Objective: To analyze the correlation and gender differences between adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) and depression and anxiety symptoms among middle school students, so as to provide a reference for promoting the mental health of middle school students. Methods: With a stratified random cluster sampling method, a total of 6 656 middle school students in 4 cities, including Nanchang, Shenyang, Taiyuan, and Zhengzhou, were selected as research subjects from October 2021 to October 2022. The Adverse Childhood Experiences International Questionnaire (ACEs-IQ), Benevolent Childhood Experiences Scale (BCEs), Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorders-7 (GAD-7) scale were used to conduct questionnaire surveys.The Chi square test was used to compare the reporting rates of depression and anxiety symptoms among middle school students in different groups, and a Logistic regression model was established to analyze the effects of ACEs and PCEs on depression and anxiety symptoms among middle school students and their gender differences. Results: The reporting rate of depressive symptoms among middle school students was 20.1%, and the reporting rate of anxiety symptoms was 13.9% . ACEs were positively correlated with depression and anxiety symptoms among middle school students (depression symptoms: OR =1.20, 95% CI =1.18-1.22, anxiety symptoms: OR =1.18, 95% CI =1.16-1.20), while PCEs were negatively correlated with depression and anxiety symptoms among middle school students(depression symptoms: OR =0.84, 95% CI = 0.83 -0.86, anxiety symptoms: OR =0.85, 95% CI =0.83-0.87) ( P <0.05). In the general population (depression symptoms ： OR =0.99, 95% CI = 0.98- 0.99, anxiety symptoms: OR =0.99, 95% CI =0.99-1.00) and among girls (depression symptoms: OR = 0.98 , 95% CI = 0.97- 0.99 , anxiety symptoms ： OR =0.99, 95% CI =0.98-1.00), the interaction term between ACEs and PCEs were negatively correlated with depression and anxiety symptoms ( P <0.05). Conclusions ACEs significantly affect the depression and anxiety symptoms of middle school students, while PCEs can help reduce the impact of ACEs on the depression and anxiety symptoms of middle school students, girls are more susceptible to the impact of early experiences than boys. It should focus on gender differences, formulate comprehensive mental health protection strategies, to promote the mental health development of middle school students.

ObjectiveTo investigate the effects of berbamine hydrochloride on sorafenib resistance in hepatocellular carcinoma cells and the underlying mechanisms. MethodThe sorafenib-resistant cell line SMMC-7721/S was selected by the concentration increment method starting at 1.25 μmol·L^-1 sorafenib. Both SMMC-7721 and SMMC-7721/S cells were treated with 0， 2.5， 5， 10， 15， 20 μmol·L^-1 sorafenib， and the cell counting kit-8 （CCK-8） assay was employed to determine the half maximal inhibitory concentration （IC₅₀） and calculate the resistance index （RI）. Western blot was conducted to compare the expression of proteins involved in autophagy and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway between SMMC-7721 and SMMC-7721/S cells. Furthermore， SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 2.5， 5， 10 μmol·L^-1 sorafenib， and the cell growth was assessed by the CCK-8 assay. In addition， SMMC-7721 and SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 5 μmol·L^-1 sorafenib， and the cell proliferation was examined by the colony formation assay. The immunofluorescence assays with Microtubule-associated protein 1 light chain 3 （LC3） and LysoTracker as probes were employed to assess the lysosomal acidification in SMMC-7721 cells treated with 5 μmol·L^-1 berbamine hydrochloride or 0.1 μmol·L^-1 autophagy inhibitor bafilomycin A1 （Baf）. Further， the expression of proteins involved in autophagy and PI3K/Akt/mTOR signaling pathway was determined by Western blot and compared between groups. ResultSorafenib showed the IC₅₀ of 9.56 mol·L^-1 （P<0.01） and 7.99 mol·L^-1 for SMMC-7721/S and SMMC-7721 cells， respectively， at 24 h. The resistance index （RI） of SMMC-7721/S for sorafenib was 1.20 （P<0.01）， which indicated mild resistance. Compared with SMMC-7721 cells， SMMC-7721/S cells exhibited up-regulated expression of p-mTOR， p-Akt， and LC3Ⅱ， down-regulated expression of p62 protein （P<0.01）， and unchanged Akt protein level. CCK-8 and colony formation assays demonstrated that the combination of berbamine hydrochloride and sorafenib exhibited a synergistic effect （Q>1.15）， with berbamine hydrochloride partially reversing the resistance of liver cancer cells to sorafenib. The immunofluorescence detection of LC3 revealed that berbamine hydrochloride and Baf significantly increased LC3 in SMMC-7721 cells. The detection with LysoTracker as the probe showed that berbamine hydrochloride inhibited the acidity of lysosomes in SMMC-7721 cells （P<0.01）， indicating the suppression of autophagy. Berbamine hydrochloride further enhanced the downregulation of p-mTOR and p-Akt protein levels and did not change the Akt protein level in SMMC-7721 cells exposed to sorafenib. Berbamine hydrochloride inhibited the increase in p-mTOR expression， down-regulated the p-Akt protein level， and did not change the total Akt protein level in the SMMC-7721/S cells exposed to sorafenib. ConclusionBerbamine hydrochloride can ameliorate the resistance of liver cancer cells to sorafenib by inhibiting cellular autophagy and the PI3K/Akt/mTOR signaling pathway.

Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.

Objective:To explore the influence of pulmonary nodule size, nodule location, fissure, surgical approach, surgical entrance, postoperative pathology, surgical method and other factors on the relevant information of basal segmentectomy under thoracoscopy.Methods:Retrospectively analyze 103 patients who underwent thoracoscopic basal segmentectomy of the lung from January 2023 to February 2024. According to the classification of nodule size, nodule position, development of pulmonary fissure, surgical approach, number of surgical entrance, postoperative pathology, surgical method, tc., the influence of single factor Logistic regression analysis was used to explore the influence of various factors on the relevant information of pulmonary basal segmentectomy under thoracoscopy. Results:When the dependent variable was the surgery duration, single factor analysis showed that CT location( P=0.024), nodule composition( P=0.029), surgical entry( P=0.002), surgical method( P<0.001), and surgical approach( P=0.052) significantly influenced the surgery duration. Variables with P<0.1 in the single factor analysis were included in the multivariate analysis, which showed that surgical entry and surgical method significantly influenced surgery duration( P<0.05). When the dependent variable was the total hospitalization cost, single factor analysis showed that CT location, surgical approach, and surgical method significantly influenced the total hospitalization cost( P<0.1). Multiple factor analysis showed that the surgical method affected the total hospitalization cost, with significantly higher costs when S9 or S10 lung segments were resected( P=0.050). When the dependent variable was postoperative drainage duration, single factor analysis showed that the condition of the lung fissures significantly influenced postoperative drainage duration( P=0.028). Multiple factor regression analysis showed that incomplete lung fissure development significantly increased the possibility of postoperative air leaks( P=0.034). Conclusion:The surgical access may significantly affect the operation time, which is the use of uniport thoracoscopy is shorter than the multi-port operation time, the surgical method does not contain S9/S10 is shorter than that of S9/S10, and the total cost of hospitalization is lower. The completeness of the fissure will significantly decrease the possibility of postoperative pulmonary leakage.

Objective:To explore whether lung microorganisms influence the occurrence and development of early lung adenocarcinoma by analyzing the presence and changes of local microorganisms in early lung adenocarcinoma.Methods:Tumor tissues and alveolar lavage fluid were collected from 32 patients diagnosed with lung adenocarcinoma at the China-Japan Friendship Hospital. Nextseq550DX was used for DNA sequencing. R language was used to calculate the number of microorganisms in the tumor tissue and alveolar lavage fluid samples of different stages and grades. species and diversity, and use statistical methods such as TSEA and LEfSe analysis to compare the diversity and differences of microorganisms in different groups. Results:Both Actinobacteria and Proteobacteria accounted for a higher proportion in both the tumor tissue and alveolar lavage fluid samples of patients with lung adenocarcinoma. The number of microorganisms detected in the tumor tissue was greater than that in the lavage fluid, and the alpha diversity was higher, but the difference Not significant( P<0. 05). According to the analysis of differences in lung microorganisms in patients with different pathological grades: In the two samples, invasive adenocarcinoma has more microorganisms than carcinoma in situ + microinvasive carcinoma, and the alpha diversity of the lavage fluid is significantly higher, and the comparison between the groups is statistically significant( P=0. 011); the difference in β diversity was not statistically significant( P>0. 05). Group analysis based on different pathological types: the invasive adenocarcinoma group samples showed a decrease in Proteobacteria, the carcinoma in situ + minimally invasive cancer group was mainly composed of Proteobacteria, and most of the microorganisms related to lung cancer differences analyzed in each group belonged to Proteobacteria and Actinobacteria. Phylum. Conclusion:Most of the microbes in tumor tissues and lavage fluid of lung adenocarcinoma belong to the Actinobacteria and Proteobacteria. Most of the differentially associated microbes of lung cancer under different classifications also belong to Proteobacteria and Actinobacteria, which are the main characteristics of lung microbial composition in patients with early-stage lung adenocarcinoma.

Objective:To explore the relationship between bullying and depressive symptoms in college students,the mediating role of mobile phone addiction and the moderating role of gender.Methods:Totally 1 499 college students in Nantong City were selected to evaluate bullying experience,mobile phone addiction tendency and depressive symptoms with the Revised Adolescent Peer Relations Instrument-Bully and Target(RAPRI-T),Smart-phone Addiction Scale-Short Version(SAS-SV),Patient Health Questionnaire Depression 9-item(PHQ-9).SPSS macro program PROCESS 3.2 was used to examine the mediating role of mobile phone addiction and the modera-ting role of gender.Results:Different forms of bullying,traditional verbal bullying had the highest detection rate.There were positive correlations among bullying and the scores of SAS-SV and PHQ-9(r=0.17-0.42,Ps＜0.001).In the relationship between bullying scores and PHQ-9 scores,SAS-SV scores played a partial mediating role,and the mediating effect accounts for 26.70％of the total effect.The interaction terms between bullying and genders had statistical significance with PHQ-9 scores(β=0.09,P＜0.001),as the bullying scores increased,the PHQ-9 scores were higher in girls than in boys.Conclusion:Mobile phone addiction plays a partial mediating role in the association between bullying and depressive symptomsin college students,and the association between bull-ying and depressive symptoms is moderated by gender factors.

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Objective:To evaluate the 1-year postoperative efficacy of four bariatric procedures, namely sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S), and biliopancreatic diversion with duodenal switch (BPD/DS) for treating super obesity.Methods:In this retrospective observational study, we analyzed the clinical data of 40 patients with super obesity (body mass index [BMI]≥50 kg/m 2) who had undergone bariatric surgery in the China-Japan Union Hospital of Jilin University from November 2015 to December 2020. The study cohort consisted of 21 men and 19 women of average age 31.7±9.0 years. The preoperative weight and BMI were (159.2±16.9) kg and (53.4±3.0) kg/m 2, respectively. Prior to the surgery, 30 individuals had hypertension, 27 hyperuricemia, 15 type 2 diabetes, 10 abnormally high total cholesterol, 20 abnormally high triglycerides, and 24 abnormally high low-density lipoprotein. We divided the participants into four groups according to the type of operation: SG group ( n=16), RYGB group ( n=9), SADI-S group ( n=9) and BPD/DS group ( n=6). We examined the following factors: weight, BMI, excess weight loss (%), total weight loss (%), and remission of preoperative metabolic diseases (including hypertension, hyperuricemia, type 2 diabetes, and hyperlipidemia) 3, 6, and 12 months after surgery. The variables assessed for hypertension were systolic and diastolic blood pressure; for type 2 diabetes, glycated hemoglobin; and for hyperlipidemia, total cholesterol, triglycerides, and low-density lipoprotein 1-year after the surgery. The safety of surgery was also assessed. Results:All patients successfully completed laparoscopic procedures, none of them requiring conversion to laparotomy. The amount of blood loss during surgery was less than 50 mL. Postoperative hospital stay was 6–16 days. There were no deaths during the perioperative period. However, two postoperative complications occurred in the RYGB group, namely bleeding and anastomotic leakage. No complications were detected in the other groups. At 3, 6, and 12 months after surgery, percentage of excess weight loss was 36.6±11.0, 62.4±15.7, and 68.2±16.0 ( F=21.830, P<0.001) in the SG group; 30.6±6.9, 42.5±5.8, and 50.6±11.1 ( F=13.222, P<0.001) in the RYGB group; 39.7±7.8, 54.6±12.7, and 81.9±12.0 ( F=33.821, P<0.001) in the SADI-S group; and 40.2±4.8, 57.7±11.8, and 82.8±14.9 ( F=21.552, P<0.001), respectively, in the BPD/DS group. The percentage of excess weight loss increased significantly over the 12-month observation period in all groups . Compared with before surgery, hypertension and hyperuricemia in the SG, SADI-S, and BPD-DS groups showed significant improvement after one year (all P<0.05). However, only the SADI-S group exhibited a significant decrease in glycosylated hemoglobin concentrations ( P=0.038). Only the BPD-DS group showed significant decreases in various indicators of hyperlipidemia (all P<0.05). The improvements in obesity-related complication indexes did not reach statistical significance in the RYGB group (all P>0.05). Conclusion:SG, RYGB, SADI-S and BPD/DS are all safe and effective treatments for super obesity. All of these procedures can improve the associated metabolic diseases to a certain extent.

Objective:To evaluate the 1-year postoperative efficacy of four bariatric procedures, namely sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S), and biliopancreatic diversion with duodenal switch (BPD/DS) for treating super obesity.Methods:In this retrospective observational study, we analyzed the clinical data of 40 patients with super obesity (body mass index [BMI]≥50 kg/m 2) who had undergone bariatric surgery in the China-Japan Union Hospital of Jilin University from November 2015 to December 2020. The study cohort consisted of 21 men and 19 women of average age 31.7±9.0 years. The preoperative weight and BMI were (159.2±16.9) kg and (53.4±3.0) kg/m 2, respectively. Prior to the surgery, 30 individuals had hypertension, 27 hyperuricemia, 15 type 2 diabetes, 10 abnormally high total cholesterol, 20 abnormally high triglycerides, and 24 abnormally high low-density lipoprotein. We divided the participants into four groups according to the type of operation: SG group ( n=16), RYGB group ( n=9), SADI-S group ( n=9) and BPD/DS group ( n=6). We examined the following factors: weight, BMI, excess weight loss (%), total weight loss (%), and remission of preoperative metabolic diseases (including hypertension, hyperuricemia, type 2 diabetes, and hyperlipidemia) 3, 6, and 12 months after surgery. The variables assessed for hypertension were systolic and diastolic blood pressure; for type 2 diabetes, glycated hemoglobin; and for hyperlipidemia, total cholesterol, triglycerides, and low-density lipoprotein 1-year after the surgery. The safety of surgery was also assessed. Results:All patients successfully completed laparoscopic procedures, none of them requiring conversion to laparotomy. The amount of blood loss during surgery was less than 50 mL. Postoperative hospital stay was 6–16 days. There were no deaths during the perioperative period. However, two postoperative complications occurred in the RYGB group, namely bleeding and anastomotic leakage. No complications were detected in the other groups. At 3, 6, and 12 months after surgery, percentage of excess weight loss was 36.6±11.0, 62.4±15.7, and 68.2±16.0 ( F=21.830, P<0.001) in the SG group; 30.6±6.9, 42.5±5.8, and 50.6±11.1 ( F=13.222, P<0.001) in the RYGB group; 39.7±7.8, 54.6±12.7, and 81.9±12.0 ( F=33.821, P<0.001) in the SADI-S group; and 40.2±4.8, 57.7±11.8, and 82.8±14.9 ( F=21.552, P<0.001), respectively, in the BPD/DS group. The percentage of excess weight loss increased significantly over the 12-month observation period in all groups . Compared with before surgery, hypertension and hyperuricemia in the SG, SADI-S, and BPD-DS groups showed significant improvement after one year (all P<0.05). However, only the SADI-S group exhibited a significant decrease in glycosylated hemoglobin concentrations ( P=0.038). Only the BPD-DS group showed significant decreases in various indicators of hyperlipidemia (all P<0.05). The improvements in obesity-related complication indexes did not reach statistical significance in the RYGB group (all P>0.05). Conclusion:SG, RYGB, SADI-S and BPD/DS are all safe and effective treatments for super obesity. All of these procedures can improve the associated metabolic diseases to a certain extent.

Abstract Adverse childhood experiences (ACEs) not only affect individual s physical and mental health but also have adverse intergenerational effects. A growing body of researches focused on biological mechanism of ACEs, among which the emerging role of telomere has gained much attention. This article reviews the association between ACEs and telomere morphology during different developmental stages and the role of telomere in adverse health effects of ACEs. It aims to summarize possible mechanisms underlying negative effects of ACEs.