Objective To investigate the effect of miR-129-1-3p on the osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)and its potential mechanism.Methods Negative control group,the miR-129-1-3p mimic group,the miR-129-1-3p inhibitor group and the corresponding negative control were constructed and transfected into hBMSCs.The formation of calcium-mineralized nodules was observed by alkaline phosphatase staining and alizarin red S staining.The expression levels of miR-129-1-3p and osteogenic differentiation markers were detected by qRT-PCR.Western blot detected the protein expressions of bone mor-phogenetic protein 2(BMP2),SMAD1 and p-SMAD1.Results After transfection,the expression level of miR-129-1-3p in mimic group was significantly increased(P＜0.05),the number of mineralized nodules was significantly decreased,and the expression levels ofBMP2,Runt-related transcription factor 2(RUNX2),osteocalcin(OCN)mRNA were significantly down-regulated(P＜0.05).BMP2 and p-SMAD1 protein were also significantly down-regulated(P＜0.05)compared with Mimic-NC group.The expression levels of BMP2,RUNX2,OCN mRNA were significantly up-regulated in inhibitor group(P＜0.05)compared with Inhibitor-NC group.BMP2 and p-SMAD1 protein were significantly up-regulated in inhibitor group(P＜0.05).Conclusion miR-129-1-3p can inhibit the osteo-genic differentiation of human bone marrow mesenchymal stem cells by suppressing BMP2/SMAD1 signaling pathway.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Aim To investigate the effects of SAHA on the expression of P-gp and the pharmacokinetic pa-rameters of its substrate phenytoin sodium in rats under hypoxic environments.Methods Wistar rats were randomly divided into the normioxic group,the hypoxic model group,and the low-,medium-and high-dose vorinostat(SAHA)groups.Liver tissues were col-lected,and the expression levels of P-gp and HDAC5 were detected by Real-time PCR and Western blot.The morphological changes of liver tissues were ob-served by HE staining.Following intragastric adminis-tration of 50 mg·kg-1 phenytoin sodium to each group,blood samples were collected,and the plasma concentration of phenytoin sodium was determined u-sing UFLC-MS/MS to calculate pharmacokinetic pa-rameters.Results Compared with the normoxic group,the expression of HDAC5 in the liver tissues of hypoxia model rats increased,while the expression of P-gp decreased.After SAHA treatment,HDAC5 expression decreased,and P-gp expression increased.Among the SAHA groups,the medium-dose group showed the most significant effect,and HE staining re-sults indicated that this concentration did not cause damage to rat liver tissues.Compared with the normox-ic group,the AUC,Cmax,and T1/2 of phenytoin sodium in hypoxia model rats were significantly raised.After administration of the medium dose of SAHA,the AUC,Cmax,MRT,and T1/2 were significantly reduced,while CLZ/r was significantly increased.Conclusions Un-der hypoxic environments,the expression of P-gp in rat liver tissue is significantly downregulated,leading to increased systemic exposure of phenytoin,reduced clearance,and consequently elevated blood concentra-tions,raising the risk of central nervous system toxici-ty.In contrast,SAHA suppresses HDAC5 expression,thereby activating P-gp transcription and enhancing its efflux function.This results in decreased systemic ex-posure and improved clearance of phenytoin,signifi-cantly reducing drug accumulation in body and ulti-mately lowering the risk of adverse effects.

Aim To explore the effect of FTO on adria-mycin resistance in triple-negative breast cancer through the Wnt/β-catenin signaling pathway and to reveal the underlying mechanism.Methods The MDA-MB-231/ADR drug-resistant cell line was constructed using a method of gradually increasing adriamycin concentra-tion with intermittent induction.The half-inhibitory concentration(IC50)of adriamycin for MDA-MB-231 and MDA-MB-231/ADR cells and the expression of FTO were compared.After knocking down FTO in MDA-MB-231/ADR cells,CCK-8,qRT-PCR,colony formation assay,transwell,flow cytometry,and Western blot were used to assess the changes in the IC50 of adri-amycin,cell proliferation,migration,invasion,apopto-sis,and the expression of related proteins.Results FTO was highly expressed in MDA-MB-231/ADR cells.After FTO knockdown,the IC50 value of adriamy-cin in MDA-MB-231/ADR cells decreased,and the a-bilities of proliferation,migration and invasion were weakened.In the FTO knockdown group,the expres-sion levels of Bax,cleaved-caspase3,GSK-3 β proteins and the apoptosis rate significantly increased,while the expression levels of Bcl-2,Wnt5a,β-catenin,c-myc,cyclin D1,and P-gp proteins decreased.Conclusion FTO may inhibit the apoptosis of MDA-MB-231/ADR cells through the Wnt/β-catenin signaling pathway,al-ter P-gp expression,and thereby enhance the resistance of MDA-MB-231/ADR cells to adriamycin.

Objective To analyze the efficacy of autologous tissue repair for rectocele through the perineal approach in treating constipation and fecal incontinence in patients.Methods From January 2021 to November 2022,23 female patients with symptomatic rectal protrusion were treated with perineal autologous tissue repair.Preoperatively and at 12 months postoperatively,the Cleveland Clinic Constipation Score(CCCS),Cleveland Clinic Incontinence Score(CCIS),and Patient Assessment of Constipation Quality of Life(PAC-QOL)questionnaires were used to assess postoperative outcomes and quality of life.Results Among the 23 patients,with a median follow-up time of 12.6 months,CCCS decreased from 17.09±1.68 to 3.96±2.08(P＜0.05);CCIS decreased from 1.52±4.15 to 0.52±1.41(P＞0.05);PAC-QOL:physical discomfort decreased from 13.00±1.51 to 4.74±1.98;psychological discomfort decreased from 20.96±3.27 to 5.74±2.67;concern and anxiety decreased from 26.13±4.37 to 8.78±3.14;satisfaction decreased from 15.39±2.35 to 4.60±1.59(P＜0.05).All patients showed significant improvement in constipation and incontinence symptoms postoperatively,with no serious postoperative complications and a marked improvement in postoperative quality of life.Conclusion Rectocele repair with perineal approach using autologous tissue is an effective and safe method,avoiding potential potential complications associated with grafts.

With the continuous evolution of minimally invasive surgical concepts,operative techniques are progressively advancing from"minimal injury"toward"scarless"approaches.Super-minimally laparoscopic surgery(SMLS)is a novel surgical modality developed on the basis of conventional laparoscopic techniques through the innovation and recombination of operative elements,aiming to achieve smaller trauma and improved cosmetic outcomes.Utilizing the umbilical skin fold as a natural scar-concealing site,SMLS establishes no more than two primary operating channels(maximum diameter≤15 mm),supplemented by auxiliary ports≤2 mm in diameter on the abdominal wall.Combined with innovative separable surgical instruments and high-definition visualization systems,this approach provides a systematic solution to key issues such as residual access-site scarring.This review summarizes the development,technical innovations,current clinical applications,and potential aesthetic value of SMLS in the evolution of minimally invasive surgery,aiming to offer theoretical insights and research reference for its future promotion and technical refinement.

Objective:To investigate the prognostic effect of femoral resection on patients with soft tissue sarcoma of the thigh with cortical bone involvement.Methods:This retrospective study included patients with soft tissue sarcoma of the thigh diagnosed and treated in the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to December 2021. Patients were divided into two groups based on whether femoral resection and reconstruction were performed with 20 in the resection group and 86 in the non-resection group. Propensity score matching (PSM) was used to control confounding variables. Overall Survival, recurrence free survival, metastasis free survival, and postoperative functional outcomes were compared between groups before and after PSM. Cox proportional hazards regression was used to identify risk factors for death, recurrence, and metastasis.Results:Before PSM, the 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 46.7% and 36.7% in the resection group, compared to 69.7% and 60.3% in the non-resection group without significant differences ( P>0.05). However, the 5-year metastasis-free survival (MFS) rate was significantly lower in the resection group (40.0%) compared to the non-resection group (73.1%) ( P=0.021). After PSM, the 5-year OS, RFS, and MFS in the resection group were 46.7%, 36.7%, and 35.9%, respectively, compared to 45.0%, 39.4%, and 67.7% in the non-resection group, with no significant differences ( P>0.05). The median postoperative MSTS functional score after PSM was significantly lower in the resection group 23(18, 25) points than in the non-resection group 26.5(24.3, 27.8) points ( U=43.000, P=0.007). Multivariate Cox regression analysis identified grade III histology ( HR=3.794, P=0.002) and tumor involvement angle around the femur greater than 180° ( HR=2.729, P=0.030) as independent risk factors for death. Age over 55 years ( HR=4.185, P=0.015), tumor diameter greater than 8 cm ( HR=4.290, P=0.014), and involvement of the intermuscular compartment ( HR=3.794, P=0.017) were associated with increased risk of local recurrence. Grade III histology ( HR=3.848, P=0.006) and involvement of the intermuscular compartment ( HR=2.500, P=0.045) were associated with distant metastasis. Conclusion:For patients with thigh soft tissue sarcoma involving femoral cortex involvement but no medullary cavity invasion, bone resection did not improve survival, recurrence or metastasis compared with patients in non-resection group. A relatively more conservative surgical approach may be advisable to preserve limb function without compromising oncological prognosis.

Objective:To construct a nursing norm for extracorporeal membrane oxygenation in adults, so as to provide a reference for improving the nursing care of adult extracorporeal membrane oxygenation.Methods:The first draft was developed through literature search and expert discussion. From September to October 2023, 16 experts were selected using the Delphi method to conduct two rounds of expert consultation on the first draft, and the final draft was revised with reference to the experts' comments. The expert positivity coefficient was expressed as the effective recovery rate of the questionnaire, and the degree of expert authority was evaluated with the authority coefficient, and the degree of harmonization of expert opinions was assessed with the Kendall's harmony coefficient.Results:Literature search screened a total of four guidelines and five expert consensus. In the two rounds of consultation, the effective recovery rates of the questionnaires were all 100% (16/16), and the expert authority coefficients were all 0.900, and the Kendall's harmony coefficients of the overall indicators were 0.581 and 0.666, respectively (both P<0.01). The final constructed nursing norm for extracorporeal membrane oxygenation in adults included five primary indicators, 27 secondary indicators, and 17 tertiary indicators. Conclusions:The constructed nursing norm for extracorporeal membrane oxygenation in adults is scientific, reliable and feasible, and can guide clinical nursing staff to carry out nursing care for extracorporeal membrane oxygenation.

Aim To investigate the effects of SAHA on the expression of P-gp and the pharmacokinetic pa-rameters of its substrate phenytoin sodium in rats under hypoxic environments.Methods Wistar rats were randomly divided into the normioxic group,the hypoxic model group,and the low-,medium-and high-dose vorinostat(SAHA)groups.Liver tissues were col-lected,and the expression levels of P-gp and HDAC5 were detected by Real-time PCR and Western blot.The morphological changes of liver tissues were ob-served by HE staining.Following intragastric adminis-tration of 50 mg·kg-1 phenytoin sodium to each group,blood samples were collected,and the plasma concentration of phenytoin sodium was determined u-sing UFLC-MS/MS to calculate pharmacokinetic pa-rameters.Results Compared with the normoxic group,the expression of HDAC5 in the liver tissues of hypoxia model rats increased,while the expression of P-gp decreased.After SAHA treatment,HDAC5 expression decreased,and P-gp expression increased.Among the SAHA groups,the medium-dose group showed the most significant effect,and HE staining re-sults indicated that this concentration did not cause damage to rat liver tissues.Compared with the normox-ic group,the AUC,Cmax,and T1/2 of phenytoin sodium in hypoxia model rats were significantly raised.After administration of the medium dose of SAHA,the AUC,Cmax,MRT,and T1/2 were significantly reduced,while CLZ/r was significantly increased.Conclusions Un-der hypoxic environments,the expression of P-gp in rat liver tissue is significantly downregulated,leading to increased systemic exposure of phenytoin,reduced clearance,and consequently elevated blood concentra-tions,raising the risk of central nervous system toxici-ty.In contrast,SAHA suppresses HDAC5 expression,thereby activating P-gp transcription and enhancing its efflux function.This results in decreased systemic ex-posure and improved clearance of phenytoin,signifi-cantly reducing drug accumulation in body and ulti-mately lowering the risk of adverse effects.

Aim To explore the effect of FTO on adria-mycin resistance in triple-negative breast cancer through the Wnt/β-catenin signaling pathway and to reveal the underlying mechanism.Methods The MDA-MB-231/ADR drug-resistant cell line was constructed using a method of gradually increasing adriamycin concentra-tion with intermittent induction.The half-inhibitory concentration(IC50)of adriamycin for MDA-MB-231 and MDA-MB-231/ADR cells and the expression of FTO were compared.After knocking down FTO in MDA-MB-231/ADR cells,CCK-8,qRT-PCR,colony formation assay,transwell,flow cytometry,and Western blot were used to assess the changes in the IC50 of adri-amycin,cell proliferation,migration,invasion,apopto-sis,and the expression of related proteins.Results FTO was highly expressed in MDA-MB-231/ADR cells.After FTO knockdown,the IC50 value of adriamy-cin in MDA-MB-231/ADR cells decreased,and the a-bilities of proliferation,migration and invasion were weakened.In the FTO knockdown group,the expres-sion levels of Bax,cleaved-caspase3,GSK-3 β proteins and the apoptosis rate significantly increased,while the expression levels of Bcl-2,Wnt5a,β-catenin,c-myc,cyclin D1,and P-gp proteins decreased.Conclusion FTO may inhibit the apoptosis of MDA-MB-231/ADR cells through the Wnt/β-catenin signaling pathway,al-ter P-gp expression,and thereby enhance the resistance of MDA-MB-231/ADR cells to adriamycin.