Objective:To evaluate the role of autophagy in reduction of high glucose and hypoxia-reoxygenation (HG+ H/R) injury to isolated cardiomyocytes by dexmedetomidine in rats.Methods:The normally cultured rat H9c2 cardiomyocytes at the logarithmic growth phase were seeded in 6-well plates at a density of 1×10 6 cells/ml and divided into 4 groups ( n=15 each) using a random number table method: control group (group C), group HG+ H/R, dexmedetomidine group (group DEX) and dexmedetomidine+ autophagy inhibitor 3-methylpurine group (group 3-MA). The cells were incubated in culture medium with 1% fetal bovine serum + 1% double antibody for 24 h when the cell density reached 50%.To establish HG+ H/R injury model, the cardiomyocytes were cultured in high-glucose culture medium (glucose concentration of 33 mmol/L) for 24 h, and then incubated in a 37 ℃ incubator (95% N 2+ 5%CO 2) for 4 h followed by reoxygenation (90%O 2+ 10%CO 2) for 2 h. Dexmedetomidine was added until the final concentration reached 5 μmol/L at 1 h before hypoxia in DEX and 3-MA groups, and 3-MA was added until the final concentration reached 5 μmol/L at 1 h of incubation with dexmedetomidine.At 2 h after reoxygenation, the cell viability was recorded by the cell counting kit-8 assay, lactate dehydrogenase (LDH) activity was detected by LDH kit, the expression of autophagy-related protein LC3, P62 and Beclin-1 was detected by Western Blot, the ratio of LC3Ⅱ/LC3Ⅰwas calculated, and the expression of P62 and Beclin-1 mRNA was detected by real-time polymerase chain reaction. Results:Compared with group C, the cell viability was significantly decreased in HG+ H/R, DEX and 3-MA groups, LDH activity in the supernatant was increased and expression of P62 was decreased in HG+ H/R and 3-MA groups, ratio of LC3Ⅱ/LC3Ⅰwas decreased in group 3-MA, and the expression of Beclin-1 was down-regulated in group HG+ H/R ( P<0.05). Compared with HG+ H/R group, LDH activity in the supernatant was significantly decreased, expression of Beclin-1, P62 and its mRNA was up-regulated, and ratio of LC3Ⅱ/LC3Ⅰwas increased in DEX group, and LDH activity in the supernatant was increased in group 3-MA ( P<0.05). Compared with DEX group, cell viability were decreased, LDH activity in the supernatant was increased, Beclin-1, P62 and its mRNA was down-regulated, and ratio of LC3Ⅱ/ LC3Ⅰwas decreased in group 3-MA ( P<0.05). Conclusion:Autophagy is involved in the reduction of HG+ H/R injury to isolated cardiomyocytes by dexmedetomidine in rats.

ObjectiveTo study the surgical treatment of large bowel obstruction caused by colorectal carcinoma.MethodsRetrospective analysis of the experience of surgical treatment for the large bowel obstruction caused by colorectal carcinoma in 52 patients from 1995 to 1999 was performed. ResultsIn the 52 patients, the right hemnicolectomy was performed in 9 patients; left hemicolectomy with proximal colon fistulization was performed in 37patients;transvercolectomy was performed in 4 patients; sigmoid fistulization was performed in 2 patients for their rectum carcinoma couldn't be resected. The postoperative complication rate was 15.3%(8/52),and perioperative mortality rate was 3.8%(2/52). Conclusion More attention should be paid to large bowel obstruction caused by colorectal carcinoma. Selecting rational colectomy and appropriate perioperative management is important for reducing both complication and mortality rate.

Objective To prepare and study the immunogenicity of hepatitis B virus surface anti-gen (HBsAg)-tetanus toxoid (TT) conjugate vaccine. Methods Tr was activated by cyangen bromide and reacted with adipic acid dihydrazide, then HBsAg-TT conjugate was prepared by carbediimide. Conjugate, HBsAg or hepatitis B vaccine was injected subcutaneously into mice. Anti-HBsAg and HBsAg-specific T cell response elicited by these immunogens were assayed. Results New HBsAg-TT conjugate elicited higher levels of anti-HBsAg and HBsAg positive conversion rates after the immunization than did HBsAg alone or hepatitis B vaccine. Conjugate induced mesdy antibodies of the IgG2a subclass, while HBsAg alone or hepa-titis B vaccine mainly elicited anti-HBsAg in the IgG1 subclass. The number of IFN-γand IL-2 secreting T cells induced by conjugate was also significantly higher than that did by HBsAg or hepatitis B vaccine. Con-clusion This study indicated new HBsAg-TT conjugate can induce both stronger humoral and TH1 type of cellular immune response.

Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have recently been identified. Here, we report the requirement of gluconate 5-dehydrogenase (Ga5DH) in cell division of the zoonotic pathogen Streptococcus suis. Ga5DH catalyzes the reversible reduction of 5-ketogluconate to D-gluconate and was localized to the site of cell division. The deletion of Ga5DH in S. suis resulted in a plump morphology with aberrant septa joining the progeny. A significant increase was also observed in cell length. These defects were determined to be the consequence of Ga5DH deprivation in S. suis causing FtsZ delocalization. In addition, the interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction assays. These results indicate that Ga5DH may function to prevent the formation of ectopic Z rings during S. suis cell division.
Bacterial Proteins ; chemistry ; genetics ; metabolism ; Cell Division ; Cell Shape ; Cytoskeletal Proteins ; chemistry ; genetics ; metabolism ; Mutation ; Oxidoreductases ; deficiency ; genetics ; metabolism ; Protein Binding ; Streptococcus suis ; enzymology

BackgroundThe major depressive disorder has high prevalence among adolescents， and non-suicidal self-injury （NSSI） behaviors frequently occur among patients， therefore， major depressive disorder in adolescents has become the researching focus. ObjectiveTo explore the effect of mentalization-based family therapy （MBFT） on depressive symptoms and NSSI behavior in adolescents with major depressive disorder， and to provide references for the rehabilitation of major depressive disorder in adolescents. MethodsA total of 90 adolescent patients with major depression disorder who met the diagnostic criteria of International Classification of Diseases， 10th edition （ICD-10） for depressive disorders and attended Wuhan Mental Health Center from January to December 2022 were selected， and were assigned into study group （n=44） and control group （n=46） using random number table method. All participants received routine intervention， based on this， study group added a 60-minute MBFT intervention once a week for 8 weeks. Before the intervention and at the end of 1^st， 2^nd，4^th and 8^th week，the two groups were assessed using Hamilton Depression Scale-24 item （HAMD-24）， General Self-Efficacy Scale （GSES）， Pittsburgh Sleep Quality Index （PSQI） and Ottawa Self-injury Inventory （OSI）. ResultsThe repeated measures analysis of variance reported a statistical main effect of time， main effect of group， and interaction effect between time and group at the baseline and the end of 1^st， 2^nd， 4^th and 8^th week of treatment in HAMD-24 score （F=69.621， 15.428， 29.623， P˂0.05）， OSI score （F=176.642， 37.682， 21.873， P˂0.05）， GSES score （F=215.236， 57.421， 27.857， P˂0.05） and PSQI score （F=268.541， 61.863， 33.867， P˂0.05）. Individual effect analysis discovered a statistical difference between study group and control group at the end of 2^nd， 4^th and 8^th week of treatment in HAMD-24 score （t=5.567， 8.645， 6.233， P˂0.01）， OSI score （t=3.675， 11.817， 9.632， P˂0.01）， GSES score （t=23.462， 31.709， 12.750， P˂0.01） and PSQI score （t=9.664， 22.457， 9.333， P˂0.01）. ConclusionMBFT may improve depressive symptoms， NSSI behavior， sleep quality and self-efficacy in adolescents with major depressive disorder. ［Funded by 2022 Natural Science Foundation Project of Hubei Province （number， 2022CFB483）］

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.