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.

ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）. ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

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 effect of body position angle on gastric insufflation during the induction of general anesthesia in pediatric patients undergoing day surgery.Methods A total of 111 children scheduled for elective tracheal intubation under general anesthesia at the First Affiliated Hospital of Guangxi Medical University from December 2022 to March 2023 were selected as study subjects.Six children were ex-cluded due to unclear sonographic visualization of the gastric antrum,resulting in 105 children ultimately in-cluded in the study.The children were divided into three groups using a random number table method:Group D0(supine position),Group D5(5° head-up position),and Group D10(10° head-up position),with 35 children in each group.The presence of a"comet-tail artifact"on ultrasound was used as the criterion for determining gastric insufflation during anesthesia induction.The gastric antrum cross-sectional area(CSA)of the gastric antrum was measured before mask ventilation after loss of consciousness(T1)and immediately after tracheal intubation following mask ventilation(T2).The incidence of gastric insufflation,changes in CSA and their differences,and vital sign changes at T1 and T2,were compared among the three groups.Results Compared with Group D0,the incidence of gastric insufflation was significantly lower in Groups D5 and D10[25.7％(9/35)vs.20.0％(7/35)vs.54.0％(19/35)],and the difference was statistically significant(P＜0.05).Howev-er,there was no significant difference between Group D5 and Group D10(P＞0.05).No significant difference was observed in CSA at T1 among the three groups(P＞0.05).At T2,a statistically significant difference in CSA was found among the three groups(P＜0.05),with Group D10 showing a smaller CSA than Group D0(P＜0.05).The difference in CSA changes was statistically significant among the three groups(P＜0.05),with Groups D5 and D10 exhibiting smaller changes than Group D0,and Group D10 showing a smaller change than Group D5(P＜0.05).No significant differences were observed in mean artery pressure(MAP),heart rate,pulse oxygen saturation(SpO2)and pressure of end-tidal carbon dioxide(PETCO2)at T1 and T2 among the three groups(P＞0.05).A total of 6 children(5.7％)required brief adjustments in jaw support due to irregular PETCO2 waveforms or abnormal peak airway pressure.Conclusion In pediatric patients undergoing day sur-gery under general anesthesia,a 5° head-up position during induction significantly reduces the incidence of gas-tric insufflation and minimizes changes in gastric antral CSA,while a 10° head-up position does not provide ad-ditional benefits.

OBJECTIVE To analyze the value of elastic modulus of shear wave elastography in the diagnosis of cervical lymph node metastasis of thyroid cancer and its correlation with VEGF-C and VEGF-D.METHODS A total of 120 patients with thyroid cancer admitted to our hospital were divided into metastatic group(n=37)and non-metastatic group(n=83)according to whether the cervical lymph node metastasis.The clinical data and SWE elastic modulus values of the two groups were compared,and the effects of clinical characteristics on SWE elastic modulus values were analyzed by hierarchical regression.Logistic regression analysis was conducted to analyze the independent correlation between SWE elastic modulus and the risk of lymph node metastasis of thyroid cancer.The dose-response relationship between the elastic modulus of SWE and the risk of lymph node metastasis in thyroid cancer was analyzed with restricted cubic strips.The correlation between SWE elastic modulus and VEGF-C and D levels was analyzed after adjusting factors by Logistic regression.RESULTS The results of general data analysis showed that male proportion,BMI,clinical stage,lesion diameter,TSH,FT4,TgAb positive rate,TPOAb positive rate,VEGF-C and VEGF-D in metastatic group were higher than those in non-metastatic group.Under different clinical characteristics,SWE parameters Emax,Emean and Eratio in metastatic group were higher than those in non-metastatic group.In hierarchical regression analysis,gender,clinical stage,lesion diameter,biochemical indices(TSH,FT4,TgAb,TPOAb)had significant positive effects on SWE parameters.SWE parameters were independently associated with the risk of lymph node metastasis of thyroid cancer.Subgroup analysis showed that the association between SWE parameters and the risk of lymph node metastasis of thyroid cancer in all subgroups was statistically significant(P<0.05).There was no nonlinear dose-response relationship between SWE parameters and thyroid cancer risk(P>0.05).After adjusting for confounding factors,there was a significant linear correlation between Emax,Emean,Eratio and VEGF-C and VEGF-D(P<0.05).CONCLUSION The elastic modulus of SWE has a certain diagnostic value for lymph node metastasis of thyroid cancer,and SWE parameters have a certain correlation with VEGF-C and VEGF-D.

Objective To isolate endophytic fungi from Angelica sinensis and evaluate the bioactivity of their secondary metabolites.Methods Angelica sinensis and rhizosphere soil were utilized as materials.The tissue homogenization method was employed with six diverse culture media to isolate endophytic fungi.The antibacterial activity of secondary metabolites was gauged using a 96-well plate assay,while UV spectrophotometry was used to evaluate the inhibitory activity of four enzymes.Results A total of 153 fungal strains were isolated and purified from Angelica sinensis roots,stems,leaves,and soil.The samples exhibited specific inhibitory activities against adenosine deaminase(ADA),β-lactamase,xanthine oxidase(XO),and tyrosinase(TYR),with rates of 45.83%,52.78%,51.39%and 55.56%,respectively.Furthermore,1.39%of the samples displayed wide-ranging inhibitory effects against four indicator bacteria.Strain 6B also showcased the lowest inhibitory concentration values of 62.5 and 7.81 μg/mL against Escherichia coli ATCC25922 and ATCC35218,respectively,signifying its potential research significance.Conclusion Angelica sinensis has abundant endophytic fungal resources and is a good source for discovering active compounds,demonstrating certain research value.

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. 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 N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

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.