BACKGROUND:Piezo1,a mechanosensitive protein,is tightly connected to osteogenic differentiation,and it has been demonstrated that TAZ has a role in regulating osteogenic differentiation.It is unclear whether TAZ participates in the regulation of osteogenic differentiation of human bone marrow mesenchymal stem cells by Piezo1,so it is crucial to investigate its unique mechanism to prevent osteonecrosis of the femoral head. OBJECTIVE:To elucidate what function Piezo1 plays in osteogenic differentiation and TAZ expression in human bone marrow mesenchymal stem cells. METHODS:The siRNA targeting Piezo1 was constructed and transfected into 293T cells.The silencing efficiency was detected by RT-qPCR.The selected Piezo1-Home-2337 was packaged according to the silencing efficiency,and its optimal multiplicity of infection value was assayed by immunofluorescence staining.The packaged Piezo1 silencing recombinant lentivirus was transfected into human bone marrow mesenchymal stem cells,and its silencing effect was detected by RT-qPCR and western blot assay.Alizarin red staining,alkaline phosphatase activity analysis,immunofluorescence staining,RT-qPCR and western blot assay were utilized to analyze the effect of silencing Piezo1 on the osteogenic differentiation of human bone marrow mesenchymal stem cells. RESULTS AND CONCLUSION:(1)The mRNA and protein levels of Piezo1 in human bone marrow mesenchymal stem cells transfected by si-Piezo1 were decreased significantly,with a statistically significant difference compared with normal and negative control groups.(2)The alkaline phosphatase activity in the si-Piezo1 group was much lower and the calcium deposition in the si-Piezo1 group was significantly reduced compared with the negative control group.(3)The mRNA levels of osteogenesis-related genes including Runt-related transcription factor 2(Runx2),osteopontin(OPN),distal-less homeobox 5(DLX5),osteocalcin,β-catenin and Tafazzin(TAZ)in the si-Piezo1 group were significantly decreased compared with the negative control group.Afterward,the expression levels of TAZ and β-catenin protein in the si-Piezo1 group were down-regulated significantly compared with the negative control group,whereas the expression levels of p-TAZ and p-β-catenin protein in the si-Piezo1 group had the opposite condition.(4)The results of immunofluorescence staining showed that the expression of TAZ and β-catenin in human bone marrow mesenchymal stem cells in the si-Piezo1 group was less compared with the negative control group.(5)These findings indicate that Piezo1 can promote the osteogenic differentiation of human bone marrow mesenchymal stem cells.The osteogenic ability of human bone marrow mesenchymal stem cells is significantly reduced after silencing Piezo1,and the expression of TAZ is also reduced.

Objective To compare the efficacy and safety of vedolizumab(VDZ)and infliximab(IFX)for moderate to severe ulcerative colitis(UC)patients through a multicenter retrospective cohort study.Methods All patients with moderate to severe UC who were naive to biologic agents and treated with IFX or VDZ for at least 14 weeks at 3 hospitals in Southwest China between January 2021 and January 2023 were retrospectively enrolled.The efficacy evaluation indicators,including steroid-free clinical remission rates,clinical remission rates and endoscopic remission rates at weeks 14 and 52 were compared between the 2 groups.The occurrence of adverse events during treatment were recorded.Taking whether mucosal healing could be achieved after 14 and 52 weeks of treatment as the dependent variable,firstly,univariate analysis was performed to analyze the risk factors affecting mucosal healing at weeks 14 and 52,and then multivariate logistic regression analysis was applied to identify the independent risk factors of mucosal healing at the 2 time points.Results A total of 151 patients with moderate to severe UC were included,after propensity score matching(PSM),each group included 57 patients.There were no significant differences in the steroid-free clinical remission rate and clinical remission rate between the 2 groups at weeks 14 and 52(P＞0.05).The endoscopic remission rate at week 14 was significantly higher in the VDZ group than the IFX group[40.4％(23/57)vs 22.8％(13/57),P=0.044],but no such difference was observed at week 52[64.5％(20/31)vs 59.5％(22/37),P=0.669].Multivariate logistic regression analysis showed that left-sided disease(E2)[vs pancolitis(E3)](OR=0.46,95％CI:0.21～0.98,P=0.045)was independent risk factor for mucosal healing at week 14 and a disease duration ≥36 months(OR=0.25,95％CI:0.09～0.66,P=0.005)was independent risk factor for mucosal healing at week 52.No statistical difference was observed in the incidence of adverse events between the 2 groups(1.8％vs 7.0％,P=0.360).Conclusion VDZ and IFX have similar efficacy and safety,and both can be used as first-line options for patients with moderate to severe UC.

Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.

Objective To explore the anti-inflammatory effect of Qingre Jiedu(QRJD)formula on mice with gout and its effect on gut microbiota.Methods Forty C57BL/6 mice weighing 20～22 g were divided into control(CON),model(MOD),allopurinol(ALLO),and QRJD formula(QRJD)groups,and i.g.10 g/0.1 mL carboxymethyl cellulose was administered to the CON every morning from 1 to 35 days.A hyperuricemia mouse model was prepared by intragastric injection of a potassium oxalic acid(500 mg/kg)and yeast extract(10 g/kg)suspension.On day 29,50 μL sterile carboxymethyl cellulose was injected into the right ankle of mice in the CON group under isoflurane-induced anesthesia,and a gouty arthritis model was prepared by injecting the same volume of sodium urate(50 mg/mL)into the right ankle of mice in the other groups.Each group was treated with corresponding drugs every day.On day 35,samples were collected from mice that had been fasted for 6 hours without water.Blood indexes,such as uric acid,creatinine,and urea nitrogen,were assessed.Hematoxylin-eosin and saffranine O-fast green staining was performed on ankle joints.Anti-inflammatory indexes of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)were detected by ankle joints immunohistochemical assay.The cecum contents of mice were collected,and changes in gut microbiota were analyzed by high-throughput sequencing of 16S rDNA.Results(1)After 7 days of treatment,compared with the MOD group,QRJD formula effectively reduced the blood concentrations of uric acid(P＜0.001),creatinine(P＜0.01),and urea nitrogen(P＜0.05),and effectively protected renal functions.(2)Compared with the MOD group,HE staining showed that synovial hyperplasia and inflammatory cell infiltration were reduced in the QRJD formula group after treatment.The cartilage arrangement of the compound was more orderly than before,cartilage destruction was less than that in the MOD group,and no matrix loss was observed.(3)Immunohistochemical analysis of the ankle joint indicated that IL-10 and TGF-β1 were not significantly increased in CON and MOD groups.Compared with the MOD group,IL-10 and TGF-β1 expression in the QRJD formula group were increased(P＜0.05).(4)In terms of biodiversity,the number of MOD-specific OTUs increased by 75 compared to the CON group,while the QRJD was able to reduce the number of MOD-specific OTUs to more closely resemble the CON group;no significant difference was found in α-diversity among the four groups(P＜0.05),whereas β-diversity was more similar to the CON group(P=0.001).(5)Compared with the CON group,the MOD group exhibited increased abundances(P＜0.05)of Ruminococcaceae spp.,Dubosiella sp.,Tyzzerella sp.,Ileibacterium sp.,and Bacteroidales spp..In contrast to the MOD group,the QRJD formula group showed elevated abundances(P＜0.05)of Lactobacillus sp.,Ligilactobacillus sp.,and Bacteroides sp..Furthermore,an interaction network of gut microbiota indicated mutual interactions among these microorganisms.(6)In the correlation analysis between gut microbiota and renal functions as well as anti-inflammatory factors,the relative abundances of Dubosiella sp.,Tyzzerella sp.,and Bacteroidales spp.were significantly positively correlated to SUA and SCR(P＜0.05).However,Lactobacillus sp.,Ligilactobacillus sp.,and Mitochondria spp.exhibited a positive correlation to anti-inflammatory factors IL-10 and TGF-β1 with a more significant association observed for TGF-β1(P＜0.05).(7)COG function prediction suggested that the functions of the QRJD formula group were concentrated on inorganic ion transport and metabolism,and carbohydrate transport and metabolism.Conclusions QRJD effectively modulates immune inflammation and gut microbiota dysbiosis,thereby treating gout.Its mechanism of gout prevention and treatment may involve regulation of gut microbiota diversity and abundance,as well as the control of the abundance of differential bacterial species,such as Ruminococcaceae spp.,Dubosiella sp.,and Lactobacillus sp.,to achieve gout therapy.

This paper interprets the content and recommendations of the guidelines on infection prevention and control in long-term care facilities put forward by the World Health Organization （WHO） during the 2019 coronavirus disease （COVID-19） pandemic， and actively explores the key points of nursing and infection prevention and control measures for the long-term care facilities under the background of repeated outbreaks， with the aim of providing care measures and infection prevention and control measures that suit our national conditions to improve the living standards of the elderly and protect them from viral infection amid the recurring pandemic.

OBJECTIVE: To establish finite element models of different preserved angles of osteonecrosis of the femoral head (ONFH) for the biomechanical analysis, and to provide mechanical evidence for predicting the risk of ONFH collapse with anterior preserved angle (APA) and lateral preserved angle (LPA). METHODS: A healthy adult was selected as the study object, and the CT data of the left femoral head was acquired and imported into Mimics 21.0 software to reconstruct a complete proximal femur model and construct 3 models of necrotic area with equal volume and different morphology, all models were imported into Solidworks 2022 software to construct 21 finite element models of ONFH with LPA of 45°, 50°, 55°, 60°, 65°, 70°, and 75° when APA was 45°, respectively, and 21 finite element models of ONFH with APA of 45°, 50°, 55°, 60°, 65°, 70°, 75° when LPA was 45°, respectively. According to the physiological load condition of the femoral head, the distal femur was completely fixed, and a force with an angle of 25°, downward direction, and a magnitude of 3.5 times the subject's body mass was applied to the weight-bearing area of the femoral head surface. The maximum Von Mises stress of the surface of the femoral head and the necrotic area and the maximum displacement of the weight-bearing area of the femoral head were calculated and observed by Abaqus 2021 software. RESULTS: The finite element models of ONFH were basically consistent with biomechanics of ONFH. Under the same loading condition, there was stress concentration around the necrotic area in the 42 ONFH models with different preserved angles composed of 3 necrotic areas with equal volume and different morphology. When APA was 60°, the maximum Von Mises stress of the surface of the femoral head and the necrotic area and the maximum displacement of the weight-bearing area of the femoral head of the ONFH models with LPA<60° were significantly higher than those of the models with LPA≥60° ( P<0.05); there was no significant difference in each index among the ONFH models with LPA≥60° ( P>0.05). When LPA was 60°, each index of the ONFH models with APA<60° were significantly higher than those of the models with APA≥60° ( P<0.05); there was no significant difference in each index among the ONFH models with APA≥60° ( P>0.05). CONCLUSION From the perspective of biomechanics, when a preserved angle of ONFH is less than its critical value, the stress concentration phenomenon in the femoral head is more pronounced, suggesting that the necrotic femoral head may have a higher risk of collapse in this state.
Adult ; Humans ; Femur Head/surgery* ; Finite Element Analysis ; Stress, Mechanical ; Femur/diagnostic imaging* ; Femur Head Necrosis/surgery*

Objective:To evaluate the efficacy and safety of budesonide viscous suspension (BVS) in preventing extensive esophageal stenosis after endoscopic submucosal dissection(ESD).Methods:Data of 62 cases of early esophageal neoplasms or precancerous lesions receiving ESD whose postoperative mucosal defects were more than half the circumference of the esophageal lumen at Fujian Provincial Hospital from October 2014 to December 2018 were retrospectively studied. The patients were divided into the BVS group who received BVS therapy (n=24) and the control group who received no intervention (n=38). The incidence of postoperative stenosis, the number of bougie dilation procedures and complications were compared between the two groups. Risk factors for postoperative stricture were analyzed by logistic regression.Results:The incidence of postoperative stenosis [16.7% (4/24) VS 47.3% (18/38), P=0.005], the number of bougie dilation procedures (1.50±0.58 VS 2.70±1.09, P=0.039) in the BVS group were significantly lower than those in the control group. No serious adverse events such as perforation or massive hemorrhage related to BVS were observed in the BVS group. Multivariate logistic regression analysis showed circumferential extension ≥3/4 ( OR=37.970, 95% CI: 6.338-227.482) and non-intervention with BVS( OR=20.962, 95% CI: 3.374-130.243) were the independent risk factors for esophageal stricture after ESD. Conclusion:Administration of BVS is an effective and safe method to reduce the incidence of stenosis and the number of bougie dilation procedures for extensive esophageal stenosis after ESD.

Background and Objectives: Mesenchymal stromal cells (MSCs)-based treatment for degeneration of intervertebral disc (IVD) has been proposed recently. We here addressed whether MSC secreted factors can rejuvenate nucleus pulposus- derived stem/progenitor cells from degenerated disc (D-NPSCs) in vitro. Methods: and Results: We analyzed the expression of MSCs and NP cell specific surface markers, pluripotency related genes, multilineage potential and cell proliferative capacity of D-NPSCs upon incubation with the conditioned medium which was collected from the umbilical cord derived MSCs (UCMSCs). Our results indicated that the conditioned medium restore the stemness of D-NPSCs by up-regulating the expression level of CD29 and CD105, pluripotency related genes OCT4 and Nanog, and NP progenitor marker Tie2. The increased stemness was accompanied by promoted cell proliferative capacity and improved osteogenic and chondrogenic differentiation potential. Conclusions Our findings suggested that the UCMSCs derived conditioned medium might be used to rejuvenate the degenerated NP stem/progenitor cells.

OBJECTIVETo systematically assess the safety and efficacy of hand-assisted laparoscopic distal gastrectomy (HALG) versus open distal gastrectomy (ODG) for gastric cancer.

METHODSChinese or English literature regarding comparison of HALG and ODG were collected by searching in databases (such as PubMed, Cochrane Library, CNKI, Wanfang database) between January 1996 and September 2016. The data of operative time, incision length, blood loss, number of harvested lymph nodes, time to flatus, hospital stay, postoperative complication morbidity and long-term outcomes were compared between the two procedures. Then funnel plot was used to evaluate publication bias and sensitivity analysis was used to evaluate the stability of the results. All these data analyses were performed using the Meta for or Meta package of R version 3.3.1.

RESULTSA total of 7 studies with 835 patients (323 cases in HALG group and 512 cases in ODG group) were included. Compared with ODG, HALG had a longer operative time (WMD=28.93 minutes, 95%CI=9.59 to 48.28, Z=2.93, P=0.000), a shorter incision length (WMD=-10.31 cm, 95%CI=-14.01 to -6.62, Z=-5.47, P=0.000), less blood loss (WMD=-140.08 ml, 95%CI=-215.07 to -65.09, Z=-3.66, P=0.000), faster gastrointestinal recovery (WMD=-1.23 days, 95%CI=-1.89 to -0.56, Z=-3.62, P=0.000), shorter postoperative hospital stay (WMD=-3.24 days, 95%CI=-5.47 to -1.02, Z=-2.85, P=0.000). In subgroup analysis, 3 studies published before 2013 vs. 4 studies published afterwards, the number of harvested lymph nodes (WMD=-0.78, 95%CI=-2.05 to 0.50, Z=-1.19, P=0.235) and postoperative complication morbidity (RR=1.02, 95%CI=0.43 to 2.44, Z=0.05, P=0.961) did not differ significantly between two groups. Compared with ODG, the RR(95%CI) of ileus of HALG was 0.43 (0.07 to 2.82), but the difference was not statistically significant (P=0.383). One study reported the 5-year overall survival rates of HALG and ODG were 81.0% vs 67.5%, and the tumor recurrence rates were 7.1% vs 22%, respectively, but the differences were not statistically significant(all P>0.05). Sensitivity analysis showed that the above results were stable. The funnel plots of the lymph nodes and postoperative complication morbidity did not present significant publication bias.

CONCLUSIONSHALG has the advantages of minimal invasiveness such as shorter incision length and quicker recovery. Furthermore, the short-term efficacy of HALG is similar to conventional open surgery. However, the long-term efficacy is lack of support from multicenter long-term follow-up results.

Blood Loss, Surgical ; statistics & numerical data ; Comparative Effectiveness Research ; Gastrectomy ; methods ; Hand-Assisted Laparoscopy ; adverse effects ; Humans ; Length of Stay ; statistics & numerical data ; Lymph Node Excision ; statistics & numerical data ; Neoplasm Recurrence, Local ; epidemiology ; Operative Time ; Postoperative Complications ; epidemiology ; Postoperative Period ; Recovery of Function ; Stomach Neoplasms ; mortality ; surgery ; Survival Rate ; Time ; Treatment Outcome

Objective To explore the the effect of psychological intervention on emotion and postoperative bladder spasm in elderly patients with benign prostatic hyperplasia. Methods 40 elderly cases with benign prostatic hyperplasia were classified as the control group and were given the routine intervention, the other 40 cases were received psychological intervention at the basis of routine intervention and classified as the observation group. The two groups were treated in Anji county traditional Chinese medicine hospital from September 2015 to January 2017. Results The anxiety and depression in the 2 groups had no significant difference before intervention, and the prognosis in the observation group was better than that in the observation group after intervention. The bladder spasm in the two groups was compared. The third days after the operation, the incidence of bladder spasm in the observation group was 10.0%, which was significantly lower than 45.0% in the control group, and the difference between the 2 groups was statistically significant (P<0.05). Conclusion Psychological intervention has better effect on mood and bladder spasm in elderly patients with prostate hyperplasia. It can help patients to improve their emotional state, reduce anxiety and depression, and ultimately reduce the incidence of bladder spasm, which is worthy of clinical reference.