The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective:To investigate the lipidomics differences of CD4+T immune cells in diabetic kidney disease(DKD)mice,and screen out the differential metabolites with biological significance.Methods:CD4(L3T4)MicroBeads immunomagnetic beads were used to isolate CD4+T immune cells from spleen of BKS.Cg-Dock7m+/+Leprdb/J mice with spontaneous DKD;the purity of CD4+T cells were identified by flow cytometry.The non-targeted lipidomics of CD4+T cells were detected by LC-MS/MS,and the differ-ential metabolites were analyzed.Results:A total of 463 metabolites were detected by LC-MS.PCA and OPLS-DA analysis showed that the metabolic components were significantly separated;twenty-four differential metabolites were screened out.KEGG and enrich-ment analysis showed that the differential metabolites involved in the disorder of glycerol phospholipid metabolism.Conclusion:Phos-pholipid metabolism of CD4+T cells is closely related to the occurrence of DKD.Phospholipid metabolism targeting DKD CD4+T cells in DKD may be a new direction of DKD treatment.

Objective:To analyze factors associated with timely vaccination of pertussis-containing vaccines in children born in Shanghai from 2019 to 2023.Methods:Children born in Shanghai between 2019 and 2023 were selected using a stratified random sampling method, and their vaccination data were obtained from the Shanghai Vaccine Management and Vaccination Service Information System. The vaccination rates, timely vaccination rates, and the proportions of diphtheria-tetanus-acellular pertussis-haemophilus influenzae type b combination vaccine (DTaP-Hib) and diphtheria-tetanus-acellular pertussis-inactivated poliovirus-haemophilus influenzae type b combination vaccine (DTaP-IPV-Hib) for the substitution of diphtheria- tetanus-acellular pertussis vaccine (DTaP) were calculated. Also, the factors associated with timely vaccination rate was analyzed with multivariate logistic regression analysis.Results:The average vaccination coverage rate of pertussis-containing vaccines in children born in Shanghai from 2019 to 2023 ranged from 94.71% to 99.53%. There were significant differences in the vaccination coverage of the 1 st-4 th doses of pertussis-containing vaccines among children born in different years (all P<0.05), but no gender and area specific significant differences were observed (all P>0.05). Non-national immunization program (non-NIP) vaccines were used to substitute DTaP vaccines in some children, with the proportion of DTaP-IPV-Hib vaccine accounting for 50.11%-52.69% and the proportion of DTaP-Hib vaccine accounting for 27.22%-28.43%. The proportions of DTaP-Hib and DTaP-IPV-Hib for the substitution of DTaP had increasing trends over the years. The overall timely vaccination rate of pertussis-containing vaccine vaccination was 84.09%. Analysis on the factors affecting the timely vaccination rate showed that the rate gradually decreased with the increase of the doses. Children who received the self-paid quadrivalent or pentavalent vaccines were less likely to have vaccination delays. Birth year had a significant impact on the timely vaccination rate, while the area had less impact. Additionally, the timely vaccination rate was also influenced by the degree of non-pharmaceutical intervention measures. Conclusions:The substitution of pertussis- containing vaccines with non-NIP vaccines was common in Shanghai. The coverage and timeliness of pertussis-containing vaccine vaccination were relatively high. The timely vaccination rate was significantly associated with gender, dose, vaccine type, and the degree of non-pharmaceutical interventions. There was a certain proportions of delayed and missed vaccinations, and it is necessary to pay attention to children who are not vaccinated timely and conduct high-quality catch-up vaccination to ensure timely and complete vaccination of pertussis-containing vaccines.

AIM: Previous studies have suggested that big stick design (BSD) method can only be used in clinical trials of two treatments with equal proportion, which has good statistical performance and has become the recommended choice of randomized methods. This study expands BSD method, so that it can be applied to three groups, and provides more randomized methods for clinical trials. METHODS: On the basis of BSD method used in two treatments with equal proportion, the derivation conditional allocation probability of BSD method used in three treatments with equal proportion was carried out. BSD method was compared with simple randomization (SR) method, permuted block design (PBD) method and block urn design (BUD) method by Monte-Carlo simulation in balance and randomness. RESULTS: In terms of balance, PBD method was the best, followed by BUD method, BSD method, and SR method was the worst. In terms of randomness, SR method was the best, followed by BSD method, BUD method and PBD method. The comprehensive performance showed that BSD method was better than BUD method, PBD method and SR method. CONCLUSION: The expanded BSD method used in three treatments with equal proportion has good comprehensive performance, and it can be the recommended randomization method for clinical trials of three treatments with equal proportion.

Objective:To explore the status of quality of sexual life, self-acceptance and self-disclosure in patients with breast cancer undergoing chemotherapy after surgery, and analyze the mediating effect of self-disclosure between self-acceptance and quality of sexual life.Methods:Using convenience sampling, 209 female patients with breast cancer undergoing postoperative chemotherapy in a Class Ⅲ Grade A hospital in Zhuhai from January to October 2022 were selected for investigation by using the General Information Questionnaire, Sexual Quality of Life Questionnaire for Breast Cancer Survivors, Self-Acceptance Questionnaire (SAQ) and Distress Disclosure Index (DDI). Pearson correlation was used to analyze the correlation between quality of sexual life, self-acceptance and self-disclosure in breast cancer patients undergoing chemotherapy after surgery. Bootstrap mediating effect method was used to analyze the mediating effect of self-disclosure between self-acceptance and quality of sexual life in breast cancer patients undergoing chemotherapy after surgery.Results:The scores of the quality of sexual life (average score of items), self-acceptance and self-disclosure of breast cancer patients undergoing chemotherapy after surgery were (2.69±0.59), (38.61±5.32) and (35.90±5.73) respectively. The quality of sexual life of patients was positively correlated with self-acceptance and self-disclosure, and self-acceptance had a mediating effect on the quality of sexual life through self-disclosure ( P<0.05) . Conclusions:The quality of sexual life of breast cancer patients undergoing chemotherapy after surgery needs to be improved. Helping patients increase their self-acceptance and self-disclosure level will help them improve their quality of sexual life.

Objective:To explore the teaching effect of individualized teaching based on problem-based learning (PBL) that applied in gynecology practice teaching under the background of conflicts between postgraduate examination preparation and clinical internship for medical undergraduates.Methods:A total of 157 medical students of the five-year program who started gynecology internship and meanwhile prepared for the postgraduate entrance examination in 2018 were enrolled in the study and divided into two groups randomly. One group received traditional teaching (control group), and the other group received individualized teaching mode based on PBL (observation group). After the internship, the two groups of students were assessed for their theoretical and clinical skills, and the students' evaluation of the teaching effect was acquired through a questionnaire survey. SPSS 22.0 was used to perform chi-square test.Results:The students in observation group had statistically significant higher scores in theory and skill tests than those in the control group ( P<0.001). The evaluation of boosting their enthusiasm for internship, advancing self-learning ability, conducing to improving learning methods in the future, and enhancing clinical skills and thinking ability in the observation group was significantly better than that in the control group ( P<0.05). Conclusion:The individualized teaching model based on PBL could efficiently alleviate the conflicts between internship and postgraduate entrance examination preparation and improve the effect of gynecology practice teaching.

This corrects the article “Analysis of Tau Protein Expression in Predicting Pathological Complete Response to Neoadjuvant Chemotherapy in Different Molecular Subtypes of Breast Cancer” in volume 23 on page 47.This article was initially published on the Journal of Breast Cancer with a misspelled the abbreviation in figure 3. The abbreviation ‘HP’ should be corrected as ‘HR’.

PURPOSE: Tau is a microtubule-associated protein that can be found in both normal and abnormal breast cells. Whether the expression of Tau protein can predict the response to neoadjuvant chemotherapy (NACT) is still unclear. In this study, we assessed the role of Tau protein expression in predicting a pathological complete response (pCR) to NACT for different subtypes of breast cancer. METHODS: Four hundred and sixty-eight eligible patients were retrospectively recruited in our study. The relationship between clinicopathologic factors, including Tau protein expression, and pCR in different subtypes was evaluated using logistic regression analysis. Correlation between Tau and disease-free survival (DFS) and overall survival (OS) was performed using Kaplan–Meier analysis. RESULTS: The expression of Tau protein was negatively correlated with pCR, especially in triple-negative breast cancer (TNBC). No significant difference was observed in the luminal human epidermal growth factor receptor-2 (HER2)-negative subtype and HER2-positive subtype. Patients with pCR were associated with better DFS and OS (p < 0.05). However, Tau protein expression had no association with either DFS or OS (p > 0.05). CONCLUSION Tau protein expression can predict pCR before NACT in TNBC, but there was no correlation between Tau expression and DFS or OS.

With the continuous development of endovascular surgery, thoracic endovascular aortic repair (TEVAR) has gradually replaced traditional open surgery and has become the preferred treatment strategy for Stanford type B aortic dissection. However, the disadvantage of the short proximal landing zone greatly limited the indication of TEVAR surgery and affected the prognosis. In recent years, many strategies such as hybrid surgery, in vitro fenestrated and branched aortic endo-graft, chimney technique, in-situ fenestration technique, etc., have been developed, which greatly broadens the TEVAR indication and improved the prognosis.

Objective To discuss the effect of low-frequency pulsed electromagnetic field (ELF-PEMFs) combined with-whole-body vibration(WBV) on the bone mineral density,bone microstructure and the biological mechanics performance inhindlimb unloading osteoporosis rats.Methods Forty female 4 months aged SD rats were randomly divided into five groups:blank group,control group,ELF-PEMFs group,WBV group,low-frequency pulsed electromagnetic field combined with wholebody-vibration(ELF-PEMFs + WBV) group.The blank group was the normal control which comprise the healthy rats.The controlgroup was the disused osteoporosis model.Except for the blank group,thehind limb unloading rats were kept for six weeks.No intervention were provided to the blank group and the control group,other three groups were treated with physical therapy.The bodyweight of rats in each group was record.Bone mineral density was measured by Dual energy X-ray absorptiometry.The right femurs was analyzed by Micro-CT and the left femur was tested through a biomechanical machine.Results After 8 weeks of continuous treatment,the ELF-PEMFs group,WBV group,ELF-PEMFs+WBV group were significantly increased in weight and bonedensity (PELF-PEMFs=0.015,PWBV=0.016,PELF-PEMFs+WBV=0.007),(tELF-PEMFs=5.956,PELF-PEMFs=0.000;tWBV=6.127,PWBV=0.000;tELF-PEMFs+WBV=4.639,PELF-PVMFs+WBV=0.000).The difference was statistically significant (F=0.091,P=0.018).The ELF-PEMFs +WBV group was significantly higher in bone formation index.The items of BV/TV,Tb.N,Tb.Th and SMI in Micro-CT analysis increased,while Tb.Sp and Conn.D index decreased significantly.Trabecular bone structure of all the three groups was improved,however the ELF PEMFs +WBV group was better than the other two groups (vs.ELF-PEMF group,PBV/TV=0.041,PTb.N=0.026,PTb.Th=0.009,PConn.D=0.030,PTb.Sp=0.045,PSMI=0.032;VS.WBV group,PBv/Tv=0.018,PTb.N=0.004,PTb.Th=0.022,PConn.D=0.042,PTb.Sp=0.039,PSMI=0.049).The maximum load,energy absorption and bone stiffness index in biomechanicalperformance test were improved.The combination treatment group were significantly improved (F=0.167,P=0.038).Conclusion Low-frequencypulsed electromagnetic field combined with whole body vibration therapy can improve bone mineral density,bone microstructureand the biological mechanics performance.They have synergistic effect and the combination therapy is better than single treatment.