ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

Risk prediction models for postoperative pulmonary complications (PPCs) can assist healthcare professionals in assessing the likelihood of PPCs occurring after surgery, thereby supporting rapid decision-making. This study evaluated the merits, limitations, and challenges of these models, focusing on model types, construction methods, performance, and clinical applications. The findings indicate that current risk prediction models for PPCs following lung cancer surgery demonstrate a certain level of predictive effectiveness. However, there are notable deficiencies in study design, clinical implementation, and reporting transparency. Future research should prioritize large-scale, prospective, multi-center studies that utilize multiomics approaches to ensure robust data for accurate predictions, ultimately facilitating clinical translation, adoption, and promotion.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD)on the efficacy of M1 bone marrow-derived macrophages(M1-BMDMs)in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4.Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide.A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats.The rats for modeling were given subcutaneous injection of 50%CCl4 twice a week.Since week 7,the rats for modeling were randomly divided into model group(M group),YGJD group,M1-BMDM group,M1-BMDM+YGJD group,and sorafenib(SORA)group,and they were given subcutaneous injection of 30%CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF.CCR2 inhibitors were added to the drinking water,and each group was given the corresponding intervention.Related samples were collected at week 9.The rats were observed in terms of serum liver function parameters,liver pathology,hydroxyproline(Hyp)content in liver tissue,hepatic stellate cell activation,hepatic fibrosis and inflammation factors,and the expression levels of molecules associated with the Wnt signaling pathway.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the M group,the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin(TBil)(all P<0.05)and a significant increase in the content of albumin(Alb)(P<0.05),and compared with the M1-BMDM group,the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05)and a significant increase in the serum level of Alb(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05).As for the non-canonical Wnt signaling pathway molecules,compared with the M1-BMDM group,the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P<0.05)and mRNA expression level of Fzd2(P<0.05),as well as significant reductions in the mRNA expression levels of Wnt4,Wnt5b,and Fzd3(P<0.05),while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin,LRP5,LRP6,Fzd5,and TCF.Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4,possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway,which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.