BackgroundAdolescents with depressive disorder often engage in non-suicidal self-injury （NSSI） behaviors， which severely impacts their physical and mental health. Impulsivity and emotional regulation are key factors influencing NSSI behaviors. However， research on the mechanisms through which impulsivity and emotional regulation affect NSSI behaviors in adolescent depressive disorder patients with NSSI remains insufficient， limiting the development of effective intervention strategies. ObjectiveTo explore the differences in impulsivity and emotion regulation abilities between adolescent patients with depressive disorder accompanied by and without NSSI behaviors， and to analyze the association between NSSI behaviors and impulsivity and emotion regulation abilities in adolescent patients with depressive disorder accompanied by NSSI behaviors. MethodsA total of 184 adolescents hospitalized in the child and adolescent psychiatry department of Wuxi Mental Health Center from October 2023 to August 2024， who met the diagnostic criteria for depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were consecutively enrolled as study subjects. Based on the diagnostic criteria for NSSI in DSM-5， patients were divided into NSSI group （n=108） and non-NSSI group （n=76）. The Barratt Impulsiveness Scale-11 （BIS-11）， the Emotion Regulation Questionnaire （ERQ）， the Adolescent Self-Harm Questionnaire， and the Positive and Negative Suicide Ideation （PANSI） were used for assessment. Spearman correlation analysis was employed to explore the correlation between the scores of the Adolescent Self-Harm Questionnaire and the scores of BIS-11 and ERQ in the NSSI group. Multiple regression analysis was conducted to examine the effects of impulsivity and emotion regulation on NSSI behaviors in the NSSI group. ResultsCompared to the non-NSSI group， the NSSI group showed significantly higher scores in BIS-11 non-planned impulsivity （Z=-4.181， P<0.05）， action impulsivity （t=4.944， P<0.05）， cognitive impulsivity （Z=-3.392， P<0.05）， and total score （t=4.763， P<0.05）， and lower scores in the cognitive reappraisal of ERQ （t=-4.094， P<0.05） and total score （Z=-2.299， P<0.05）， and higher scores in the expression inhibition of ERQ （Z=-3.019， P<0.05）. The correlation analysis results showed that the score of the adolescent self-harm questionnaire in the NSSI group was positively correlated with the behavioral impulsivity factor score in the BIS-11 （r=0.434， P<0.05）. Multiple regression analysis indicated that action impulsivity factor was a significant correlate of self-injury behaviors in the NSSI group （B=0.855， P<0.05）， explaining 22.30% of the total variance. ConclusionAdolescent patients with depressive disorder accompanied by NSSI behaviors exhibit higher levels of impulsivity and poorer emotional regulation abilities. Action impulsivity may play a significant role in the mechanism of NSSI behaviors. ［Funded by Wuxi Municipal Health Commission Research Project （number， Q202320）］

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

OBJECTIVE To investigate the in vitro activity of Chansu injection against SARS-CoV-2 infection and determine whether bufalin is the primary active component responsible for its efficacy.METHODS The half-maximal effective concentration(EC50)of Chansu injection and bufalin against SARS-CoV-2 infection was determined using the CellTiter-Glo cell viability assay.qPCR was performed to assess the effects of Chansu injection and bufalin on mRNA levels of SARS-CoV-2 NP protein,inflammatory factors,and interferons in virus-infected cells.A cell-cell membrane fusion model was established,and the impact of the drugs on membrane fusion between HEK-293T and HEK-293T-ACE2 cells was evaluated using a luciferase reporter gene assay.RESULTS Chansu injection exhibited anti-SARS-CoV-2 virus infection activity,with an EC50 of 85.56 ng·mL-1.Chansu injec-tion significantly reduced the mRNA levels of viral NP protein(P<0.05),IFN-λ2/3(P<0.05),ISG-15 and RIG-I(P<0.000 1)in SARS-CoV-2 infected Calu-3 cells,and the mRNA levels of inflammatory factors IL-6 and TNF-α were significantly reduced(P<0.000 1).The EC50 of bufalin in inhibiting SARS-CoV-2 virus-infected cells was 13.3 nmol·L-1,which might be the main active component of Chansu injection in resisting SARS-CoV-2 virus-infected cells.Chansu injection could significantly inhibit the cell membrane fusion mediated by the S protein of SARS-CoV-2 virus,thereby blocking the virus invasion.CONCLUSION Chansu injection demonstrates in vitro anti-SARS-CoV-2 activity by suppressing NP protein expression,reducing inflammatory cytokine lev-els,and blocking viral entry through membrane fusion inhibition.Bufalin is likely the key active component responsible for its anti-SARS-CoV-2 effects.

Inflammatory bowel disease (IBD) is an intestinal disease with uncertain etiology and complex mechanism. The interaction between environment and gene is a risk factor of IBD, which includes abnormal DNA methylation. In this review, we discuss the abnormal DNA methylation in IBD patients, and illustrate the interaction between gut microbiota and host through DNA methylation and its mechanism. Finally, we look forward to the prospect of regulating the interaction between gut microbiota and host through DNA methylation in the treatment of IBD.

Objective To investigate the effect of the use of glycopyrrolate before anesthesia on the perioperative circulation of patients undergoing laparoscopic cholecystectomy(LC).Methods 88 patients undergoing LC from March to June in 2024 were enrolled and randomly divided into two groups:the glycopyrrolate group(group G)and the control group(group C),with 44 patients in each.Three patients from group G and four from group C were excluded,leaving 41 patients in group G and 40 patients in group C.Ten minutes before anesthesia induction,group G received an intravenous dose of 4 μg/kg glycopyrrolate diluted to 5 mL with normal saline.The control group received an equal volume of normal saline.Both groups then received an intravenous infusion of dexmedetomidine at 1 μg/kg over 10 minutes.Heart rate(HR)and mean arterial pressure(MAP)were monitored immediately before infusion of glycopyrrolate/saline(T0),5 min after infusion(T1),10 min after infusion(T2),1 min after tracheal intubation(T3),immediately at skin incision(T4),2 min after pneumoperitoneum(T5),dissociating the cholecyst(T6),and 1 min after tracheal tube drawing(T7).Intraoperative amounts of propofol,rocuronium bromide,sufentanil,remifentanil,oral secretion score,PACU stay time,first postoperative flatus time and the occurrence of perioperative adverse reactions were observed.Results HR at T2,T3,T4,T5,and T6 time points was significantly higher in group G than in group C,while MAP at T1,T2,T3,T4,T5 time points was also significantly higher in group G(P<0.05).HR at T2 time points in Group G was significantly lower than that at T0,while T7 was significantly higher than that at T0 time points.In Group C,HR at T1,T2,T4,T5,and T6 time points was significantly lower than that at T0 time points,while T7 time points was significantly higher than that at T0 time points,with the differences being statistically significant(P<0.05).In Group G,MAP at T1 and T2 time pointswas significantly higher than that at T0,and MAP at T6 was significantly lower than that at T0 time points,and in Group C,MAP at T4,T5 and T6 time points was significantly lower than that at T0 time points,and the differences were all statistically significant(P<0.05);Oral secretion was lower in group G compared to group C,with a significant difference(P<0.05).The incidence of bradycardia was significantly lower in group G compared to group C(P<0.05).The incidence of oral dryness within 24 h postoperatively was higher in group G compared to group C(P<0.05).There were no significant differences of HR at T0,T1,and T7 time points,MAP at T0,T6,and T7 time points between the two groups(P>0.05);There were no significant differences of operation time,propofol usage,sufentanil usage,remifentanil usage,rocuronium bromide usage during operation,rate of atropine use,incidence of intraoperative hypotension,PACU stay time,first postoperative flatus,and nausea vomiting rate between the two groups(P>0.05);No delirium occurred in either group of patients 24 h after the operation.Conclusion Use of glycopyrrolate before anesthesia can be effectively applied to patients undergoing LC,is beneficial in reducing the incidence of bradycardia,maintaining the stability of intraoperative circulation,and has no significant effect on the incidence of postoperative delirium and nausea and vomiting.It is a worthy clinical application.

Objective:To investigate the clinical characteristics, postoperative complications, and risk factors for pouchitis in surgical patients with ulcerative colitis (UC).Methods:This was a retrospective observational study. The clinical data of 336 UC patients who had undergone surgical treatment at the Inflammatory Bowel Disease Center of the Department of General Surgery, Jinling Hospital Affiliated to Nanjing University Medical School from February 2014 to February 2024 were enrolled. The study patients were stratified into 2014-2019 ( n = 158) and 2020–2024 groups ( n = 178), these being the periods before and after biologics were covered for treatment of UC by national insurance in China in 2020. Clinical characteristics and surgical complications were analyzed and compared between the 2014-2019 and 2020-2024 groups. Multivariable logistic regression was performed to identify the risk factors associated with pouchitis in UC patients undergoing total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA). Results:The study cohort comprised 336 UC patients, 193 (57.4%) of whom were men. The median preoperative disease course was 48.0 months and the mean age at colectomy was 46.4±15.4 years. TPC-IPAA had been performed on 275 patients (81.8%), 129 in the 2014-2019 group and 146 in the 2020-2024 group. Sixty-one patients had undergone total or subtotal colectomy, 29 in the 2014-2019 group and 32 in the 2020-2024 group. 262 (78.0%) UC patients underwent surgery due to medical refractory. Ninety-nine (29.5%) had used biopharmaceuticals within 2 months prior to surgery, 63 (18.8%) of them having received infliximab. A smaller proportion of patients had undergone surgery for UC that was refractory to medications in the 2020–2024 group than in the 2014–2019 group (73.0% [130/178] vs. 83.5% [132/158], χ 2=5.384, P=0.020), the patients were older at colectomy (48.0±15.4 years vs. 44.6±15.2 years, t=-2.008, P=0.045), the body mass index was higher (20.2±3.1 kg/m 2 vs. 19.4±3.2 kg/m 2, t=-2.201, P=0.028), the Mayo score prior to surgery was lower ( M[ Q1, Q3]: 11.0 [9.2, 12.0 points] vs. 12.0 [11.0, 12.0) points, Z=-4.242, P=0.001), the rate of Charlson Comorbidity Index ≥ 3 scores was higher (27.0% [48/178] vs. 17.1% [27/158], χ 2=5.384, P=0.020), a greater percentage of patients had received biologics prior to surgery (41.0% [73/178) vs. 16.5% [26/158], χ 2=24.285, P<0.001), and intraoperative blood loss was greater ( M[ Q1, Q3]: 100.0 [100.0, 150.0] ml vs. 50.0 [30.0, 100.0] ml, Z=-7.054, P<0.001) despite the operation time being shorter (253.8±74.6 minutes vs. 315.2±96.8 minutes, t=6.265, P<0.001). Among the 275 patients undergoing TPC-IPAA, 95 (34.6%) had early complications (within 30 days after surgery), 20 (7.3%) of which were Clavien-Dindo Grade III–IV complications. Among these patients, 50 (18.2%) had ileus or small bowel obstruction, 11 in the 2014-2019 group and 39 in the 2020-2024 group; this difference is statistically significant (χ 2=15.225, P<0.001). Ninety-one patients (33.1%) had late complications (more than 30 days after surgery), 75 (27.3%) being pouchitis (36 in the 2014-2019 group and 39 in the 2020-2024 group); this difference is not statistically significant (χ 2=0.049, P=0.824). Five patients (1.8%) had undergone pouch excision with permanent ileostomy. Among the 61 patients who had undergone total or subtotal colectomy, 26 (42.6%) developed early postoperative complications, including 10 (16.4%) Clavien-Dindo Grade III-IV complications and one death (1.6%), the last being attributable to multiorgan dysfunction. Three patients (4.9%) had late complications; the difference in incidence of postoperative complications between the 2014-2019 and 2020-2024 groups is not statistically significant (both P>0.05). Multivariable analysis identified intraoperative blood transfusion (OR: 2.12, 95% CI: 1.19–3.75, P=0.010) and interval to stoma closure > 120 days (OR: 2.05, 95%CI: 1.16-3.62, P = 0.013) as independent risk factors for development of pouchitis in UC patients undergoing TPC-IPAA. Conclusion:Surgical treatment of UC remains safe in the biologics era. Proactive strategies to reduce intraoperative blood transfusion and achieve timely stoma closure may reduce the risk of pouchitis in UC patients undergoing TPC-IPAA.

Objective To investigate the effect of the use of glycopyrrolate before anesthesia on the perioperative circulation of patients undergoing laparoscopic cholecystectomy(LC).Methods 88 patients undergoing LC from March to June in 2024 were enrolled and randomly divided into two groups:the glycopyrrolate group(group G)and the control group(group C),with 44 patients in each.Three patients from group G and four from group C were excluded,leaving 41 patients in group G and 40 patients in group C.Ten minutes before anesthesia induction,group G received an intravenous dose of 4 μg/kg glycopyrrolate diluted to 5 mL with normal saline.The control group received an equal volume of normal saline.Both groups then received an intravenous infusion of dexmedetomidine at 1 μg/kg over 10 minutes.Heart rate(HR)and mean arterial pressure(MAP)were monitored immediately before infusion of glycopyrrolate/saline(T0),5 min after infusion(T1),10 min after infusion(T2),1 min after tracheal intubation(T3),immediately at skin incision(T4),2 min after pneumoperitoneum(T5),dissociating the cholecyst(T6),and 1 min after tracheal tube drawing(T7).Intraoperative amounts of propofol,rocuronium bromide,sufentanil,remifentanil,oral secretion score,PACU stay time,first postoperative flatus time and the occurrence of perioperative adverse reactions were observed.Results HR at T2,T3,T4,T5,and T6 time points was significantly higher in group G than in group C,while MAP at T1,T2,T3,T4,T5 time points was also significantly higher in group G(P<0.05).HR at T2 time points in Group G was significantly lower than that at T0,while T7 was significantly higher than that at T0 time points.In Group C,HR at T1,T2,T4,T5,and T6 time points was significantly lower than that at T0 time points,while T7 time points was significantly higher than that at T0 time points,with the differences being statistically significant(P<0.05).In Group G,MAP at T1 and T2 time pointswas significantly higher than that at T0,and MAP at T6 was significantly lower than that at T0 time points,and in Group C,MAP at T4,T5 and T6 time points was significantly lower than that at T0 time points,and the differences were all statistically significant(P<0.05);Oral secretion was lower in group G compared to group C,with a significant difference(P<0.05).The incidence of bradycardia was significantly lower in group G compared to group C(P<0.05).The incidence of oral dryness within 24 h postoperatively was higher in group G compared to group C(P<0.05).There were no significant differences of HR at T0,T1,and T7 time points,MAP at T0,T6,and T7 time points between the two groups(P>0.05);There were no significant differences of operation time,propofol usage,sufentanil usage,remifentanil usage,rocuronium bromide usage during operation,rate of atropine use,incidence of intraoperative hypotension,PACU stay time,first postoperative flatus,and nausea vomiting rate between the two groups(P>0.05);No delirium occurred in either group of patients 24 h after the operation.Conclusion Use of glycopyrrolate before anesthesia can be effectively applied to patients undergoing LC,is beneficial in reducing the incidence of bradycardia,maintaining the stability of intraoperative circulation,and has no significant effect on the incidence of postoperative delirium and nausea and vomiting.It is a worthy clinical application.

Inflammatory bowel disease (IBD) is an intestinal disease with uncertain etiology and complex mechanism. The interaction between environment and gene is a risk factor of IBD, which includes abnormal DNA methylation. In this review, we discuss the abnormal DNA methylation in IBD patients, and illustrate the interaction between gut microbiota and host through DNA methylation and its mechanism. Finally, we look forward to the prospect of regulating the interaction between gut microbiota and host through DNA methylation in the treatment of IBD.

OBJECTIVE To investigate the in vitro activity of Chansu injection against SARS-CoV-2 infection and determine whether bufalin is the primary active component responsible for its efficacy.METHODS The half-maximal effective concentration(EC50)of Chansu injection and bufalin against SARS-CoV-2 infection was determined using the CellTiter-Glo cell viability assay.qPCR was performed to assess the effects of Chansu injection and bufalin on mRNA levels of SARS-CoV-2 NP protein,inflammatory factors,and interferons in virus-infected cells.A cell-cell membrane fusion model was established,and the impact of the drugs on membrane fusion between HEK-293T and HEK-293T-ACE2 cells was evaluated using a luciferase reporter gene assay.RESULTS Chansu injection exhibited anti-SARS-CoV-2 virus infection activity,with an EC50 of 85.56 ng·mL-1.Chansu injec-tion significantly reduced the mRNA levels of viral NP protein(P<0.05),IFN-λ2/3(P<0.05),ISG-15 and RIG-I(P<0.000 1)in SARS-CoV-2 infected Calu-3 cells,and the mRNA levels of inflammatory factors IL-6 and TNF-α were significantly reduced(P<0.000 1).The EC50 of bufalin in inhibiting SARS-CoV-2 virus-infected cells was 13.3 nmol·L-1,which might be the main active component of Chansu injection in resisting SARS-CoV-2 virus-infected cells.Chansu injection could significantly inhibit the cell membrane fusion mediated by the S protein of SARS-CoV-2 virus,thereby blocking the virus invasion.CONCLUSION Chansu injection demonstrates in vitro anti-SARS-CoV-2 activity by suppressing NP protein expression,reducing inflammatory cytokine lev-els,and blocking viral entry through membrane fusion inhibition.Bufalin is likely the key active component responsible for its anti-SARS-CoV-2 effects.