognosis of these patients.

Objective:To establish occupational exposure limits for glyphosate in workplace air.Methods:In November 2014, by searching the documents of the United States Environmental Protection Agency (EPA) on glyphosate toxicity, the toxicity data and clinical symptoms of glyphosate toxicity were collected through various literature databases, and the target organs of glyphosate toxicity were determined. A total of 5 representative production enterprises in Jiangsu Province and Shandong Province were selected for field investigation. A total of 968 people were selected as the study subjects, including 526 workers exposed to glyphosate as the contact group, and 442 off-site (such as financial, administrative, etc.) workers with enterprises as the control group. Health examination was carried out in the exposure group and the control group to observe the damage of target organs of workers with different exposure concentrations and determine the occupational exposure limit.Results:The main target organs of glyphosate are liver and kidney and its effect on cholinesterase activity. The time-weighted average concentration (TWA) of glyphosate exposure in the exposure group was <0.03~48.91 mg/m 3, and there were statistically significant differences in liver and renal function between the exposure group and the control group ( P<0.05). When the concentration of glyphosate in the air was higher than 5 mg/m3, there was a statistically significant difference in the abnormal rate of renal function between the exposure group and the control group ( P<0.05) . Conclusion:The study sets the occupational exposure limit of glyphosate as 5 mg/m 3. The safety of this standard conforms to the relevant requirements of toxicology and occupational disease epidemiology, and also conforms to the existing economic and technological level in my country, and is highly feasible.

Objective:To establish occupational exposure limits for glyphosate in workplace air.Methods:In November 2014, by searching the documents of the United States Environmental Protection Agency (EPA) on glyphosate toxicity, the toxicity data and clinical symptoms of glyphosate toxicity were collected through various literature databases, and the target organs of glyphosate toxicity were determined. A total of 5 representative production enterprises in Jiangsu Province and Shandong Province were selected for field investigation. A total of 968 people were selected as the study subjects, including 526 workers exposed to glyphosate as the contact group, and 442 off-site (such as financial, administrative, etc.) workers with enterprises as the control group. Health examination was carried out in the exposure group and the control group to observe the damage of target organs of workers with different exposure concentrations and determine the occupational exposure limit.Results:The main target organs of glyphosate are liver and kidney and its effect on cholinesterase activity. The time-weighted average concentration (TWA) of glyphosate exposure in the exposure group was <0.03~48.91 mg/m 3, and there were statistically significant differences in liver and renal function between the exposure group and the control group ( P<0.05). When the concentration of glyphosate in the air was higher than 5 mg/m3, there was a statistically significant difference in the abnormal rate of renal function between the exposure group and the control group ( P<0.05) . Conclusion:The study sets the occupational exposure limit of glyphosate as 5 mg/m 3. The safety of this standard conforms to the relevant requirements of toxicology and occupational disease epidemiology, and also conforms to the existing economic and technological level in my country, and is highly feasible.

Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Objective:To analyze the vaginal microecological status of vaginitis population and non-vaginitis population of gynecological female outpatients.Methods:A total of 30 265 women who visited the gynecological outpatient clinic of Beijing Obstetrics and Gynecology Hospital from December 2018 to December 2020 completed vaginal microecological examination. After removing the follow-up patients, 23 181 women were divided into group with symptoms and signs of vaginitis (6 697 cases) and group without symptoms and signs of vaginitis (16 484 cases), according to whether the women with symptoms and signs of vaginitis or not. And the vaginal microecological status of the two groups was compared and analyzed.Results:(1) The total detection rate of vaginitis in the initial women was 34.87% (8 083/23 181), of which 46.10% (3 087/6 697) in group with symptoms and signs of vaginitis and 30.31% (4 996/16 484) in group without symptoms and signs of vaginitis, nearly 1/3 of the gynecological outpatients without signs and symptoms of vaginitis had vaginitis. (2) Among the types of simple vaginitis, vulvovaginal candidiasis (VVC) was the most frequent in group with symptoms and signs of vaginitis (16.01%, 1 072/6 697), followed by aerobic vaginitis (AV; 12.83%, 859/6 697), with significant differences compared with group without symptoms and signs of vaginitis (all P<0.001). There were no statistical differences between the two groups of bacterial vaginosis (BV) and trichomonal vaginitis (TV), indicating that BV and TV were more likely to be neglected (all P>0.05). (3) The proportion of various combinations of vaginitis among 2 632 cases of mixed vaginitis were, in descending order: BV+AV, VVC+AV, BV+AV+VVC, AV+TV, AV+TV+BV, BV+VVC. (4) Microecological analysis of 15 098 cases diagnosed with non-vaginitis had normal flora (including those with normal flora and those with normal flora but decreased function) in 14 013 cases (92.81%, 14 013/15 098), abnormal flora in 429 cases (2.84%, 429/15 098) and the BV intermediate in 656 cases (4.34%, 656/15 098); this indicated that the vast majority of the microecological tests were normal in the vaginal microbiota of those without vaginitis. Conclusions:Microecological examination could diagnose multiple pathogenic infections at once, and is especially important as a guide for the definitive diagnosis of mixed vaginitis and vaginitis with atypical clinical symptoms. Vaginal infections such as BV and TV that are easily overlooked should be concerned.

OBJECTIVE: To explore the direct relationship between personality (PN) and sub-health status (SHS) and their indirect association mediated by frustration quotient (FQ) and stress event (SE). METHODS: A multiple-stage stratified sampling method was used to choose the participants, and a total of 4517 eligible urban residents were selected.ANCOVA was used to analyze the independent association between personality and SHS after adjusting the demographic characteristics and lifestyle.A structural equation model was used to analyze the associations among personality, FQ, SE and SHS.Bootstrap method was used to test the direct and indirect association between personality and SHS. RESULTS: Personality was independently associated with total sub-health (=75.913, < 0.001), physical sub-health (=23.618, < 0.001), mental sub-health (=101.993, < 0.001) and social sub-health (=48.757, < 0.001).The urban residents with the personalities characterized by anger suppression, anxiety and irritability, and impatience and competitiveness had significantly lower health scores than those with a mature and steady personality ( < 0.05).Personality was associated with FQ and SE, and the indirect association between personality and physical sub-health was mainly mediated by FQ and SE (β=-0.110).Personality showed more a direct association (β=-0.172) with mental sub-health and a slightly less indirect association (β=-0.126) with mental sub-health.Personality showed a more indirect association (β=-0.113) with social SHS and slightly less direct association (β=-0.082) with social sub-health. CONCLUSIONS A mature and steady personality may help to promote the general health level, while the personalities of anger suppression, anxiety and irritability, impatience and competitiveness can be associated with the occurrence of sub-health.Building a mature and steady personality has positive effects on the health in general of an individual.
Adolescent ; Asian Continental Ancestry Group ; Health Status ; Humans ; Life Style ; Personality

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.