OBJECTIVE To investigate the mechanism by which Shenfukang capsule （SFK） ameliorates renal interstitial fibrosis （RIF） by regulating macrophage-fibroblast crosstalk via the signal transducer and activator of transcription 3 （STAT3）/Yes-associated protein （YAP） pathway. METHODS RAW264.7 macrophages were induced to polarize with transforming growth factor-β 1 （TGF-β 1 ）. Subsequently， a non-contact co-culture system of macrophages with renal fibroblasts NRK-49F， as well as a non-contact co-culture system of macrophages with YAP-knockdown renal fibroblasts， were established. Cells were treated with low， medium， and high concentrations （4， 8， 16 μg/mL） of SFK， as well as a STAT3 inhibitor （STAT3-I，1.64 μg/mL） and losartan potassium tablets （positive control， 0.28 μg/mL）， for 48 h. After intervention， the protein and mRNA expression levels of CD86， CD163， and STAT3 in macrophages， as well as CD86， F4/80， and STAT3 mRNA， were detected. In co-cultured renal fibroblasts， the protein and mRNA expression levels of α -smooth muscle actin （ α -SMA）， Vimentin， collagen type Ⅰ （Col-Ⅰ）， matrix metalloproteinase-1 （MMP-1）， and YAP were detected. In co-cultured YAP-knockdown renal fibroblasts， the protein and mRNA expression levels of α -SMA， Vimentin， and MMP-1 were also detected. RESULTS Following TGF-β 1 induction， the protein expression levels of CD86， CD163， and STAT3， as well as the mRNA expression levels of CD86， F4/80， and STAT3 in macrophages were significantly increased （ P ＜0.05）. The conditioned medium from polarized macrophages activated renal fibroblasts， as evidenced by significantly increased protein and mRNA expression levels of α -SMA， Vimentin， Col-Ⅰ， and YAP， and significantly decreased protein and mRNA expression levels of MMP-1 in renal fibroblasts （ P ＜0.05）. Treatment with SFK and STAT3-I reversed the changes in the above indicators， with the medium concentration SFK group showing stronge r effects on some indicators than the low and high concentration groups. In the non-contact co-culture experiment of macrophages and YAP-knockdown renal fibroblasts， there were no statistically significant differences in the protein and mRNA expression of α-SMA， Vimentin， and MMP-1 among the groups. CONCLUSIONS SFK can inhibit macrophage-renal fibroblast crosstalk by blocking the STAT3/YAP pathway， thereby delaying the progression of RIF.

Ductular reaction （DR） refers to the adaptive pathological changes that occur after hepatobiliary injury， and it is essentially a repair response involving the proliferation， fibrosis， and inflammation of biliary epithelial cell （BEC）. With the understanding of the biological function of BEC， the potential value of DR in disease prognosis and treatment has gradually become a research hotspot. This article systematically reviews the molecular mechanism of DR， its potential as a therapeutic target， and future development directions， as well as novel therapies suggested by targeting these molecular mechanisms， in order to provide a new direction for overcoming current bottlenecks in the treatment of bile duct diseases.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

[摘 要] 目的：探究重楼皂苷Ⅱ（PPⅡ）抑制甲状腺癌（TC）恶性生物学行为的分子机制。方法：常规培养甲状腺癌细胞TPC1，实验分为sh-NC、sh-可溶性半乳糖凝集素3（sh-LGALS3）、OE-NC、OE-LGALS3和 OE-LGALS3 + PPⅡ组，用转染试剂将应用质粒转染至各组TPC1细胞中。qPCR法检测TPC1细胞中LGALS3 mRNA的表达，WB法检测各组TPC1细胞中LGALS3、PI3K/AKT信号通路相关蛋白的表达，CCK-8法、Transwell实验、划痕愈合实验和流式细胞术分别检测各组TPC1细胞增殖、迁移和侵袭能力，以及细胞凋亡情况。结果：PPⅡ抑制TPC1细胞的增殖、迁移和侵袭，并诱导其凋亡（均P < 0.000 1）。数据库数据分析显示LGALS3在甲状腺癌组织中高表达（P < 0.001）且是PPⅡ的靶基因。LGALS1在TPC1细胞中呈高表达（P < 0.000 1），敲减LGALS3抑制TPC1细胞的恶性生物学行为，并促进其凋亡（均P < 0.000 1），PPⅡ通过抑制LGALS3 mRNA和蛋白的表达（P < 0.01或P < 0.001）从而抑制TPC1细胞的恶性生物学行为（P < 0.01或P < 0.000 1），PPⅡ抑制LGALS3表达抑制PI3K/AKT信号通路的激活水平（P <0.001或P <0.000 1），LGALS3通过PI3K/AKT信号通路促进TPC1细胞的恶性生物行为（P < 0.000 1）。结论：PPⅡ通过抑制TPC1细胞中LGALS3的表达，缓解PI3K/AKT信号通路的过度激活从而发挥抑癌作用。

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

BackgroundCurrent studies on the relationship between depressive symptoms and the risks of stroke and all-cause mortality mostly focus on the elderly population or high-risk groups with chronic diseases. The long-term impact of depressive symptoms in young and middle-aged people on the risks of stroke and all-cause mortality still lacks systematic assessment， and the relevant evidence is insufficient. ObjectiveTo explore the association between depressive symptoms and the risks of stroke and all-cause mortality in young and middle-aged adults， thereby expanding the risk evidence in this age group and providing epidemiological basis for early identification of high-risk individuals and the development of targeted intervention strategies. MethodsBased on data from the National Health and Nutrition Examination Survey （NHANES） database （2009–2018）， a total of 14 947 young and middle-aged respondents aged 18 to 64 were included as the research subjects. Logistic regression and restricted cubic spline （RCS） models were employed to examine the association between depressive symptoms and stroke. Cox proportional hazards model， RCS model， and Kaplan-Meier （K-M） survival curves were used to clarify the relationship between depressive symptoms and all-cause mortality risk. To verify the robustness of main findings， sensitivity analysis was conducted stratified by gender， hypertension， diabetes， hyperlipidemia， body mass index （BMI）， and age. ResultsLogistic regression analysis revealed that compared with the non-depressed group， the risk of stroke in the mild depression group increased by 53.50% （OR=1.535， 95% CI： 1.147–2.053）， while the moderate-to-severe depression group showed the highest risk with a 132.90% increase （OR=2.329， 95% CI： 1.733–3.129）. RCS analysis indicated an approximately linear dose-response relationship between PHQ-9 score and the risk of stroke （P_{for non-linearity}=0.089）， with stroke risk increasing as PHQ-9 scores rose. As the PHQ-9 score increased， the risk of stroke also showed an upward trend. Cox regression analysis demonstrated that compared with the non-depressed group， the risk of all-cause mortality in the mild depression group increased by 48.80% （HR=1.488， 95% CI： 1.164–1.902）， and the moderate-to-severe depression group had a 70.60% increased risk （HR=1.706， 95% CI： 1.310–2.221）. RCS analysis showed a linear dose-response relationship between PHQ-9 scores and all-cause mortality risk （P_{for non-linearity}=0.440）. K-M curves indicated that as the severity of depressive symptoms increases， the risk of all-cause mortality gradually rises （P<0.05）. Sensitivity analysis confirmed that the associations between depression symptoms and risks of stroke and all-cause mortality were not modified by gender， hypertension， diabetes， hyperlipidemia， BMI， or age， demonstrating robust findings. ConclusionAmong the young and middle-aged population， both mild and moderate-to-severe depression were associated with increased risks of stroke and all-cause mortality， with the moderate-to-severe depression group showed more pronounced risk elevations. A positive dose-response relationship was observed between depressive symptoms and these risks.

Objective To investigate the safety, economic benefits and psychological effects of day breast conserving surgery for breast cancer. Methods The demographic data and clinical data of breast cancer patients undergoing day (day surgery group) and ward (ward surgery group) breast conserving surgeries in West China Hospital of Sichuan University from March 2020 to June 2021 were retrospectively collected; the demographic data, clinical data, medical and related transportation costs, and preoperative and postoperative BREAST-Q scores of breast cancer patients undergoing day (day surgery group) and ward (ward surgery group) breast conserving surgery in West China Hospital of Sichuan University from June 2021 to June 2022 were prospectively collected. The safety, economic benefit, and psychological satisfaction of day surgery was analyzed. Results A total of 42 women with breast cancer were included in the retrospective study and 39 women with breast cancer were included in the prospective study. In both prospective and retrospective studies, the mean age of patients in both groups were <50 years. There were only statistical differences between the two groups in the aspects of hypertension (P=0.022), neoadjuvant chemotherapy (P=0.037) and postoperative pathological estrogen receptor (P=0.033) in the prospective study. In postoperative complications, there were no statistical differences in the surgical-related complications or anesthesia-related complications between the two groups in either the prospective study or the retrospective study (P>0.05). In terms of the overall cost, we found that the day surgery group was more economical than the ward surgery group in the prospective study (P=0.002). There were no statistical differences in postoperative psychosocical well-being, sexual well-being, satisfaction with breasts or chest condition between the two groups (P>0.05). Conclusion It is safe and reliable to carry out breast conserving surgery in day surgery center under strict management standards, which can save medical costs and will not cause great psychological burden to patients.

Objective:To investigate the predictive value of computed tomography(CT) based radiomics model for the prognosis of patients with pancreatic ductal adenocarcinoma(PDAC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 206 PDAC patients who were admitted to Zhongshan Hospital of Fudan University from August 2018 to December 2020 were collected. There were 115 males and 91 females, aged (64±9)years. All 206 pati-ents underwent enhanced CT examination. Based on radom number table, the 206 patients were randomly divided into a training set of 165 cases and a validation set of 41 cases with a ratio of 4∶1. The training set was used to construct the prediction model, and the test set was used to validate the performance of the prediction model. Observation indicators: (1) follow-up; (2) analysis of prognostic factors of PDAC patients in the training set; (3) construction and evaluation of prediction model for prognosis of PDAC patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Wilcoxon W test. Comparison of count data between groups was conducted using the chi-square test or corrected chi-square test. The Kaplan-Meier method was used to calculate the survival rate and Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX regression model. The PyCharm software was used for the least absolute shrinkage and selection operator method (LASSO)-COX regression analysis. The receiver operating characteristic curve was plotted to evaluate the performance of radiomics model. Results:(1)Follow-up. Of the 206 patients,205 cases were followed up for 17.1(range, 12.0?40.1)months. The postoperative 1-, 2-, 3-year survival rates were 80.10%, 29.61% and 4.85%. (2) Analysis of prognostic factors for PDAC patients in the training dataset. Results of multivariate analysis showed that pathological N stage was an independent influencing factor for prognosis of PDAC patients in the training set ( hazard ratio=1.476, 95% confidence interval as 1.054?2.067, P<0.05). (3) Construction and evaluation of prediction model for prognosis of PDAC patients. A total of 1 595 radiomics features were finally extracted from the 206 patients. By intra-group feature selection and dimensionality reduction using LASSO-COX regression model, 10 radiomics features were obtained. Combined with 10 radiomics features and 11 clinical features, using the LASSO-COX regression analysis, 15 features were finally extracted to construct the CT based radiomics model for predicting prognosis of PDAC. The areas under receiver operating characteristic curve of the prediction model in predicting 2-year and 3-year overall survival rates of PDAC patients in the training set were 0.834 (95% confidence interval as 0.777?0.891) and 0.883 (95% confidence interval as 0.834?0.932), respectively. The area under curve of the prediction model for patients in the validation set was 0.606 (95% confidence interval as 0.456?0.756) and 0.625 (95% confidence interval as 0.477?0.773). Conclusion:The prediction model constructed on CT based radiomics features and clinical features for predicting the prognosis of PDAC patients shows a promising prediction efficiency.

Objective To investigate the potential mechanism of atorvastatin in treating chronic subdural hematoma(CSDH)through network pharmacology and experimental validation,thereby providing theoretical foundation and experimental evidence for further basic and clinical research.Methods The target genes of atorvastatin and CSDH-related genes were identified through network databases including chEMBL,NCBI PubChem Compound,SwissTargetPrediction,GeneCards,and DisGeNET.Potential target genes of atorvastatin for CSDH treatment were screened using Venn diagrams,followed by enrichment analysis performed with R software.Protein-protein interaction(PPI)analysis was conducted using the STRING database,and molecular docking was employed to verify the binding capability between atorvastatin and the proteins encoded by the target genes.An endothelial cell inflammation model was established to assess the effects of atorvastatin on the expression and secretion of inflammation-related genes using Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and enzyme-linked immunosorbent assay(ELISA).The impact of atorvastatin on endothelial barrier function in the inflammation model was evaluated using the FITC-Dextran permeability assay.Results A total of 19 potential target genes of atorvastatin for CSDH treatment were identified.Enrichment analysis indicated that these genes are primarily involved in the regulation of inflammation,angiogenesis,and coagulation/fibrinolysis processes.Based on the PPI analysis,five key target genes-matrix metalloproteinase 2(MMP-2),matrix metalloproteinase 9(MMP-9),interleukin-6(IL-6),C-X-C motif chemokine ligand 8/interleukin 8(CXCL-8/IL-8),and serpin family E member 1(SERPINE-1)—were selected for molecular docking,which revealed favorable binding interactions between atorvastatin and these proteins.In the endothelial cell inflammation model,atorvastatin suppressed the expression and secretion of the aforementioned genes as well as inflammatory markers such as intercellular adhesion molecule 1(ICAM-1)and vascular cell adhesion molecule 1(VCAM-1)(IL-6:F=64.526,P＜0.001;CXCL-8/IL-8:F=37.779,P＜0.001;ICAM-1:F=86.253,P＜0.001;VCAM-1:F=39.631,P＜0.001;MMP-2:F=264.413,P＜0.001;MMP-9:F=86.675,P＜0.001;SERPINE-1:F=71.180,P＜0.001).Furthermore,atorvastatin alleviated endothelial barrier dysfunction caused by inflammation(F=343.890,P＜0.001).Conclusion Atorvastatin may exert therapeutic effects on CSDH by inhibiting inflammatory responses.