ObjectiveTo construct and evaluate various machine learning models for predicting the risk of chronic obstructive pulmonary disease （COPD） in individuals， thereby providing data support for early screening and intervention. MethodsA total of 823 subjects were selected for this study， comprising 142 individuals in the high-risk group for COPD and 681 individuals in the low-risk group. Data collected included demographic characteristics， smoking history， symptoms （such as cough and shortness of breath）， and scores from the Chronic obstructive pulmonary disease screening questionnaire. Four machine learning algorithms—Logistic regression， random forest， support vector machine， and XGBoost—were utilized to construct risk prediction models. The performance of these models was assessed using 5-fold cross-validation， with evaluation metrics including accuracy， precision， recall， F1-score， area under the receiver operating characteristic curve （AUC）， and average precision （AP）. Furthermore， a feature importance analysis was performed. ResultsThe Logistic Regression model exhibited superior performance， achieving an AUC of 0.982 and an AP of 0.939. This was closely followed by the Random Forest model， which recorded an AUC of 0.975 and an AP of 0.890. Feature importance analysis revealed that smoking history， symptoms of shortness of breath， and body weight were significant predictors. All models demonstrated robust performance in identifying low-risk populations； however， variations were observed in their efficacy in identifying high-risk populations. ConclusionMachine learning models have proven effective in identifying individuals at high risk for COPD. Among these， the Logistic regression model exhibits the best overall performance， efficiently identifying high-risk populations and serving as a valuable clinical auxiliary screening tool. Various models， each with distinct performance characteristics， are suited to different clinical screening scenarios， thereby offering targeted decision-making support for the establishment of a hierarchical and intelligent COPD screening pathway.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

BACKGROUND:A large number of cell and animal tests have confirmed the effect of mesenchymal stem cells on improving ovarian function,and some clinical trials have been completed and their effectiveness has been preliminarily confirmed,bringing hope to women with premature ovarian failure.OBJECTIVE:To summarize and analyze the mechanism,research progress,and related clinical trials of mesenchymal stem cells from different sources in the treatment of premature ovarian failure in recent years,so as to provide a theoretical basis for further research and clinical application of mesenchymal stem cell therapy for premature ovarian failure.METHODS:Using "mesenchymal stem cells,premature ovarian failure" as keywords in Chinese and English,the relevant literature was searched in CNKI,WanFang Data,Chinese Medical Database,and PubMed database,and finally 72 articles that met the requirements were included for review.RESULTS AND CONCLUSION:Currently,there are seven types of commonly used mesenchymal stem cells for premature ovarian failure,which are umbilical cord mesenchymal stem cells,bone marrow mesenchymal stem cells,placental mesenchymal stem cells,menstrual blood mesenchymal stem cells,amniotic mesenchymal stem cells,amniotic fluid mesenchymal stem cells,and adipose mesenchymal stem cells.The mechanisms include inhibiting apoptosis and promoting proliferation,anti-inflammatory and inhibiting oxidative stress,homing,promoting angiogenesis,anti-fibrosis,parasecretory,immune regulation,autophagy,and improving microenvironment.Cell and animal experiments have proven that different sources of mesenchymal stem cells can have better intervention effect on premature ovarian failure through various mechanisms,and delay the progress of premature ovarian failure to a certain extent.If it can be successfully applied to the clinic in the future,it can alleviate the psychological and physical pain of patients to a great extent.However,due to the lack of comprehensive and accurate evidence in clinical studies such as stem cell source,administration mode and dose,adverse reactions,etc.,further studies are still needed to confirm it in the future,and its long-term safety needs to be further observed.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

BACKGROUND:A large number of cell and animal tests have confirmed the effect of mesenchymal stem cells on improving ovarian function,and some clinical trials have been completed and their effectiveness has been preliminarily confirmed,bringing hope to women with premature ovarian failure.OBJECTIVE:To summarize and analyze the mechanism,research progress,and related clinical trials of mesenchymal stem cells from different sources in the treatment of premature ovarian failure in recent years,so as to provide a theoretical basis for further research and clinical application of mesenchymal stem cell therapy for premature ovarian failure.METHODS:Using "mesenchymal stem cells,premature ovarian failure" as keywords in Chinese and English,the relevant literature was searched in CNKI,WanFang Data,Chinese Medical Database,and PubMed database,and finally 72 articles that met the requirements were included for review.RESULTS AND CONCLUSION:Currently,there are seven types of commonly used mesenchymal stem cells for premature ovarian failure,which are umbilical cord mesenchymal stem cells,bone marrow mesenchymal stem cells,placental mesenchymal stem cells,menstrual blood mesenchymal stem cells,amniotic mesenchymal stem cells,amniotic fluid mesenchymal stem cells,and adipose mesenchymal stem cells.The mechanisms include inhibiting apoptosis and promoting proliferation,anti-inflammatory and inhibiting oxidative stress,homing,promoting angiogenesis,anti-fibrosis,parasecretory,immune regulation,autophagy,and improving microenvironment.Cell and animal experiments have proven that different sources of mesenchymal stem cells can have better intervention effect on premature ovarian failure through various mechanisms,and delay the progress of premature ovarian failure to a certain extent.If it can be successfully applied to the clinic in the future,it can alleviate the psychological and physical pain of patients to a great extent.However,due to the lack of comprehensive and accurate evidence in clinical studies such as stem cell source,administration mode and dose,adverse reactions,etc.,further studies are still needed to confirm it in the future,and its long-term safety needs to be further observed.

Objective A porcine vocal cord injury model was established to analyze and compare the damage range of porcine vocal cords and the repair process after vocal cord injury caused by CO2 laser surgery and radiofre-quency ablation with plasma spot excitation technology.Methods Fifteen pigs,30 sides of vocal cords,were used in this study.The bilateral vocal cords of the same pig were divided into CO2 laser and radiofrequency coblation(RFC)groups respectively.CO2 laser and radiofrequency ablation with plasma spot excitation technology were used to perform ubligamental cordectomy.Three pigs were sacrificed after anesthesia on postoperative day 1 and postop-erative 3,6,9,and 15 weeks.The vocal cords were harvested for HE staining.The depth of edema degeneration zone and the fibrous tissue thickness were measured vertically in the two groups,and the postoperative vocal cord damage range and vocal cord repair process were compared between the two groups.Results The depth of edema degeneration zone in the CO2 laser group was deeper than that in the RFC group at 1 day postoperatively(P＜0.01).There was no significant difference in the depth of the edema degeneration zone between the two groups at the 3rd,6th,and 9th weeks after operation(P＞0.05).The depth of the edema degeneration zone at 3rd weeks postoperatively was less than that at 1 day postoperatively,and at 6th weeks postoperatively was less than that at 3rd weeks postoperatively for both operation modes(P＜0.05).There was no statistically significant difference be-tween 9th weeks postoperatively and 6th weeks postoperatively(P＞0.05).At the 15th week after operation,the fibrous tissue thickness of the vocal fold lamina propria in the RFC group was thinner than that in the CO2 laser group(P＜0.01).Conclusion Radiofrequency ablation with plasma spot excitation technology causes less damage to porcine vocal fold than CO2 laser.There is no significant difference between the two operation modes in terms of postoperative repair process,while the fibrous tissue in the lamina propria of the vocal fold is thinner in the RFC group when a vocal fold scar is formed.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway. CONCLUSION This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Objective To investigate the inhibitory effect and molecular mechanism of Huaier granule on the growth of sorafenib resistant hepatocellular carcinoma (HCC) cells. Methods The gradient concentration of Huaier granule was used to treat HCC cells, and the effect of Huaier granule on the proliferation, migration and invasion of sorafenib resistant HCC cells was analyzed. Bioinformatics methods were used to analyze the possible interaction between microRNA-31-5p (miR-31-5p) and sprouty-related proteins with an EVH1 domain 1 (SPRED1). The expression levels of miR-31-5p and SPRED1 in HCC cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR); cell viability, proliferation, migration, invasion and apoptosis were detected by CCK-8, colony formation, scratch healing, Transwell and flow cytometry; RNA immunoprecipitation (RIP) assay and dual luciferase assay were used to verify the binding relationship between miR-31-5p and SPRED1. Results Huaier granule could significantly inhibit the proliferation, migration and invasion of sorafenib resistant HCC cells, and induce apoptosis. Bioinformatics analysis showed that miR-31-5p was highly expressed in HCC, and Huaier granule was able to down-regulate the expression of miR-31-5p, inhibit the proliferation and metastasis of sorafenib resistant HCC cells, and induce apoptosis; miR-31-5p showed a targeted inhibition effect on the expression of SPRED1. SPRED1 was down-regulated in HCC, and overexpression of SPRED1 was able to reverse the promoting effect of overexpression of miR-31-5p on proliferation and metastasis of sorafenib resistant HCC. Conclusion Huaier granule can inhibit sorafenib resistant HCC metastasis through the miR-31-5p/SPRED1 axis, indicating that Huaier granule has the potential to be used as a novel drug for HCC treatment.

Ex vivo-expanded mesenchymal stem cells(MSCs)have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative,multipotential,and immunomodu-latory capacities.However,the exact characteristics of MSCs remain largely unknown.By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly,we revealed five distinct subpopulations.The developmental trajectory of these five MSC subpopulations was mapped,revealing a differentiation path from stem-like active proliferative cells(APCs)to multipotent progenitor cells,followed by branching into two paths:1)unipotent preadipocytes or 2)bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondro-cytes.The stem-like APCs,expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES,uniquely exhibited strong proliferation and stemness signatures.Remarkably,the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to sup-press activated CD3+T cell proliferation in vitro,supporting the role of this population in immunoregulation.In summary,our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation.Our findings advance the definition of MSCs by identifying the specific functions of their heteroge-neous cellular composition,allowing for more specific and effective MSC application through the purification of their functional subpopulations.

OBJECTIVE： To prepare Zingiber officinale oil microcapsules and to evaluate its quality. METHODS： Z. officinale oil microcapsules were prepared by spray drying method with sodium starch octenyl succinate as capsule material. The preparation technology was optimized by orthogonal test with mixing temperature of capsule material and capsule core， mass ratio of capsule material and capsule core， stirring speed as factors， using encapsulation efficiency as index. The drug loading， encapsulation efficiency， appearance， particle size distribution and stability of light， heat and humidity （using iodine value and peroxide value as indexes） were evaluated. RESULTS： The optimal preparation technology of Z. officinale oil microcapsules was that the mixing temperature of capsule material and core was 60 ℃； mass ratio of capsule material and capsule core was 10 ∶ 1； stirring speed was 12 000 r/min. Average drug-loading amount and encapsulation efficiency of Z. officinale oil microcapsules prepared by optimal technology were 17.97％ and 73.57％ （n＝3）. The morphology of Z. officinale oil microcapsules was round， smooth， non-sticky and uniform in size distribution. The average diameter of microcapsules was （6.30±0.27） μm. Under light， heat and humidity conditions， the iodine value and peroxide value of Z. officinale oil microcapsules changed slightly. CONCLUSIONS： The optimal preparation technology of Z. officinale oil microcapsules is simple and reproducible. The prepared microcapsules have good encapsulation efficiency， high drug loading amount and good stability.