ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.

ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.

Background:Acute pancreatitis(AP)is a common disease of the digestive system,among which severe acute pancreatitis(SAP)has a high mortality rate.Finding more accurate and convenient methods for early recognition of SAP is one of the major challenges in clinical treatment.Aims:To explore the application value of the controlled attenuation parameter(CAP)of ultrasound elastography in predicting SAP.Methods:A retrospective cohort study was conducted involving 135 AP patients admitted to Jiading Branch of Shanghai General Hospital from February to October 2024.Patients were categorized into non-SAP and SAP groups according to the severity of the disease.Clinical data,local complications,laboratory indicators,and CAP were compared between the two groups.Univariate and multivariate Logistic regression analyses were used to identify independent risk factors for SAP.A SAP prediction model based on CAP was constructed according to the identified risk factors and the minimum Akaike information criterion(AIC).ROC curve and Bootstrap method were used to evaluate the efficacy of the prediction model and conduct internal validation,respectively.Results:There were statistically significant differences between the non-SAP group and SAP group in body mass index(BMI),incidence of hyperlipidemia,etiological composition,incidence of pleural and ascitic fluid,length of hospital stay,incidence of peripancreatic effusion,incidence of pancreatic necrosis,white blood cell count(WBC),D-dimer(D-D)level,blood glucose,triglyceride(TG),C-reactive protein(CRP),neutrophil count,procalcitonin(PCT),interleukin-6(IL-6),free triiodothyronine(FT3),and CAP(all P<0.05).Multivariate Logistic regression analysis showed that pancreatic necrosis(OR=13.39,95%CI:3.10-57.94,P<0.001)and CAP(OR=1.01,95%CI:1.01-1.02,P=0.038)were independent risk factors for SAP.The SAP prediction model based on CAP was formulated as:Logit(P)=-5.884+0.010×CAP+2.839×pancreatic necrosis+0.169×D-D+0.132×blood glucose+0.006×CRP.The model showed an area under the curve(AUC)of 0.834 for predicting SAP,which was superior to CAP alone(P<0.05).Internal validation indicated that the prediction model had high stability and accuracy(C-index=0.808).Conclusions:The prediction model constructed based on CAP has good clinical value for predicting SAP,providing a new perspective and tool for early identification and prognostic assessment of AP.

Endometrial injury diseases are an important factors in female infertility, reduced menstruation, and adverse pregnancy outcomes. Clinical characteristics include intrauterine adhesions, a thin endometrium, and reduced endometrial receptivity. Restoring the morphology of the uterine cavity and promoting endometrial reconstruction are the main goals of treatment. At present, hormone medication and surgery are the major Western medicine treatments. Traditional Chinese Medicine has an advantage in treating endometrial injury and preventing postoperative recurrence. Traditional Chinese Medicine diagnosis focuses on "kidney deficiency" as the primary condition,"blood stasis" as the secondary condition, and combined with "liver depression". Therapeutic strategies aim to "replenish kidney""nourish blood""dispel blood stasis", and improve the endometrium. By means of combination of disease and syndrome, classical prescription addition and subtraction, clinical effective experience, combination of acupuncture and medicine and external treatment of Traditional Chinese Medicine can improve the effect and prognosis of patients with endometrial injury diseases. This article reviews the progress of combined Traditional Chinese and Western Medicine treatment of endometrial injury diseases to provide reference for its clinical treatment.

Objective Human facial morphology is an appearance phenotype with high heritability,high diversity,and complexity.Traditional facial morphological genetic analysis is mostly based on facial landmark measurements,using linear regression for genome-wide association studies,but this method extracts limited facial morphological feature information.This study established an extraction method for multidimensional facial representations and validated the correlation between 473 single-nucleotide polymorphisms(SNPs)previously reported to be significantly associated with facial features and facial representations in the Han Chinese population.Methods After acquiring facial 3D images,3D morphable face models and HR-net network were used to align and quantify the 3D images,obtaining high-density 3D facial point cloud data.After unsupervised clustering of the point cloud,principal component analysis was applied to reduce dimensionality and extract multidimensional morphological phenotypes for each facial region.Based on these multidimensional phenotypes,partial least squares regression(PLSR)and canonical correlation analysis(CCA)were used for genetic association analysis.Results A total of 10 SNPs were validated to be significantly associated with facial morphology in Han Chinese,of which 7 SNPs were validated by the PLSR method,2 SNPs were validated by the CCA method,and 1 SNP was validated by both methods.Conclusion Among the 10 significantly associated SNP sites,9 related facial morphological regions were consistent with previous reports in other populations,indicating that genes affecting complex facial morphology have cross-population effects.

Background:Acute pancreatitis(AP)is a common disease of the digestive system,among which severe acute pancreatitis(SAP)has a high mortality rate.Finding more accurate and convenient methods for early recognition of SAP is one of the major challenges in clinical treatment.Aims:To explore the application value of the controlled attenuation parameter(CAP)of ultrasound elastography in predicting SAP.Methods:A retrospective cohort study was conducted involving 135 AP patients admitted to Jiading Branch of Shanghai General Hospital from February to October 2024.Patients were categorized into non-SAP and SAP groups according to the severity of the disease.Clinical data,local complications,laboratory indicators,and CAP were compared between the two groups.Univariate and multivariate Logistic regression analyses were used to identify independent risk factors for SAP.A SAP prediction model based on CAP was constructed according to the identified risk factors and the minimum Akaike information criterion(AIC).ROC curve and Bootstrap method were used to evaluate the efficacy of the prediction model and conduct internal validation,respectively.Results:There were statistically significant differences between the non-SAP group and SAP group in body mass index(BMI),incidence of hyperlipidemia,etiological composition,incidence of pleural and ascitic fluid,length of hospital stay,incidence of peripancreatic effusion,incidence of pancreatic necrosis,white blood cell count(WBC),D-dimer(D-D)level,blood glucose,triglyceride(TG),C-reactive protein(CRP),neutrophil count,procalcitonin(PCT),interleukin-6(IL-6),free triiodothyronine(FT3),and CAP(all P<0.05).Multivariate Logistic regression analysis showed that pancreatic necrosis(OR=13.39,95%CI:3.10-57.94,P<0.001)and CAP(OR=1.01,95%CI:1.01-1.02,P=0.038)were independent risk factors for SAP.The SAP prediction model based on CAP was formulated as:Logit(P)=-5.884+0.010×CAP+2.839×pancreatic necrosis+0.169×D-D+0.132×blood glucose+0.006×CRP.The model showed an area under the curve(AUC)of 0.834 for predicting SAP,which was superior to CAP alone(P<0.05).Internal validation indicated that the prediction model had high stability and accuracy(C-index=0.808).Conclusions:The prediction model constructed based on CAP has good clinical value for predicting SAP,providing a new perspective and tool for early identification and prognostic assessment of AP.

Endometrial injury diseases are an important factors in female infertility, reduced menstruation, and adverse pregnancy outcomes. Clinical characteristics include intrauterine adhesions, a thin endometrium, and reduced endometrial receptivity. Restoring the morphology of the uterine cavity and promoting endometrial reconstruction are the main goals of treatment. At present, hormone medication and surgery are the major Western medicine treatments. Traditional Chinese Medicine has an advantage in treating endometrial injury and preventing postoperative recurrence. Traditional Chinese Medicine diagnosis focuses on "kidney deficiency" as the primary condition,"blood stasis" as the secondary condition, and combined with "liver depression". Therapeutic strategies aim to "replenish kidney""nourish blood""dispel blood stasis", and improve the endometrium. By means of combination of disease and syndrome, classical prescription addition and subtraction, clinical effective experience, combination of acupuncture and medicine and external treatment of Traditional Chinese Medicine can improve the effect and prognosis of patients with endometrial injury diseases. This article reviews the progress of combined Traditional Chinese and Western Medicine treatment of endometrial injury diseases to provide reference for its clinical treatment.

Based on network pharmacology,molecular docking technology and experimental valida-tion to explore the therapeutic efficacy and mechanism of action of baicalin(BC)on kidney injury caused by Klebsiella pneumoniae(KP)infection.The inhibitory activity of BC against KP was de-termined by in vitro experiments;a mouse kidney injury model was established,and the therapeu-tic effect was preliminarily verified by ophthalmoscopy and pathological histology;three pro-in-flammatory factors,namely,TNF-α,IL-10,and IL-1β,were detected by ELISA;and the cyber-pharmacology technology was utilized by PubChem,TCMSP,STRING,Cytoscape,AutoDocks and other databases and software to construct the PPI network as well as to perform GO function and KEGG enrichment analyses;and molecular docking technology was used to assess the binding ac-tivity of the drugs to the core targets and to speculate on the signaling pathways of the drug action.The results showed that BC had a better inhibitory effect on KP in the in vitro experiments;path-ological histology showed a significant therapeutic effect of BC;compared with the infected group,the content of pro-inflammatory factors TNF-α,IL-10,and IL-1β in the baicalin treatment group were significantly decreased(P≤0.05).Twenty-four core targets and 11 pathways of action were screened by network pharmacology,and BC docked stably with the acquired core targets TP53,PTGS2,MAPK1,MAPK8,TNF,BCL2,and IGF1 molecules,and it was speculated that BC might exert its antibacterial and anti-inflammatory effects through the signaling pathways of PI3K-Akt,MAPK,HIF-1,and NF-kappa B,etc.This study lays the foundation for further research on the mechanism of action of baicalin on renal injury.

Objective:To construct a risk prediction model for Vaginal Intraepithelial Neoplasia Grade 2 or Worse(VaIN 2+)lesions,and to establish a nomogram for individual diagnosis of VaIN 2+and risk stratification,so as to provide guidance for the treatment of vaginal lesions.Methods:A total of 248 women diagnosed with VaIN through colposcopic biopsy at the Center for Gynecologic and Cervical Diseases,First Affiliated Hospital of Nanjing Medical University,from January 2021 to January 2024 were included in this study.Based on the gold standard established by histological and pathological findings,these patients were categorized into a lower VaIN 2 group and a VaIN 2+group.Univariate comparative analysis was performed on the two groups.Multivariate Logis-tic regression analysis was used to determine the risk factors of VaIN 2+and to construct a diagnostic model.The nomogram model was established by using R Studio software.The discrimination,calibration and clinical practical value of the model were evaluated by the area under the receiver operating characteristic(ROC)curve and cali-bration curve.Results:Univariate analysis identified that HPV type,cervical lesion grade,acetowhite change,vagi-nal lesion duration,vaginal lesion location,and cervical lesion duration as influencing factors for diagnosing VaIN 2+(P<0.1).Multivariate binary Logistic regression analysis indicated that HPV16/18 positivity,cervical lesion grade≥CIN 2,thick acetowhite change,vaginal lesion duration≥5 years,and vaginal lesion location at the upper 1/3 of the vagina were independent risk factors for diagnosing VaIN 2+(OR>1,P<0.05),while cervical lesion duration<3 years was a protective factor(OR<1,P<0.05),with acetowhite change having the greatest impact(OR4.54).A regression model was established based on the multivariate binary Logistic regression analysis,with an AUC of 0.813.A nomogram model was constructed and internally validated,yielding a consistency index(C-index)of 0.81.Patients were stratified into risk groups using the X-tile software,with higher total scores indi-cating a greater risk of developing VaIN 2+.Conclusions:The nomogram model constructed in this study can in-dividually predict the risk of VaIN 2+lesions in patients,with high accuracy and clinical practicability.

Objective To investigate the effect of peptidyl arginine deiminase 4(PAD4)on the differentiation of mesenchymal stem cells isolated from oral bones(OMSC)and craniomaxillofacial development.Methods Immunofluorescence was used to detect the ex-pression of PAD4 in the mandibular of mice E13.5 embryo.A peptidyl arginine deiminase 4 knockout(PAD4-KO)mouse model was constructed.Craniomaxillofacial development was investigated by micro-CT.CCK-8 assay and Transwell assay were used to detect the OMSC proliferation ability and migration ability of PAD4-KO and wild type(WT)mouse.ALP staining was used to detect the changes in OMSC osteogenic differentiation ability.The expression of osteogenesis-related genes was detected by immunofluorescence and PCR assay.Results PAD4 was highly expressed in the mandibular tissue of mouse embryos at E13.5.On the cellular level,PAD4 was ex-pressed in the nucleus and mitochondria of OMSC.Compared to the WT mice,micro-CT showed that PAD4-KO mice had retrusive jaw and decreased mineralization.The proliferation and migration ability of OMSC in PAD4-KO mice were decreased.OMSCs lacking PAD4 had significantly decreased ALP staining level,and the expression levels of osteogenesis-related genes were decreased.In addition,it was found that PAD4 might affect OMSC mineralization by regulating Runx2 transcription.Conclusion PAD4 is expressed in the jaw during embryonic development.It might affect the embryonic development by regulating the proliferation and differentiation of OMSC,leading to craniomaxillofacial abnormalities