Objective: To understand the impact of childhood trauma on psychological distress among upper grade elemetary school students, and to explore the mediating role of leisure activities in the relationship, so as to provide a basis for developing mental health intervention strategies. Methods: From August to November 2024, a combination of convenience sampling and stratified cluster random sampling was employed to recruit 1 373 fourth to sixth grade students from four primary schools in Harbin. The Childhood Trauma Questionnaire(CTQ), a self designed leisure activity scale (including active and passive leisure activities), and the Kessler Psychological Distress Scale (K10) were used to assess childhood trauma experiences, leisure activities, and levels of psychological distress. Spearman correlation analysis and linear regression analysis were conducted to explore the relationships among childhood trauma, leisure types, leisure time, and psychological distress. Based on the mediation analysis framework proposed by Hayes (Model 4), the mediating role of leisure types in the relationship between childhood trauma and psychological distress was examined. Results: Totally 19.1% of the upper elemetary school students exhibited psychological distress, while 30.2% had experienced childhood trauma. During school days, 64.6% of the students were reported of having leisure time concentrated between 1 and 5 hours per day, whereas 67.4% reported leisure time exceeding 5 hours per day on weekends. After controlling for potential demographic confounders such as gender, grade, ethnicity, household registration, being an only child, parents educational level, co residence, and whether parents are first time married,linear regression analysis showed that childhood trauma experience had positive predictive effect on psychological distress in upper primary school students( β =0.20, P <0.01). Leisure time showed no statistically significant association with psychological distress, both on school days ( β =-0.58 to -0.56) and weekends ( β =0.26- 0.98 )(all P >0.05). Active leisure activities were negatively associated with psychological distress ( β =-0.20), while passive leisure activities were positively associated with psychological distress ( β =0.29)(both P <0.01). Leisure type partially mediated the relationship between childhood trauma and psychological distress, accounting for 11.7% of the indirect effect. Conclusion Childhood trauma experiences positively predict psychological distress in upper elementary school students, and affect psychological distress through active leisure and passive leisure.

Objective To analyze the literature on the"gut-liver axis"theory,and to understand the hotspots and development trends of the"gut-liver axis"theory.Methods Literatures related to the"gut-liver axis"in databases were searched from the establishment of the database to October 1,2024.A total of 292 Chinese and 1591 English articles were included.CiteSpace 6.4R1 and VOSviewer1.6.20 software were used for analysis.Results High-frequency Chinese keywords included"gut-liver axis""intestinal flora""non-alcoholic fatty liver disease"etc,10 clusters were formed.High-frequency English keywords included"gut-liver axis""gut microbiota""inflammation",etc,14 clusters were formed.Conclusion The research on the"gut-liver axis"is increasing year by year,and the direction of liver fibrosis and immunity will be the hot direction in the future.

Objective To analyze the literature on the"gut-liver axis"theory,and to understand the hotspots and development trends of the"gut-liver axis"theory.Methods Literatures related to the"gut-liver axis"in databases were searched from the establishment of the database to October 1,2024.A total of 292 Chinese and 1591 English articles were included.CiteSpace 6.4R1 and VOSviewer1.6.20 software were used for analysis.Results High-frequency Chinese keywords included"gut-liver axis""intestinal flora""non-alcoholic fatty liver disease"etc,10 clusters were formed.High-frequency English keywords included"gut-liver axis""gut microbiota""inflammation",etc,14 clusters were formed.Conclusion The research on the"gut-liver axis"is increasing year by year,and the direction of liver fibrosis and immunity will be the hot direction in the future.

Objective:To explore the value of transvaginal ultrasound (TVS) combined with neutrophil to lymphocyte ratio (NLR) in postmenopausal women with endometrial cancer(EC).Methods:A retrospective analysis was conducted on 348 postmenopausal patients who underwent hysteroscopy or surgery in the Obstetrics and Gynecology Hospital of Fudan University from January 2019 to December 2021 and had pathological results of EC, and they were included in the malignant group. One hundred and six benign patients with pathological results in the same period were randomly selected for inclusion in the benign group. The differences in age, menopausal time, gravidity, body mass index (BMI), post-menopausal bleeding, TVS and NLR were compared between the two groups. Binary Logistic regression analysis was performed to determine the independent predictive factors for endometrial cancer in postmenopausal women. ROC curves were plotted to evaluate the diagnostic efficacy of predicting EC in postmenopausal women.Results:Parity (≥2 times), post-menopausal bleeding, intrauterine fluid, the diameter of the mass, blood flow and NLR showed statistically significant differences between the malignant group and the benign group (all P<0.05). Logistic regression analysis showed that post-menopausal bleeding, intrauterine fluid and long diameter of the mass were independent predictors for EC in postmenopausal women( OR=0.433, P=0.006; OR=14.933, P<0.001; OR=1.062, P=0.001). The area under the curve (AUC) of EC in postmenopausal women was 0.901(95% CI=0.867-0.934) by the combination of the above independent factors and the parameters of P<0.10 (blood flow and NLR), the sensitivity was 78.4% and the specificity was 90.6%. Conclusions:The combination of post-menopausal bleeding, intrauterine fluid, the diameter of the mass, blood flow and NLR have certain clinical application value in predicting EC in postmenopausal women.

Objective:To explore the value of transvaginal ultrasound (TVS) combined with neutrophil to lymphocyte ratio (NLR) in postmenopausal women with endometrial cancer(EC).Methods:A retrospective analysis was conducted on 348 postmenopausal patients who underwent hysteroscopy or surgery in the Obstetrics and Gynecology Hospital of Fudan University from January 2019 to December 2021 and had pathological results of EC, and they were included in the malignant group. One hundred and six benign patients with pathological results in the same period were randomly selected for inclusion in the benign group. The differences in age, menopausal time, gravidity, body mass index (BMI), post-menopausal bleeding, TVS and NLR were compared between the two groups. Binary Logistic regression analysis was performed to determine the independent predictive factors for endometrial cancer in postmenopausal women. ROC curves were plotted to evaluate the diagnostic efficacy of predicting EC in postmenopausal women.Results:Parity (≥2 times), post-menopausal bleeding, intrauterine fluid, the diameter of the mass, blood flow and NLR showed statistically significant differences between the malignant group and the benign group (all P<0.05). Logistic regression analysis showed that post-menopausal bleeding, intrauterine fluid and long diameter of the mass were independent predictors for EC in postmenopausal women( OR=0.433, P=0.006; OR=14.933, P<0.001; OR=1.062, P=0.001). The area under the curve (AUC) of EC in postmenopausal women was 0.901(95% CI=0.867-0.934) by the combination of the above independent factors and the parameters of P<0.10 (blood flow and NLR), the sensitivity was 78.4% and the specificity was 90.6%. Conclusions:The combination of post-menopausal bleeding, intrauterine fluid, the diameter of the mass, blood flow and NLR have certain clinical application value in predicting EC in postmenopausal women.

Objective:To investigate the therapeutic effect and safety of pomadomide combined with cyclophosphamide and dexamethasone (PCD) in the treatment of relapsed/refractory multiple myeloma (MM).Methods:The clinical data of 20 relapsed/refractory MM patients receiving PCD regimen in the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College from March 2021 to June 2022 were retrospectively analyzed; and 29 relapsed/refractory MM patients receiving other regimens including DECP (dexamethasone+etoposide+cyclophosphamide+cisplatin, 13 cases) and VCD (bortezomib+ cyclophosphamide+ dexamethasone, 16 cases) during the same period were treated as the control group. The efficacy and adverse effects of both groups were compared after 4 cycles of treatment.Results:After 4 cycles of treatment, the overall response rate (ORR) and the clinical benefit rate (CBR) of 20 cases in PCD group was 70.0% (14/20) and 85.0% (17/20), respectively; among 20 cases, there were 5 cases of complete response (CR), 4 cases of very good partial remission (VGPR), 5 cases of partial remission (PR), 3 cases of minimal remission (MR), 2 cases of stable disease (SD), 1 case of the progression of the disease (PD). ORR and CBR of 29 cases in the control group was 41.4% (12/29) and 65.5% (19/29), respectively; among 29 cases, there were 2 cases of CR, 3 cases of VGPR, 7 cases of PR, 7 cases of MR, 5 cases of SD, 5 cases of PD. There was a statistically significant difference in ORR of both group ( χ2 = 3.89, P = 0.048), while the difference in CBR of both group was not statistically significant ( χ2 = 2.30, P = 0.129). There were 2 patients with renal impairment achieving CR in PCD group and 1 patient with renal impairment achieving CR in the control group ( P = 0.152); 1 genetically high-risk patient achieved CR in PCD group and none of patients in the control group achieved CR, and the difference was statistically significant ( P>0.05). The common hematological adverse effects of two groups were anemia, neutropenia, thrombocytopenia; the common non-hematological adverse effects were malaise, infection and fatigue, and the differences were statistically significant (all P>0.05). The incidence of grade 3-4 infection was 25.0% (5/20) in PCD group and the disease was under the control after anti-infective therapy, and the incidence of grade 3-4 infection was 24.1% (7/29) in the control group; and the difference was not statistically significant ( P > 0.05). Conclusions:PCD regimen has good clinical efficacy and safety in treatment of relapsed/refractory MM.

With the rapid development of gene editing technology, the study of spermatogonial stem cells (SSCs) holds great significance in understanding spermatogenesis and its regulatory mechanism, developing transgenic animals, gene therapy, infertility treatment and protecting rare species. Biogenesis of lysosome-related organelles complex 1 subunit 1 (BLOC1S1) is believed to have anti-brucella potential. Exploring the impack of BLOC1S1 on goat SSCs not only helps investigate the ability of BLOC1S1 to promote SSCs proliferation, but also provides a cytological basis for disease-resistant breeding research. In this study, a BLOC1S1 overexpression vector was constructed by homologous recombination. The BLOC1S1 overexpression cell line of goat spermatogonial stem cells was successfully constructed by lentivirus packaging, transfection and puromycin screening. The overexpression efficiency of BLOC1S1 was found to be 18 times higher using real time quantitative PCR (RT-qPCR). Furthermore, the results from cell growth curve analysis, flow cytometry for cell cycle detection, and 5-ethynyl-2'-deoxyuridine (EdU) staining showed that BLOC1S1 significantly increased the proliferation activity of goat SSCs. The results of RT-qPCR, immunofluorescence staining and Western blotting analyses revealed up-regulation of proliferation-related genes (PCNA, CDK2, CCND1), and EIF2S3Y, a key gene regulating the proliferation of spermatogonial stem cells. These findings strongly suggest that the proliferative ability of goat SSCs can be enhanced through the EIF2S3Y/ERK pathway. In summary, this study successfully created a goat spermatogonial stem cell BLOC1S1 overexpression cell line, which exhibited improved proliferation ability. This research laid the groundwork for exploring the regulatory role of BLOC1S1 in goat spermatogonia and provided a cell platform for further study into the biological function of BLOC1S1. These findings also establish a foundation for breeding BLOC1S1 overexpressing goats.
Animals ; Male ; Goats ; Stem Cells ; Spermatogonia/metabolism* ; Cell Proliferation ; Flow Cytometry ; Testis/metabolism*

Objective:To investigate the current sedation level of patients with mechanical ventilation in ICU, and to explore the influence of early different sedation levels on clinical outcomes, so as to provide theoretical basis for better guidance of clinical sedation evaluation and implementation of sedation strategy management.Methods:This study was a retrospective longitudinal study. The 201 patients with invasive mechanical ventilation who underwent sedation in the Department of Intensive Care Medicine of the First Affiliated Hospital of Guangxi Medical University from January to December 2021 were selected by convenience sampling method. According to the results of Richmond Agitation-Sedation Scale(RASS), the patients were divided into deep sedation group (98 cases) and shallow sedation group (103 cases). The influencing factors of endotracheal intubation retention time and outcome were investigated by Cox multifactor analysis.Results:In the early sedation ≤48 h after the start of mechanical ventilation, 63.2%(2 143/3 389) of patients with invasive mechanical ventilation had a RASS score of shallow sedation, 35.2%(1 194/3 389) of patients with deep sedation, and 1.5%(52/3 389) of patients with insufficient sedation. Cox multivariate regression analysis showed that age, sedation level, duration of invasive mechanical ventilation and continuous renal replacement therapy were the factors influencing the indentation time of tracheal insertion ( χ2 values were 4.73 to 74.31, all P<0.05); early deep sedation was a risk factor for delayed extubation ( HR=0.499, 95% CI 0.276-0.903, P<0.05); gender, sedation level, invasive mechanical ventilation duration, acute physiology and chronic health evaluation Ⅱ scores, admission mode, continuous renal replacement therapywere the influencing factors of patient outcomes ( χ2 values were 4.41 to 26.20, all P<0.05). The deeper the sedation, the worse the patient outcomes ( HR=0.568, 95% CI 0.335-0.963 all P<0.05) . Conclusions:The early sedation level is related to the retention time and outcome of tracheal intubation in ICU patients with mechanical ventilation, and different sedation levels affect the clinical outcome of patients. The retention time of tracheal intubation in patients with shallow sedation was shortened, which was beneficial to the outcome of patients.Therefore, sedation evaluation should be strengthened in clinical work, and sedation methods should be selected according to the needs of patients. In the absence of contraindications, the shallow sedation strategy should be implemented as soon as possible. This study provides some reference and theoretical basis for the formulation and management of clinical sedation strategies.

As main recipient cells for porcine reproductive and respiratory syndrome virus (PRRSV), porcine alveolar macrophage (PAM) are involved in the progress of several highly pathogenic virus infections. However, due to the fact that the PAM cells can only be obtained from primary tissues, research on PAM-based virus-host interactions remains challenging. The improvement of induced pluripotent stem cells (iPSCs) technology provides a new strategy to develop IPSCs-derived PAM cells. Since the CD163 is a macrophage-specific marker and a validated receptor essential for PRRSV infection, generation of stable porcine induced pluripotent stem cells lines containing CD163 reporter system play important roles in the investigation of IPSCs-PAM transition and PAM-based virus-host interaction. Based on the CRISPR/Cas9- mediated gene editing system, we designed a sgRNA targeting CD163 locus and constructed the corresponding donor vectors. To test whether this reporter system has the expected function, the reporter system was introduced into primary PAM cells to detect the expression of RFP. To validate the low effect on stem cell pluripotency, we generated porcine iPSC lines containing CD163 reporter and assessed the pluripotency through multiple assays such as alkaline phosphatase staining, immunofluorescent staining, and EdU staining. The red-fluorescent protein (RFP) expression was detected in CD163-edited PAM cells, suggesting that our reporter system indeed has the ability to reflect the expression of gene CD163. Compared with wild-type (WT) iPSCs, the CD163 reporter-iPSCs display similar pluripotency-associated transcription factors expression. Besides, cells with the reporter system showed consistent cell morphology and proliferation ability as compared to WT iPSCs, indicating that the edited-cells have no effect on stem cell pluripotency. In conclusion, we generated porcine iPSCs that contain a CD163 reporter system. Our results demonstrated that this reporter system was functional and safe. This study provides a platform to investigate the iPS-PAM development and virus-host interaction in PAM cells.
Swine ; Animals ; Induced Pluripotent Stem Cells/metabolism* ; Receptors, Cell Surface/genetics* ; Antigens, CD/metabolism* ; Porcine respiratory and reproductive syndrome virus/genetics*

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a K _d value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.