OBJECTIVE:Premature ovarian failure has manifested a trend of younger,and stem cell therapy has been progressively implemented in clinical practice in recent years.Nevertheless,given the extensive range of sources and variegated existence of stem cells in diverse tissues,certain disparities prevail in their biological characteristics and functions.In this paper,the therapeutic efficacies of dissimilar sources of mesenchymal stem cells on animal models of premature ovarian failure were contrasted,with the aim of providing a basis for the clinical application of stem cells.METHODS:The animal model experiments of mesenchymal stem cell therapy for premature ovarian failure were retrieved from PubMed,The Cochrane Library,and EMbase,as well as Chinese databases such as CNKI,WanFang,VIP,and China Biomedical Literature Service.The search period extended from the inception to December 31,2023.Two researchers independently screened the literature,extracted and analyzed the data.The quality of the included studies was evaluated by means of the SYRCLE animal experiment bias risk assessment table.Main outcome measures:Follicle stimulating hormone,estradiol,luteinizing hormone,the quantity of follicles at all levels.Secondary outcome measure:Pregnancy rate.Network meta-analysis,mapping,and tabulation were executed using Stata 17.0 software after assessing the risk of bias in the included studies.RESULTS:Totally 24 animal experiment studies were incorporated,and the overall quality of the literature was mediocre,encompassing 7 distinct sources of mesenchymal stem cells.They were umbilical cord-derived mesenchymal stem cells,menstrual blood-derived mesenchymal stem cells,placenta-derived mesenchymal stem cells,human cord blood-derived mesenchymal stem cells,bone marrow-derived mesenchymal stem cells,adipose-derived mesenchymal stem cells,and amnio-derived mesenchymal stem cells.The network meta-analysis demonstrated that(1)in contrast to the blank group,mesenchymal stem cells from various sources were effective in enhancing the pregnancy rate and estradiol,reducing follicle-stimulating hormone and luteinizing hormone,augmenting the number of follicles at all levels,and diminishing the number of atretic follicles.(2)According to the area map under the cumulative sequencing curve,the three stem cells with the most prominent efficacy in improving estradiol levels were umbilical cord-derived mesenchymal stem cells(72.7％)＞adipose-derived mesenchymal stem cells(72.6％)＞menstrual blood-derived mesenchymal stem cells(71.7％).(3)The three kinds of stem cells with the highest efficacy in reducing follicle-stimulating hormone levels were the adipose-derived mesenchymal stem cells(96.3％)＞human cord blood-derived mesenchymal stem cells(65.4％)＞umbilical cord-derived mesenchymal stem cells(63.9％).(4)The three kinds of stem cells with the highest efficacy in reducing luteinizing hormone levels were adipose-derived mesenchymal stem cells(100.0％)＞umbilical cord-derived mesenchymal stem cells(51.6％)＞human cord blood-derived mesenchymal stem cells(46.8％).(5)The top three kinds of stem cells for increasing the number of primordial follicles were human cord blood-derived mesenchymal stem cells(76.3％)＞umbilical cord-derived mesenchymal stem cells(75.5％)＞menstrual blood-derived mesenchymal stem cells(57.5％).(6)The top three kinds of stem cells for increasing the number of primary follicles were umbilical cord-derived mesenchymal stem cells(75.3％)＞adipose-derived mesenchymal stem cells(53.0％)＞the placenta-derived mesenchymal stem cells(51.7％).(7)The top three kinds of stem cells for increasing the number of secondary follicles were adipose-derived mesenchymal stem cells(76.1％)＞menstrual blood-derived mesenchymal stem cells(66.8％)＞umbilical cord-derived mesenchymal stem cells(66.5％).(8)The top three kinds of stem cells in reducing the number of atretic follicles were adipose-derived mesenchymal stem cells(99.9％)＞bone marrow-derived mesenchymal stem cells(68.1％)＞umbilical cord-derived mesenchymal stem cells(53.4％).CONCLUSION:(1)For animal models of premature ovarian failure,the results of the network meta-analysis disclosed that various stem cell transplantation treatments were preponderant over the blank or placebo group to varying extents,and the efficacies were comparable.(2)The results indicated that umbilical cord-derived mesenchymal stem cells were the most frequently utilized and adipose-derived mesenchymal stem cells were the most potent.More high-quality experimental study data are requisite in the future for further validation.

Objective To elucidate the effects and mechanisms of Biejiajian pill(BJJP)-containing serum on the malignant biological behaviors of hepatocellular carcinoma Huh7 cells.Methods This research knocked down CKLF-like MARVEL transmembrane domain containing 6(CMTM6)expression using a CMTM6-specific small interfering RNA(siRNA).Healthy Sprague-Dawley rats were used to prepare normal rat serum and low-(0.55 g/kg),medium-(1.1 g/kg),and high-(2.2 g/kg)BJJP-containing.Huh7 cells were cultured with normal fetal bovine serum(BC),normal rat serum(NC),and low-,medium-,and high-dose BJJP serum(LBJJP,MBJJP,and HBJJP,respectively).BJJP-containing serum and si-CMTM6 were applied to Huh7 cancer cells,and the proliferation,migration,and invasion abilities were evaluated by CCK-8 and Transwell assays,respectively.Protein expression levels of proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)markers,and CMTM6 were detected by Western blot.Results CMTM6 knockdown significantly reduced the mRNA and protein expression level of CMTM6 in Huh7 cells(P＜0.05).There were no significant differences between the BC and NC groups in terms of cell proliferation,migration,invasion,expression levels of PCNA,EMT markers,and CMTM6(all P＞0.05).BJJP-containing serum markedly inhibited Huh7 cell proliferation,migration,and invasion(P＜0.05),downregulated PCNA,CMTM6,N-cadherin,and Vimentin expression,and upregulated E-cadherin compared with the NC group(all P＜0.05).CMTM6 knockdown suppressed malignant behaviors,with reduced PCNA,Vimentin,and N-cadherin and elevated E-cadherin expression(all P＜0.05).Conclusions BJJP-containing serum can significantly inhibit Huh7 cell growth,invasion,migration,and EMT progression,potentially mediated via CMTM6 suppression.

Objective To investigate the effect of Biejiajian Pill(BJJP)on malignant biological behavior of hepatocellular carcinoma Hep3B cells and its regulatory mechanism.Methods A total of 72 healthy SD rats were randomly divided into blank control(BC)group,low(0.55 g/kg),medium(1.10 g/kg)and high(2.20 g/kg)BJJP experimental group,and drug-containing serum was prepared.Hep3B cells were divided into BC group,normal rat serum treatment(NC)group,low dose BJJP(LBJJP)group,medium dose BJJP(MBJJP)group and high dose BJJP(HBJJP)group,empty plasmid(pcDNA3.1)group,and CKLF-like MARVEL transmembrane domain containing 6(CMTM6)overexpression(pcDNA3.1-CMTM6)group,and the NC+pcDNA3.1 group,MBJJP+pcDNA3.1 group,NC+pcDNA3.1-CMTM6 group and MBJJP+pcDNA3.1-CMTM6 group.The proliferation of hepatoma Hep3B cells was detected by CCK-8.The migration and invasion of hepatoma Hep3B cells were detected by Transwell assay.The expression levels of proliferation-related proteins proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,N-cadherin and Vimentin),and CMTM6 proteins in hepatoma Hep3B cells were detected by Western blotting experiments.Results Compared with those in BC group,there were no significant differences in the proliferation,migration and invasion abilities of Hep3B cells,or the expression levels of PCNA,EMT related proteins(E-cadherin,N-cadherin and Vimentin)and CMTM6 protein in NC group(P＞0.05).Compared with NC group,LBJJP,MBJJP and HBJJP drug-containing serum inhibited the proliferation,migration and invasion of Hep3B cells,downregulated the protein expression of PCNA;MBJJP and HBJJP upregulated the protein expression of E-cadherin.The protein expressions of N-cadherin,Vimentin and CMTM6 were downregulated,with significant differences(P＜0.05).Compared with pcDNA3.1 group,the protein expression of CMTM6,cell proliferation,migration,invasion,PCNA protein expression,N-cadherin protein expression,and Vimentin protein expression in Hep3B cells in pcDNA3.1-CMTM6 group were significantly upregulated,while the protein expression of E-cadherin was significantly downregulated(P＜0.05).Compared with NC+pcDNA3.1 group,the proliferation,migration and invasion abilities of Hep3B cells in MBJJP+pcDNA3.1 group were decreased,the expression levels of PCNA,Vimentin and N-cadherin protein were decreased,while the expression level of E-cadherin protein was increased.Compared with NC+pcDNA3.1-CMTM6 group,MBJJP+pcDNA3.1-CMTM6 group had the same results in the proliferation,migration and invasion abilities of Hep3B cells and the protein expression levels of PCNA,Vimentin,N-cadherin and E-cadherin.The differences were statistically significant(all P＜0.05).Conclusion BJJP may inhibit the proliferation,migration,invasion and EMT of hepatoma Hep3B cells by regulating the expression of CMTM6.

Objective To elucidate the effects and mechanisms of Biejiajian pill(BJJP)-containing serum on the malignant biological behaviors of hepatocellular carcinoma Huh7 cells.Methods This research knocked down CKLF-like MARVEL transmembrane domain containing 6(CMTM6)expression using a CMTM6-specific small interfering RNA(siRNA).Healthy Sprague-Dawley rats were used to prepare normal rat serum and low-(0.55 g/kg),medium-(1.1 g/kg),and high-(2.2 g/kg)BJJP-containing.Huh7 cells were cultured with normal fetal bovine serum(BC),normal rat serum(NC),and low-,medium-,and high-dose BJJP serum(LBJJP,MBJJP,and HBJJP,respectively).BJJP-containing serum and si-CMTM6 were applied to Huh7 cancer cells,and the proliferation,migration,and invasion abilities were evaluated by CCK-8 and Transwell assays,respectively.Protein expression levels of proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)markers,and CMTM6 were detected by Western blot.Results CMTM6 knockdown significantly reduced the mRNA and protein expression level of CMTM6 in Huh7 cells(P＜0.05).There were no significant differences between the BC and NC groups in terms of cell proliferation,migration,invasion,expression levels of PCNA,EMT markers,and CMTM6(all P＞0.05).BJJP-containing serum markedly inhibited Huh7 cell proliferation,migration,and invasion(P＜0.05),downregulated PCNA,CMTM6,N-cadherin,and Vimentin expression,and upregulated E-cadherin compared with the NC group(all P＜0.05).CMTM6 knockdown suppressed malignant behaviors,with reduced PCNA,Vimentin,and N-cadherin and elevated E-cadherin expression(all P＜0.05).Conclusions BJJP-containing serum can significantly inhibit Huh7 cell growth,invasion,migration,and EMT progression,potentially mediated via CMTM6 suppression.

Objective To investigate the effect of Biejiajian Pill(BJJP)on malignant biological behavior of hepatocellular carcinoma Hep3B cells and its regulatory mechanism.Methods A total of 72 healthy SD rats were randomly divided into blank control(BC)group,low(0.55 g/kg),medium(1.10 g/kg)and high(2.20 g/kg)BJJP experimental group,and drug-containing serum was prepared.Hep3B cells were divided into BC group,normal rat serum treatment(NC)group,low dose BJJP(LBJJP)group,medium dose BJJP(MBJJP)group and high dose BJJP(HBJJP)group,empty plasmid(pcDNA3.1)group,and CKLF-like MARVEL transmembrane domain containing 6(CMTM6)overexpression(pcDNA3.1-CMTM6)group,and the NC+pcDNA3.1 group,MBJJP+pcDNA3.1 group,NC+pcDNA3.1-CMTM6 group and MBJJP+pcDNA3.1-CMTM6 group.The proliferation of hepatoma Hep3B cells was detected by CCK-8.The migration and invasion of hepatoma Hep3B cells were detected by Transwell assay.The expression levels of proliferation-related proteins proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,N-cadherin and Vimentin),and CMTM6 proteins in hepatoma Hep3B cells were detected by Western blotting experiments.Results Compared with those in BC group,there were no significant differences in the proliferation,migration and invasion abilities of Hep3B cells,or the expression levels of PCNA,EMT related proteins(E-cadherin,N-cadherin and Vimentin)and CMTM6 protein in NC group(P＞0.05).Compared with NC group,LBJJP,MBJJP and HBJJP drug-containing serum inhibited the proliferation,migration and invasion of Hep3B cells,downregulated the protein expression of PCNA;MBJJP and HBJJP upregulated the protein expression of E-cadherin.The protein expressions of N-cadherin,Vimentin and CMTM6 were downregulated,with significant differences(P＜0.05).Compared with pcDNA3.1 group,the protein expression of CMTM6,cell proliferation,migration,invasion,PCNA protein expression,N-cadherin protein expression,and Vimentin protein expression in Hep3B cells in pcDNA3.1-CMTM6 group were significantly upregulated,while the protein expression of E-cadherin was significantly downregulated(P＜0.05).Compared with NC+pcDNA3.1 group,the proliferation,migration and invasion abilities of Hep3B cells in MBJJP+pcDNA3.1 group were decreased,the expression levels of PCNA,Vimentin and N-cadherin protein were decreased,while the expression level of E-cadherin protein was increased.Compared with NC+pcDNA3.1-CMTM6 group,MBJJP+pcDNA3.1-CMTM6 group had the same results in the proliferation,migration and invasion abilities of Hep3B cells and the protein expression levels of PCNA,Vimentin,N-cadherin and E-cadherin.The differences were statistically significant(all P＜0.05).Conclusion BJJP may inhibit the proliferation,migration,invasion and EMT of hepatoma Hep3B cells by regulating the expression of CMTM6.

OBJECTIVE:Premature ovarian failure has manifested a trend of younger,and stem cell therapy has been progressively implemented in clinical practice in recent years.Nevertheless,given the extensive range of sources and variegated existence of stem cells in diverse tissues,certain disparities prevail in their biological characteristics and functions.In this paper,the therapeutic efficacies of dissimilar sources of mesenchymal stem cells on animal models of premature ovarian failure were contrasted,with the aim of providing a basis for the clinical application of stem cells.METHODS:The animal model experiments of mesenchymal stem cell therapy for premature ovarian failure were retrieved from PubMed,The Cochrane Library,and EMbase,as well as Chinese databases such as CNKI,WanFang,VIP,and China Biomedical Literature Service.The search period extended from the inception to December 31,2023.Two researchers independently screened the literature,extracted and analyzed the data.The quality of the included studies was evaluated by means of the SYRCLE animal experiment bias risk assessment table.Main outcome measures:Follicle stimulating hormone,estradiol,luteinizing hormone,the quantity of follicles at all levels.Secondary outcome measure:Pregnancy rate.Network meta-analysis,mapping,and tabulation were executed using Stata 17.0 software after assessing the risk of bias in the included studies.RESULTS:Totally 24 animal experiment studies were incorporated,and the overall quality of the literature was mediocre,encompassing 7 distinct sources of mesenchymal stem cells.They were umbilical cord-derived mesenchymal stem cells,menstrual blood-derived mesenchymal stem cells,placenta-derived mesenchymal stem cells,human cord blood-derived mesenchymal stem cells,bone marrow-derived mesenchymal stem cells,adipose-derived mesenchymal stem cells,and amnio-derived mesenchymal stem cells.The network meta-analysis demonstrated that(1)in contrast to the blank group,mesenchymal stem cells from various sources were effective in enhancing the pregnancy rate and estradiol,reducing follicle-stimulating hormone and luteinizing hormone,augmenting the number of follicles at all levels,and diminishing the number of atretic follicles.(2)According to the area map under the cumulative sequencing curve,the three stem cells with the most prominent efficacy in improving estradiol levels were umbilical cord-derived mesenchymal stem cells(72.7％)＞adipose-derived mesenchymal stem cells(72.6％)＞menstrual blood-derived mesenchymal stem cells(71.7％).(3)The three kinds of stem cells with the highest efficacy in reducing follicle-stimulating hormone levels were the adipose-derived mesenchymal stem cells(96.3％)＞human cord blood-derived mesenchymal stem cells(65.4％)＞umbilical cord-derived mesenchymal stem cells(63.9％).(4)The three kinds of stem cells with the highest efficacy in reducing luteinizing hormone levels were adipose-derived mesenchymal stem cells(100.0％)＞umbilical cord-derived mesenchymal stem cells(51.6％)＞human cord blood-derived mesenchymal stem cells(46.8％).(5)The top three kinds of stem cells for increasing the number of primordial follicles were human cord blood-derived mesenchymal stem cells(76.3％)＞umbilical cord-derived mesenchymal stem cells(75.5％)＞menstrual blood-derived mesenchymal stem cells(57.5％).(6)The top three kinds of stem cells for increasing the number of primary follicles were umbilical cord-derived mesenchymal stem cells(75.3％)＞adipose-derived mesenchymal stem cells(53.0％)＞the placenta-derived mesenchymal stem cells(51.7％).(7)The top three kinds of stem cells for increasing the number of secondary follicles were adipose-derived mesenchymal stem cells(76.1％)＞menstrual blood-derived mesenchymal stem cells(66.8％)＞umbilical cord-derived mesenchymal stem cells(66.5％).(8)The top three kinds of stem cells in reducing the number of atretic follicles were adipose-derived mesenchymal stem cells(99.9％)＞bone marrow-derived mesenchymal stem cells(68.1％)＞umbilical cord-derived mesenchymal stem cells(53.4％).CONCLUSION:(1)For animal models of premature ovarian failure,the results of the network meta-analysis disclosed that various stem cell transplantation treatments were preponderant over the blank or placebo group to varying extents,and the efficacies were comparable.(2)The results indicated that umbilical cord-derived mesenchymal stem cells were the most frequently utilized and adipose-derived mesenchymal stem cells were the most potent.More high-quality experimental study data are requisite in the future for further validation.

Objective To observe whether the IL-23/Th17 inflammatory pathway is involved in the development of calcific aortic valve disease,and whether secukinumab can delay the progression of calcific aortic valve disease by inhibiting this pathway.Methods Forty-seven mice were divided into a blank control group,model group,and secukinumab group according to the random number table method.The blank control group was fed normal chow,while the model group and secukinumab group were fed pro-calcification chow for 16 weeks to establish a calcific aortic valve disease model.After intervention with secukinumab for 4 weeks,peak flow velocity changes in the aortic valves were detected under Doppler ultrasonography in all mice.Relevant indexes were determined by hematoxylin and eosin staining,Von Kossa staining,immunohistochemical staining,ELISA,and qPCR.Results Compared with the model group,the secukinumab group showed significantly reduced peak flow velocity(P＜0.05)and serum IL-6,IL-17,and IL-23 levels(P＜0.05)in the aortic valve.Compared with the secukinumab group,the model group's leaflet thickness was significantly increased,and there were more calcium deposits.Immunohistochemical result showed that macrophage infiltration(P＜0.05),IL-17A(P＜0.05)and IL-23(P＞0.05)levels in the valve leaflets were reduced in the secukinumab group compared with the model group.PCR result suggested that the expression of STAT3,BMP-2,and α-SMA mRNA was significantly lower in the secukinumab group than the model group(P＜0.05).Conclusions The IL-23/Th17 inflammatory pathway is involved in the pathogenesis of calcific aortic valve disease.The inflammation,fibrosis,osteogenic differentiation,and calcification of mouse valves were alleviated after intervention with secukinumab,which may delay disease progression by inhibiting the IL-23/Th17 inflammatory pathway.

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

Objective:To investigate the effects of microRNA-10a(miR-10a)on the proliferation and migration of tumor-associated fibroblasts(TAFs)in the liver microenvironment, as well as on the mRNA expressions of interleukin(IL)-6, IL-8 and IL-1β in TAFs.Methods:The normal liver tissues adjacent to cancer and focal tissues of metastatic colon cancer to the liver from the same patient were collected, and then primary normal fibroblasts(NFs)and the primary cell line of TAFs were established by tissue cultivation.The NFs and TAFs were identified by morphological observation and immunofluorescence staining, and their purity was determined by flow cytometry.The real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of miR-10a in NFs and TAFs, and then miR-10a was over-expressed in the lower ones.Subsequently, the effects of miR-10a on cell proliferation, migration and the mRNA expression levels of IL-6, IL-8 and IL-1β were detected by the cholecystokinin(CCK-8)test, wound healing assay and RT-qPCR.Results:Immunofluorescence staining showed that human cytokeratin 18(CK-18)was neither expressed in NFs nor in TAFs, while fibroblast-specific protein 1(FSP-1)was expressed in NFs and TAFs, and alpha-smooth muscle actin(α-SMA)was weakly expressed in NFs but strongly expressed in TAFs.The results of flow cytometry showed that the positive rates of α-SMA in NFs and TAFs were 95.6% and 95.3%, respectively.The mRNA expression of miR-10a in TAFs was 0.65 times of that in NFs( P<0.01). After overexpression of miR-10a, the proliferation abilities at the 3th, 4th and 5th day were lower in TAFs than in NFs( P<0.05 and 0.01), the migration abilities at 24 h and 48 h were 25% and 15% lower in TAFs than in NF group( P<0.01 and 0.05), and the mRNA levels of IL-6, IL-8, IL-1 β were 54%, 27% and 42% lower in TAFs than in NFs, respectively( P<0.01, 0.01 and 0.05). Conclusions:The overexpression of miR-10a in TAFs inhibits the cell proliferation and migration and reduces the mRNA expressions of inflammatory factors IL-6, IL-8 and IL-1β, which may be an important factor for TAFs’ inhibiting liver metastasis.

Objective: To investigate the blood lead level of outpatient children and associated factors in Zhuzhou, and to offer targeted advice for the prevention and control of lead exposure. Methods: The lead level in blood of 1 600 children aged ≤14 years old and the content of serum calcium, iron, zinc, magnesium, copper were tested, and the children and their parents were given a questionnaire regarding influencing factors of blood lead exposure. Results: The average blood lead level of the children was (95.2±46.5)μg/L, The proportion of children with blood lead level ≥100 μg/L was 25.7%. The blood lead level between boys and girls had a statistical differences(Z=1.85, 2.85, P<0.05). The blood lead level was negatively correlated with serum calcium, iron, zinc, magnesium and copper(F=16.80，P<0.01). The risk factors for lead exposure included frequently drinking canned or bottled soft drinks, failing to wash one’s hands before meals, taking popcorn frequently, using coal for heat and for cooking, and constantly sucking fingers or biting fingernails (OR=2.12, 1.57, 1.46, 1.78, 3.24, P<0.01). Conclusion The blood lead levels of children in Zhuzhou is higher than national average level. We should strengthen environmental protection and behavioral interventions, and regularly monitor lead exposure among children.