Objective:To investigate the interplay between childhood traumatic experiences,mental disorders,and cognitive function among patients with alcohol use disorder(AUD).Methods:A cross-sectional study was con-ducted involving 160 patients with AUD hospitalized in the department of alcohol dependence.They were catego-rized into three groups based on their symptoms,namely the simple alcohol dependence group(AD group,n=86),the alcohol dependence with hallucinatory delusion group(ADHD group,n=43),and the alcohol dependence with delirium tremens group(ADDT group,n=31).The adverse childhood experiences,cognitive function,and child-hood trauma were assessed with the Adverse Childhood Experiences International Questionnaire(ACE-IQ),Mont-real Cognitive Assessment(MoCA),and Childhood Trauma Questionnaire(CTQ-SF).Results:The MoCA scores were significantly higher in the AD group than in the ADHD and ADDT groups[21.0(19.0,23.0)vs.19.0(15.0,22.0)vs.18.0(16.0,22.0),P＜0.01].The ADDT group had higher sexual abuse scores of CTQ-SF than the AD group.Lower MoCA score was associated with hallucination and delusion(OR=0.82,P＜0.01)or deliri-um tremens(OR=0.81,P＜0.01)in AUD patients.Higher ACE-IQ score was associated with hallucination and delusion in AUD patients(OR=1.51,P＜0.01).Conclusion:Mostpatients with alcohol use disorder have child-hood trauma and cognitive dysfunction.Poor cognitive function and adverse childhood experiences are risk factors for mental disorders among patients with alcohol use disorder.

Objective:To explore the relationship between depression, perfectionism and self-injurious function in adolescents with self-injury.Methods:A total of 6 149 adolescents from two middle schools were selected by multi-stage random sampling method to conduct a cross-sectional investigation, and 530 cases with self-injurious behaviors were screened out as the self-injury group, while the remaining 5 619 students served as the non-self-injury group.The self-rating depression scale, the Chinese-revised Frost multidimensional perfectionism scale, and the Ottawa self-injury inventory Chinese revised version were used for investigation.SPSS 24.0 software was used for descriptive statistics and Spearman correlation analysis, and the PROCESS 4.1 macro program was used for mediating effect test(model 4)and moderating effect test(model 7).Results:(1)The incidence of self-injury among adolescents was 8.62%(530/6 149), which was significantly different in gender( χ2=50.942, P<0.01) and grade( χ2=37.401, P<0.01). (2)The scores of depression(48(41, 55)) and maladaptive perfectionism(64(53, 76)) in the self-injury group were higher than those in the non-self-injury group(36(29, 43), 49(35, 61)), and the differences were statistically significant( Z=-23.233, -18.599, both P<0.01). (3)Adolescents with self-injury mostly had external emotion regulation(70.38%(373/530)) as the dominant function.(4)The results of Spearman correlation analysis showed that self-injurious function was significantly and positively correlated with depression( r=0.382, P<0.01) and maladaptive perfectionism( r=0.356, P<0.01), and depression was significantly and positively correlated with maladaptive perfectionism( r=0.352, P<0.01). (5)Maladaptive perfectionism partially mediated the relationship between depression and self-injurious function( β=0.086, P<0.001), and the mediating effect accounted for 21.88%(0.086/0.393)of the total effect.(6)Gender moderated the first stage of the mediation pathway(depression→maladaptive perfectionism)( β=0.180, P<0.05), which indicated that depression had a stronger predictive effect on maladaptive perfectionism in women( βsimple=0.105, 95% CI=0.063-0.154, P<0.05). Conclusion:In the prediction of depression on self-injurious function, maladaptive perfectionism plays a partial mediating role, and this mediating effect is moderated by gender.

Iatrogenic bile duct injury(IBDI)is a common type of bile duct injury,most frequently occurring during cholecystectomy.With the widespread use of laparoscopic cholecystectomy,its incidence is significantly higher than that of open surgery,and the number of complex cases combined with vascular injury(VI)has been increasing,posing greater challenges for diagnosis and treatment.In severe cases,it may result in hepatic ischemia and atrophy.Hepaticojejunostomy is the standard reconstructive procedure after bile duct injury,whereas hepatectomy may be required when VI is involved.We report the case of a 53-year-old woman who was admitted with bile leakage following cholecystectomy.After two multidisciplinary team(MDT)discussions,preoperative evaluation revealed injury to the right hepatic artery and a portal vein branch,accompanied by atrophy of the right anterior lobe.Based on intraoperative findings,the patient underwent right hepatectomy combined with Roux-en-Y hepaticojejunostomy of the left hepatic duct.Postoperative recovery was uneventful,and the patient remained symptom-free during a 6-month follow-up.By reviewing the diagnosis and management of this case in conjunction with relevant literature,we summarize the clinical features,treatment strategies,and the value of MDT management in complex IBDI,aiming to provide reference for clinical practice.

Iatrogenic bile duct injury(IBDI)is a common type of bile duct injury,most frequently occurring during cholecystectomy.With the widespread use of laparoscopic cholecystectomy,its incidence is significantly higher than that of open surgery,and the number of complex cases combined with vascular injury(VI)has been increasing,posing greater challenges for diagnosis and treatment.In severe cases,it may result in hepatic ischemia and atrophy.Hepaticojejunostomy is the standard reconstructive procedure after bile duct injury,whereas hepatectomy may be required when VI is involved.We report the case of a 53-year-old woman who was admitted with bile leakage following cholecystectomy.After two multidisciplinary team(MDT)discussions,preoperative evaluation revealed injury to the right hepatic artery and a portal vein branch,accompanied by atrophy of the right anterior lobe.Based on intraoperative findings,the patient underwent right hepatectomy combined with Roux-en-Y hepaticojejunostomy of the left hepatic duct.Postoperative recovery was uneventful,and the patient remained symptom-free during a 6-month follow-up.By reviewing the diagnosis and management of this case in conjunction with relevant literature,we summarize the clinical features,treatment strategies,and the value of MDT management in complex IBDI,aiming to provide reference for clinical practice.

This study aims to determine the nephrotoxic effects of 3-monochloropropanel-1,2-diol(3-MCPD)on female and male SD rats.A nephrotoxicity model was established by gavage of dif-ferent doses of 3-MCPD,and 80 SD rats were randomly divided into four groups:the control group(0 mg/kg 3-MCPD),low-dose group(15 mg/kg 3-MCPD),medium-dose group(30 mg/kg 3-MCPD),high-dose group(60 mg/kg 3-MCPD),with half female and half male.The body mass and food intake of the rats were recorded weekly,and the urine and blood and kidney tissues were col-lected after 28 consecutive days of gavage,and the blood erythrocyte count(WBC),white blood cell count(RBC),hemoglobin(HGB),erythrocyte-compaction-transfer-value(HCT),creatinine(CREA),serum urea nitrogen(BUN),and the indexes of blood phosphorus(P)and calcium(Ca)were detected;the level of kidney injury molecule(KIM-1)was measured by ELISA kit;the renal pathological changes was observed by histopathology method;and transcriptome sequencing was used to analyze differential genes in female and male rats.The results showed that 3-MCPD did not significantly affect the growth of male rats,but high doses significantly reduced the weight and food intake of female rats.The high-dose group of 3-MCPD caused a significant decrease in RBC,HGB,and HCT levels in both male and female rats,resulting in a significant increase in KIM-1 and P,and a significant decrease in Ca,but only a significant increase in CREA and BUN in female rats.Histopathology showed that in the high-dose group of male rats,only mild renal tubular dilation,epithelial cell edema,and clear tubular type were observed in the kidneys,while in female rats,a large number of renal sacs,clear tubular type,and interstitial inflammatory cells with fibrosis were observed in the kidneys.Transcriptome sequencing showed 1 712 differentially expressed genes in the high-dose group of female rats and 1 153 differentially expressed genes in the high-dose group of male rats.KEGG enrichment analysis showed that both male and female rats in the high-dose group experienced oxidative stress and cell apoptosis,but 3-MCPD may also participate in the process of kidney damage in females by inhibiting autophagy and inducing iron death pathways.The above results indicate that high-dose 3-MCPD has a more significant nephrotoxic effect on fe-male rats.

Objective:To explore the relationship between depression, perfectionism and self-injurious function in adolescents with self-injury.Methods:A total of 6 149 adolescents from two middle schools were selected by multi-stage random sampling method to conduct a cross-sectional investigation, and 530 cases with self-injurious behaviors were screened out as the self-injury group, while the remaining 5 619 students served as the non-self-injury group.The self-rating depression scale, the Chinese-revised Frost multidimensional perfectionism scale, and the Ottawa self-injury inventory Chinese revised version were used for investigation.SPSS 24.0 software was used for descriptive statistics and Spearman correlation analysis, and the PROCESS 4.1 macro program was used for mediating effect test(model 4)and moderating effect test(model 7).Results:(1)The incidence of self-injury among adolescents was 8.62%(530/6 149), which was significantly different in gender( χ2=50.942, P<0.01) and grade( χ2=37.401, P<0.01). (2)The scores of depression(48(41, 55)) and maladaptive perfectionism(64(53, 76)) in the self-injury group were higher than those in the non-self-injury group(36(29, 43), 49(35, 61)), and the differences were statistically significant( Z=-23.233, -18.599, both P<0.01). (3)Adolescents with self-injury mostly had external emotion regulation(70.38%(373/530)) as the dominant function.(4)The results of Spearman correlation analysis showed that self-injurious function was significantly and positively correlated with depression( r=0.382, P<0.01) and maladaptive perfectionism( r=0.356, P<0.01), and depression was significantly and positively correlated with maladaptive perfectionism( r=0.352, P<0.01). (5)Maladaptive perfectionism partially mediated the relationship between depression and self-injurious function( β=0.086, P<0.001), and the mediating effect accounted for 21.88%(0.086/0.393)of the total effect.(6)Gender moderated the first stage of the mediation pathway(depression→maladaptive perfectionism)( β=0.180, P<0.05), which indicated that depression had a stronger predictive effect on maladaptive perfectionism in women( βsimple=0.105, 95% CI=0.063-0.154, P<0.05). Conclusion:In the prediction of depression on self-injurious function, maladaptive perfectionism plays a partial mediating role, and this mediating effect is moderated by gender.

Objective:To investigate the interplay between childhood traumatic experiences,mental disorders,and cognitive function among patients with alcohol use disorder(AUD).Methods:A cross-sectional study was con-ducted involving 160 patients with AUD hospitalized in the department of alcohol dependence.They were catego-rized into three groups based on their symptoms,namely the simple alcohol dependence group(AD group,n=86),the alcohol dependence with hallucinatory delusion group(ADHD group,n=43),and the alcohol dependence with delirium tremens group(ADDT group,n=31).The adverse childhood experiences,cognitive function,and child-hood trauma were assessed with the Adverse Childhood Experiences International Questionnaire(ACE-IQ),Mont-real Cognitive Assessment(MoCA),and Childhood Trauma Questionnaire(CTQ-SF).Results:The MoCA scores were significantly higher in the AD group than in the ADHD and ADDT groups[21.0(19.0,23.0)vs.19.0(15.0,22.0)vs.18.0(16.0,22.0),P＜0.01].The ADDT group had higher sexual abuse scores of CTQ-SF than the AD group.Lower MoCA score was associated with hallucination and delusion(OR=0.82,P＜0.01)or deliri-um tremens(OR=0.81,P＜0.01)in AUD patients.Higher ACE-IQ score was associated with hallucination and delusion in AUD patients(OR=1.51,P＜0.01).Conclusion:Mostpatients with alcohol use disorder have child-hood trauma and cognitive dysfunction.Poor cognitive function and adverse childhood experiences are risk factors for mental disorders among patients with alcohol use disorder.

This study aims to determine the nephrotoxic effects of 3-monochloropropanel-1,2-diol(3-MCPD)on female and male SD rats.A nephrotoxicity model was established by gavage of dif-ferent doses of 3-MCPD,and 80 SD rats were randomly divided into four groups:the control group(0 mg/kg 3-MCPD),low-dose group(15 mg/kg 3-MCPD),medium-dose group(30 mg/kg 3-MCPD),high-dose group(60 mg/kg 3-MCPD),with half female and half male.The body mass and food intake of the rats were recorded weekly,and the urine and blood and kidney tissues were col-lected after 28 consecutive days of gavage,and the blood erythrocyte count(WBC),white blood cell count(RBC),hemoglobin(HGB),erythrocyte-compaction-transfer-value(HCT),creatinine(CREA),serum urea nitrogen(BUN),and the indexes of blood phosphorus(P)and calcium(Ca)were detected;the level of kidney injury molecule(KIM-1)was measured by ELISA kit;the renal pathological changes was observed by histopathology method;and transcriptome sequencing was used to analyze differential genes in female and male rats.The results showed that 3-MCPD did not significantly affect the growth of male rats,but high doses significantly reduced the weight and food intake of female rats.The high-dose group of 3-MCPD caused a significant decrease in RBC,HGB,and HCT levels in both male and female rats,resulting in a significant increase in KIM-1 and P,and a significant decrease in Ca,but only a significant increase in CREA and BUN in female rats.Histopathology showed that in the high-dose group of male rats,only mild renal tubular dilation,epithelial cell edema,and clear tubular type were observed in the kidneys,while in female rats,a large number of renal sacs,clear tubular type,and interstitial inflammatory cells with fibrosis were observed in the kidneys.Transcriptome sequencing showed 1 712 differentially expressed genes in the high-dose group of female rats and 1 153 differentially expressed genes in the high-dose group of male rats.KEGG enrichment analysis showed that both male and female rats in the high-dose group experienced oxidative stress and cell apoptosis,but 3-MCPD may also participate in the process of kidney damage in females by inhibiting autophagy and inducing iron death pathways.The above results indicate that high-dose 3-MCPD has a more significant nephrotoxic effect on fe-male rats.

Objective This study investigated the protective effects of Corni Fructus ethanol extract on β-amyloid protein 25-35 (Aβ25-35)-induced Alzheimer's disease (AD) mice by regulating histone lysine-specific demethylase 1 (LSD1) / postsynaptic density protein 95 (PSD95) on synapses and neuroinflammation. Methods Specifically, according to the body weight, 40 C57BL/6N mice were randomized into four groups: the sham operation group, the model group, the low-dose (0.1mg/g) and the high-dose (0.3 mg/g) Corni Fructus ethanol extract groups. Aβ25-35 was injected into the hippocampus of mice in three groups except for the sham operation group to established AD model. All mice were orally administered with either Corni Fructus ethanol extract or vehicle by gavage for 7 days before molding and continued 5 days after surgery for a total of 60 days. Morris water maze, Y maze and open field tests were performed to evaluate the recognition memory and space exploration ability of mice. The expression of LSD1, PSD95, synaptophysin (SYN), interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α) and H3K9me2 level were measured by Western blotting. Chromatin immunoprecipitation (CHIP) combined with qPCR was used to detect H3K9me2 modification of PSD95 promoter region and mRNA levels of PSD95. The correlation between the expression of H3K9me2 and PSD95 and the expression of IBA1 in the hippocampus were detected by immunofluorescence assay.Results The result showed that Corni Fructus ethanol extract significantly reversed Aβ25-35-induced learning and memory impairment in AD mice. Compared with the model group, Corni Fructus ethanol extract demonstrated shorter escape latency, increased number and time of autonomous activities and the rate of autonomous alternation. Moreover, it increased the expression of LSD1 in hippocampus of AD mice(P<0.05), and reduced H3K9me2 modification level in the promoter region of PSD95 gene, and then promoted the mRNA transcription and protein expression of PSD95. Immunofluorescence staining indicated the reduction of H3K9me2 modification level in hippocampus was accompanied by the enhancement of PSD95 expression. Corni Fructus ethanol extract could also inhibit the activation of microglia and reduce the expression of proinflammatory factors IL-1β and TNF-α.Conclusion Corni Fructus ethanol extract may regulate PSD95 gene transcription by up-regulating the expression of LSD1 and reducing the H3K9me2 modification level in its promoter region, thereby increasing the expression of PSD95, a key protein in synaptic plasticity regulation, which alleviate neuroinflammatory response, improve learning and memory dysfunction in AD model mice, and thus play a protective role in Aβ25-35-induced nerve damage.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.