Objective:To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant(hUCMSCs-Sup)on the proliferation,apoptosis,and endometrium receptivity of the human endometrial stromal cells(hEndoSCs)treated with mifepristone(Ms),and to clarify the possible mechanism.Methods:The hEndoSCs were cultured in vitro and divided into control group and 40,60,80,and 100 μmol·L-1 Ms groups.The survival rates of the cells in various groups were detected by MTT assay.The hEndoSCs were divided into control group,40 μmol·L-1 Ms group,and 60 μmol·L-1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of apoptosis-related protein B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method,and the ratio of Bcl-2/Bax was calculated.After treated with hUCMSCs-Sup,the hEndoSCs were divided into control group,Ms group,Ms+hUCMSCs-Sup group,and Ms+hUCMSCs-Sup+3-methyladenine(3-MA)group.The survival rates of the cells in various groups were detected by MTT assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)and microtubule-associated protein 1 light chain 3B-I(LC3B-Ⅰ)proteins in the cells in various groups were detected by Western blotting method,and the ratio of LC3B-Ⅱ/LC3B-Ⅰwas calculated;the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with control group,the survival rates of the cells in 40,60,80,and 100 μmol·L-1 Ms groups were significantly decreased(P<0.05)in a time-dependent and dose-dependent manner.Compared with control group,the apoptotic rates of the cells in 40 and 60 μmol·L-1 Ms groups were significantly increased(P<0.05),and the ratios of Bcl-2/Bax were significantly decreased(P<0.05).After treated with hUCMSCs-Sup,compared with control group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased(P<0.05),the apoptotic rate was significantly increased(P<0.05),and the expression levels of homeobox A10(HOXA10),leukemia inhibitory factor(LIF),and integrin subunit beta 3(ITGB3)mRNA in the cells were significantly decreased(P<0.05);compared with Ms group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰin the cells in Ms+hUCMSCs-Sup group were significantly increased(P<0.05),the apoptotic rate was significantly decreased(P<0.05),and the expression levels of HOXA10,LIF,and ITGB3 mRNA in the cells were significantly increased(P<0.05);compared with Ms+hUCMSCs-Sup group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased(P<0.05).Conclusion:hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms,and increase the endometrium receptivity,and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.

Objective To investigate the effects of force on mechanical stability of FLNa-Ig21/αⅡbβ3-CT complex and the regulation mechanism.Methods The FLNa-Ig21/αⅡbβ3-CT crystal structures were taken from the PDB database.The stability of the complexes in a physiological environment as well as the unfolding path and mechanical stability induced by mechanical forces were analyzed using equilibrium and steered molecular dynamics simulations.Results During the equilibration,the survival rate of most salt bridge and hydrogen bonds was below 0.5,and the interactions between FLNa-Ig21 and αⅡbβ3-CT was relatively weak.During stretching at a constant velocity,the complex could withstand a tensile force of 70-380 pN,and its mechanical strength depended on the force-induced dissociation path.Under a constant force of 0-60 pN,the complexes exhibited a slipping-bond trend,and the force increase facilitated the breakage of the R995-D723 salt bridge and the activation of αⅡbβ3 integrin.Conclusions The force-induced allostery of αⅡbβ3-MP enhanced the complex mechanical strength and delayed FLNa-Ig21 dissociation from αⅡbβ3-CT.After breaking through the 20 pN threshold,force positively regulated the activation of αⅡbβ3 integrin.These results provide insights into the molecular mechanism of αⅡbβ3 activation and the development of related targeted drugs.

OBJECTIVE To systematically evaluate the real-world effectiveness and safety of belimumab in the treatment of lupus nephritis （LN） in Chinese adult patients. METHODS Retrieved from PubMed， Embase， Web of Science， Cochrane Library， Wanfang data， CNKI， VIP and CBM， real-world studies on belimumab in the treatment of LN in Chinese adult patients were collected from the inception to July 7th， 2023. Two reviewers independently screened the literature， extracted data， and assessed the quality of the included studies. Meta-analysis was then performed using RevMan 5.3 software. RESULTS A total of 10 real- world studies were included， involving 253 Chinese adult patients with LN. The results of the meta-analysis demonstrated that the complete renal response rate， partial renal response rate， and the incidence of adverse reaction rate in Chinese adult patients with LN treated with belimumab were 61% （95%CI was 46%-76%， P＜0.000 01）， 23%（95%CI was 2%-44%， P＝0.03）， and 30% （95%CI was 16%-43%， P＜0.000 01）， respectively. Belimumab could reduce the 24-hour urinary protein （MD＝－1.71， 95%CI was －3.02-－0.40， P＝0.01）， urine protein-creatinine ratio （MD＝－1.76，95%CI was －2.06-－1.46，P＜0.000 01）， the systemic lupus erythematosus disease activity index （MD＝－8.63， 95%CI was －12.12-－5.13， P＜0.000 01）， and glucocorticoids dosage （MD＝－18.65， 95%CI was －31.82-－5.48， P＝0.006）. In addition， it could elevate the levels of complement C3 （MD＝0.19， 95%CI was 0.08-0.30， P＝0.000 6） and complement C4 （MD＝0.06， 95%CI was 0.02-0.09， P＝0.001）. However， belimumab could not improve the levels of serum creatinine and estimated glomerular filtration rate （P＞0.05）. CONCLUSIONS Belimumab has good efficacy and safety in Chinese adult patients with LN.

Objective:To discuss the effect of Wnt/β-catenin signaling pathway inhibitor methyl 3-｛[(4-methyl-phenyl)sulfonyl]amino ｝ benzoate(MS AB)on the fibrogenic response of the human endometrial stromal cells(HESCs),and to provide the foundation for the application of MSAB in the target therapy of intrauteriue adhesion(JUA).Methods:The normal HESCs were cultured in vitro and divided into two groups:control group and transforming growth factor β1(TGF-β1)group;the HESCs from the adhesion part of the IUA patients were cultured in vitro,regarded as IUA group.Western blotting method was used to detect the expression levels of fibrotic marker protein type Ⅰ collagen α1(COL1A1)in the cells in various groups at different time points(0,12,24,48,and 60 h)after treated with TGF-β1.MTT assay was used to detect the proliferation activities of the cells in various groups.Western blotting method was used to detect the expression levels of the fibrotic marker protein COL1A1,stromal marker proteins such as N-cadherin and α-smooth muscle actin(α-SMA),and Wnt/β-catenin signaling pathway-related protein β-catenin in the cells in control and IUA groups.Based on the MSAB concentrations,the normal HESCs were divided into 0(control),0.25,0.50,0.75,and 1.00 μmol·L-1 MSAB groups,and MTT assay was used to detect the survival rates of the cells in various groups.After treated with MSAB,the normal HESCs were divided into control group(normal HESCs),TGF-β1 group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with complete culture medium,and the cells continued to be cultured for 24 h),and MSAB group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with a complete medium containing 0.75 μmol·L-1 MSAB and the cells continued to be cultured for 24 h).Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of epithelial-mesenchymal transition(EMT)-related transcription factors Snail,Slug,Smuc,ZEB1,and ZEB2,and COL1A1 mRNA in the cells in various groups.Western blotting method was used to detect the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in various groups.Results:Compared with control group(after treated with TGF-β1 for 0 h),the expression levels of COL1A1 proteins in the HESCs after treated with TGF-β1 for 12,24,48,and 60 h in TGF-β1 group were increased(P＜0.05 or P＜0.01).Compared with control group,there was no significant difference in the proliferation activity of the HESCs in IUA and TGF-β1 groups(P＞0.05).Compared with control group,the expression levels of COL1A1,β-catenin,N-cadherin,and α-SMA proteins in the cells in IUA group were increased(P＜0.05 or P＜0.01).Compared with control group,the survival rates of the cells in 0.75 and 1.00 μmol·L-1 MSAB groups were decreased(P＜0.05 or P＜0.01).Compared with control group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in TGF-β1 group were increased(P＜0.05 or P＜0.01);compared with TGF-β1 group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in MSAB group were decreased(P＜0.05 or P＜0.01).Compared with control group,after treated with TGF-β1 for 24 h,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in TGF-β1 group were increased(P＜0.01);compared with TGF-β1 group,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in MSAB group were decreased(P＜0.05 or P＜0.01).Conclusion:MSAB can inhibit the fibrogenic responses of the HESCs in vitro,and the results provide the theoretical basis for the application of MSAB in the target therapy of IUA.

Objective:To investigate the effects of bisphenol A(BPA)on the proliferation activity and stemness characteristics of endometrial mesenchymal stem/stromal cells(eMSCs),and to elucidate the improvement effect of human umbilical cord mesenchymal stem cell-derived supernatant(hUCMSC-Sup)on the cell injury.Methods:The eMSCs were cultured in vitro and treated with different concentrations of BPA(0,200,250,300,350,and 400 μmol·L-1).The eMSCs were divided into control group(only cultured with culture solution),BPA group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA),BPA+hUCMSC-Sup group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 50%volumetric ratio of hUCMSC-Sup),and BPA+CHIR-99021 group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 10 μmol·L-1 CHIR-99021).The survival rates of eMSCs in various groups were detected by methyl thiazolyl tetrazolium(MTT)assay.The numbers and diameters of the spheroids in various groups were detected by spheroids formation assay,the proliferation activities of the cells in eMSCs stem cell spheroids in various groups were detected by CCK-8 assay;the percentage of CD73+cells in eMSCs in various groups were detected by flow cytometry;the expression levels of sex determining region Y-box 2(Sox2),octamer-binding transcription factor 4(Oct4),and Nanog mRNA in the eMSCs in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method,the expression levels of β-catenin protein in the eMSCs in various groups were detected by Western blotting method.Results:The MTT results showed that after treated with BPA for 24 and 48 h,compared with 0 μmol·L-1 BPA group,the survival rates of eMSCs in 200,250,300,350,and 400 μmol·L-1 BPA groups were significantly decreased(P<0.01).At 24 and 48 h after treatment,compared with control group,the survival rate of the eMSCs in BPA group was significantly decreased(P<0.01);at 48 h after treatment,compared with BPA group,the survival rate of the eMSCs in BPA+hUCMSC-Sup group was significantly inereased(P<0.05).The spheroids formation assay results showed that compared with culture 3 d group,the numbers and diameters of stem cell spheroids of the eMSCs in culture 4 d group and culture 5 d group were significantly increased(P<0.05 or P<0.01);compared with control group,after 48 h of culture,the number and diameter of the cells in eMSCs stem cell spheroids in BPA group were significantly decreased(P<0.05 or P<0.01).The CCK-8 results showed that after 24 and 48 h of treatment,compared with control group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA group was significantly decreased(P<0.01);compared with BPA group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The flow cytometry results showed that compared with control group,the percentage of the CD73+cells in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the percentage of the CD73+cells in eMSCs in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The RT-qPCR results showed that compared with control group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA group were significantly decreased(P<0.01);compared with BPA group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression level of β-catenin protein in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the expression levels of β-catenin protein in the eMSCs in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were signifrcantly inereased(P<0.01).Conclusion:BPA can inhibit the stemness characteristics of the eMSCs,and injury the self-renewal and repair of endometrium;its mechanism may be related to down-regulating the activity of Wnt/β-catenin signal pathway in the cells.hUCMSC-Sup can promote the proliferation of injured eMSCs,and has improvement effect on the stemness injury induced by BPA.

Objective:To investigate damaging effects of clomifene citrate(CC)on endometrial stromal cells(hEndoSCs),and to study effects of spermidine on autophagy and inflammatory cytokine expression in damaged endometrial stromal cells.Methods:Groups were firstly divided into control group,spermidine group,clomiphene group(CC group),CC+Spermidine group.MTT assay was used to detect cell survival rate of hEndoSCs after co-incubation with different concentrations of CC or Spermidine for 24 h.Con-tent of intracellular reactive oxygen species(ROS)and level of apoptosis in cells of the 4 groups were detected by flow cytometry tech-nique.Western blot was used to detect expressions of autophagy pathway-related proteins ULK1,p-ULK1,LC-3Ⅱ,and apoptosis-re-lated proteins Bax,Bcl-2,Cleaved-caspase 3.RT-qPCR was used to detect mRNA expressions of IL-6,IL-1β and TNF-α.Results:Compared with control group,CC group showed decreased cell survival,increased apoptosis rate,ROS content,Bax,Cleaved-cas-pase 3 expressions,decreased Bcl-2 expression,decreased levels of autophagy-related proteins p-ULK1 and LC-3Ⅱ/Ⅰ,and elevated expressions of inflammatory factors IL-6,IL-1β and TNF-α mRNA(P<0.01).There was no significant changes viability of cells in spermidine group compared with control group(P>0.05).Compared with CC group,cell survival rate in CC+spermidine group was sig-nificantly increased,apoptosis rate,ROS content,Bax and Cleaved-caspase 3 expressions were decreased,Bcl-2 expression was in-creased,expressions of autophagy-related proteins p-ULK1 and LC-3Ⅱ/Ⅰ were elevated,while expressions of inflammatory factors IL-6,IL-1β and TNF-α mRNA were decreased(P<0.01).Conclusion:CC can inhibit endometrial stromal cell proliferation,promote apoptosis,and increase the transcript levels of inflammatory factors IL-6,IL-1β and TNF-α.Spermidine can reduce intracellular ROS in clomiphene-injured endometrial stromal cells by activating cellular autophagy,increase cell survival,and inhibit the expressions of inflammatory factors IL-6,IL-1β and TNF-α.

Clinical practice is an integral part of training ICU specialist nurses and an essential stage of training specialist nursing personnel. It is crucial to establish qualified clinical training bases and implement scientific management to ensure the quality of training for specialist nurses. This article elaborates on the current development status and problems of constructing training bases for ICU specialist nurses in China. It provides prospects for future base construction to provide a reference for the sustainable development of training bases for ICU specialist nurses in China.

Objective:To explore the current situation of homogenized operational skills training for Chinese intensive care specialist nurses nationwide.Methods:In July 2023, convenience sampling was used to select 80 teachers who participated in the First Intensive Care Specialist Nurse Teacher Training Course of the Chinese Nursing Association as participants. The survey was conducted using the Chinese Intensive Care Specialist Nurse Teacher Homogenized Operational Skills Assessment Questionnaire, which included adult cardiopulmonary resuscitation, defibrillation, arterial blood gas specimen collection, and mechanical ventilation airway suction.Results:A total of 80 questionnaires were distributed, and 80 valid questionnaires were collected, with a valid response rate of 100.0%. The results showed that the pass rate of adult cardiopulmonary resuscitation assessment for female teachers was higher than that for male teachers, and the pass rate for teachers aged 40 and above was higher than that of other age groups. The pass rate of teachers who obtained the qualification of intensive care specialist nurses from the Chinese Nursing Association was relatively high. The above differences were statistically significant ( P<0.05). In the assessment of operational skills, there were 81 problems with adult cardiopulmonary resuscitation, 51 problems with defibrillation, 39 problems with arterial blood gas specimen collection, and 37 problems with mechanical ventilation airway suction. Conclusions:The overall operational skills assessment of the teacher in the First Intensive Care Specialist Nurse Teacher Training Course of the Chinese Nursing Association is good. However, males under 40 years old and teachers qualified as intensive care specialist nurses by nursing associations in various provinces and cities need to improve their operational skills further.

Objective To investigate the expression of myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), IL-17-producing CD4 + T cells (Th17), and CD8 + T cells (Tc17) in hepatitis B virus-related acute-on-chronic pre-liver failure (pre-ACHBLF), and to provide ideas for the early treatment of acute-on-chronic hepatitis B liver failure (ACHBLF). Methods A total of patients with pre-ACHBLF and 15 patients with ACHBLF who were hospitalized in Shijiazhuang Fifth Hospital, from August 2018 to May 2019 were enrolled as subjects, and 15 patients with chronic hepatitis B (CHB) and 15 healthy controls (HC) who underwent physical examination were enrolled as controls. Flow cytometry was used to measure the expression levels of MDSC and Th17, Treg, and Tc17 cells in peripheral blood; a blood analyzer was used to measure routine blood parameters and calculate neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index(SIRS) to evaluate the degree of inflammation, and the correlation between the expression of immune cells and the degree of inflammation was analyzed. An analysis of variance for independent samples was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Nemenyi test was used for further comparison between two groups. A Pearson linear correlation analysis or Spearman's rank correlation analysis was used to investigate the correlation between variables. Results Compared with the CHB group, the ACHBLF and pre-ACHBLF groups had significant increases in the expression levels of Th17, Treg, and Tc17 cells, and the pre-ACHBLF group also had a significant increase in the expression level of MDSC (all P < 0.05). The correlation analysis showed that in pre-ACHBLF patients, MDSC were positively correlated with leukocyte count, neutrophil count, NLR, MLR, and SII ( r =0.775, 0.727, 0.571, 0.786, and 0.846, all P < 0.05), and Treg cells were only positively correlated with leukocyte count ( r =0.618, P =0.043); Th17/Treg ratio and Tc17 cells were negatively correlated with the number of lymphocytes ( r =-0.790 and -0.795, both P < 0.05). Conclusion Cellular immune dysfunction is observed in patients with pre-ACHBLF, and the expression of MDSC is closely associated with the degree of inflammation and should be taken seriously in the early stage.

Pediatric idiopathic nephrotic syndrome (INS) is characterized by massive albuminuria, hypoproteinemia, edema and hyperlipidemia, with a long course and high probability of relapse and prolongation. Long-term complications caused by long-term usage of hormones and immunosuppressants in children with INS seriously affect their physical and mental health and quality of life. Most children with steroid-sensitive nephrotic syndrome can be cured before adulthood, while some of them relapse in adulthood. Long-term prognosis of children with steroid-resistant nephrotic syndrome is poor. There have been few studies in China followed the long-term outcomes and its related factors of children with INS over 10 years. The paper reviewed the literatures on the long-term outcomes of children with INS, including renal survival, growth, mental health, learning and work, marriage and fertility, disease recurrence and long-term related complications, to explore the factors related to the poor long-term outcomes of children with INS and to assist in clinical decision-making and follow-up management.