The 95% ethanol extract of Stephania hernandifolia was isolated and purified by column chromatography on silica gel and Sephadex LH-20, RP-18 medium-pressure liquid chromatography, and semi-preparative high performance liquid chromatography. The chemical structures of the compounds were identified by NMR and high-resolution mass spectrometry. Four alkaloids were isolated and identified as(-)-8-oxo-2,3,4,10,11-pentamethoxyberberine(1),(-)-8-oxo-11-hydroxy-2,3,4,10-tetramethoxyberberine(2), N-trans-feruloyl tyramine(3), and N-cis-feruloyl tyramine(4). Compounds 1 and 2 were new protoberberine alkaloids, while compounds 3 and 4 were amide alkaloids. All the four compounds were separated from this plant for the first time. The inhibitory activities of compounds 1, 3, and 4 against α-glycosidase were measured by the enzymatic reaction in vitro with 4-nitrophenyl-α-D-glucopyranoside(PNPG) as the substrate. Compounds 3 and 4 showed inhibitory activities against α-glucosidase, with median inhibition concentration(IC_(50)) values of(7.09±0.42) and(31.25±1.14) μmol·L~(-1), respectively.
Berberine Alkaloids/isolation & purification* ; Stephania/chemistry* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; alpha-Glucosidases/metabolism* ; Chromatography, High Pressure Liquid ; Alkaloids/isolation & purification*

AIM To explore the effects of Hofmeister series ions on encapsulation efficiencies of cinnamaldehyde,paeonol,and ligustilide in inclusion complex of volatile oils from Wenjing Decoction.METHODS The volatile oils were extracted,after which the β-cyclodextrin inclusion complex was prepared,the thermal stability was evaluated,and encapsulation efficiencies and inclusion complex constants of various volatile components in Na2SO4,NaH2PO4,NaCl,NaI,NaSCN solutions were determined.RESULTS The β-cyclodextrin inclusion complex demonstrated good thermal stability within 10 d.After the addtion of Hofmeister series ions,various volatile components displayed increased encapsulation efficiencies and inclusion complex constants,and concentration-dependent manner was observable in the latter.CONCLUSION Hofmeister series ions can affect the binding affinities of volatile components and β-cyclodextrin in volatile oils from Wenjing Decoction,thus regulate their encapsulation efficiencies.

Objective:To evaluate the clinical efficacy of free anterolateral thigh perforator flap (ALTPF) for reconstruction of soft tissue defects in lower extremity in elderly patient.Methods:From February 2018 to August 2024, 24 elderly patients (14 males, 10 females. Age range: 70-89 years, mean age: 73.47 years) with soft tissue defects in lower extremity were treated with free ALTPFs in the Department of Hand Microsurgery, Sichuan Modern Hospital. All patients had comorbidities including chronic pulmonary diseases (10 cases), anaemia in various severity (15 cases), atherosclerosis (9 cases), diabetes mellitus (6 cases), hypertension (5 cases) and great saphenous varicose veins (4 cases). Fourteen patients were admitted to hospital though emergency department due to trauma. Of these patients, 2 underwent emergency flap transfer surgery, 12 had temporary wound coverage with negative pressure wound therapy (NPWT) or bone cement, followed by flap surgery at 3-7 days later. Ten patients with chronic wounds were admitted through outpatient clinic and underwent flap surgery at approximately 7 days after multidisciplinary team consultation and completion of preoperative preparation. A total of 15 patients received blood transfusion: 3 before the surgery, 10 in the surgery and 2 after the surgery. Defect locations were: right calf and ankle (6 cases), right foot (5 cases), left calf and ankle (10 cases) and left foot (3 cases). Defect sizes ranged from 5.0 cm×7.0 cm to 9.0 cm×30.0 cm, with exposure of tendon, bone or internal fixation. The size of ALTPFs ranged from 6.0 cm×8.0 cm to 10.0 cm×40.0 cm. All artery of flaps was end-to-end anastomosed with the recipient artery, and the vein of flaps was anastomosed with the accompanying vein by recipient artery. Donor sites were either closed directly or reconstructed with skin grafts. All patients were included in postoperative follow-up via visit of outpatient clinic or WeChat for evaluation of flap and donor sites.Results:All 24 flaps survived. Two cases presented with venous occlusion after surgery and surgical exploration discovered: 1 patient had a long-segment venous thrombosis in the recipient vein and was treated with great saphenous vein transposition for re-anastomosis; the other had a deep haematoma compressing of the flap, which was removed surgically with haemostasis. Follow-up lasted for 3 to 24 months. All donor sites healed well without local tenderness, leaving only linear or skin graft scars. The flap survived well, without infection, ulceration or necrosis. All ankle function was preserved.Conclusion:Transfer of free ALTPF is a valuable technique for treatment of soft tissue defects in lower extremity in elderly patients. Despite higher risks, satisfactory outcome can be achieved with thorough preoperative evaluation and surgical intervention, especially when the condition of a patient is stable, an early ambulation for functional recovery should be started.

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.

Objective:To identify the factors influencing the diagnostic accuracy of endoscopic ultrasonography (EUS) for colorectal submucosal tumors (SMT).Methods:A retrospective analysis was conducted on 330 colorectal SMT lesions (from 323 patients) diagnosed by EUS at Shenzhen Hospital of Southern Medical University from December 2015 to October 2023. Pathological diagnosis were confirmed through endoscopic resection, EUS-guided fine needle aspiration (EUS-FNA) or surgical resection. Diagnostic accuracy was calculated for each type of colorectal SMT. Univariate and multivariate logistic regression analysis were performed to identify factors affecting EUS diagnostic accuracy.Results:The overall diagnostic accuracy of EUS for colorectal SMT was 73.6% (243/330). Among 19 SMT subtypes enrolled, neuroendocrine neoplasms (51.2%, 169/330) and lipomas (15.5%, 51/330) were most prevalent, while 17 rare subtypes each accounted for <6%. Seven rare SMT (mucosal chronic inflammation, colorectal schwannoma, xanthogranulomatous inflammation, capillary hemangioma, colonic xanthoma, lymphadenoid complex, and angiomyolipoma) showed 0% diagnostic accuracy. Seven other subtypes (granular cell tumor, leiomyoma, rectal tonsil, intestinal schistosomiasis, fibrous tissue hyperplasia, gastrointestinal stromal tumor, and lymphangioma) showed accuracy <30%, whereas five subtypes (cyst, bowel endometriosis, neuroendocrine neoplasm, lipoma, and pneumatosis cystoides intestinalis) achieved >60% accuracy. Multivariate logistic regression analysis confirmed that the lesion location (left colon VS rectum: OR=0.06, 95% CI: 0.02-0.17, P<0.001; right colon VS rectum: OR=0.04, 95% CI: 0.01-0.13, P<0.001; ileocecal valve VS rectum: OR=0.09, 95% CI: 0.02-0.42, P=0.002); echogenicity (anechoic VS hypoechoic: OR=6.26, 95% CI: 1.31-29.97, P=0.022; hyperechoic VS hypoechoic: OR=13.39, 95% CI: 4.16-43.09, P<0.001) and ultrasonic layer (layer 4 VS layer 3: OR=0.22, 95% CI: 0.06-0.81, P=0.023) were independent influencing factors of EUS diagnostic accuracy for colorectal SMT. Conclusion:Neuroendocrine neoplasms and lipomas represent the most common colorectal SMT, whereas rare and uncommon SMT exhibit low EUS diagnostic accuracy. Lesion location, echogenicity, and ultrasonic layer significantly influence EUS diagnostic accuracy for colorectal SMT.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Objective To identify potential drug target genes associated with idiopathic pulmonary fibrosis(IPF)and predict therapeutic candidates using a two-sample Mendelian randomization(MR)approach across the druggable genome.Methods Druggable genome data from the DGIdb database and Finan were integrated to identify overlapping genes.A two-sample MR analysis was performed to infer causal relationships between genes and IPF.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),were conducted to explore biological pathways.Drug-target interactions were predicted via DSigDB database screening,followed by molecular docking simulations to evaluate binding affinities.Results Among the 2588 overlapping druggable genes,thirty exhibited significant causal associations with IPF(P＜0.05).Four hub genes(NOD2,LATS2,LTA,and TCF7L2)were enriched in IPF-related pathways,notably Hippo and TNF signaling.Six potential therapeutics were identified:oxyphenbutazone,moexipril,α-galactosylceramide,GSK429286A,CGP74514A,and JW-7-24-1.Molecular docking confirmed strong binding affinities between these drugs and their targets.Conclusion This study has identified thirty druggable gene targets and six candidate drugs for IPF.The enrichment of hub genes in key pathways and validated drug-target interactions provide insights into IPF therapies.

Objective To investigate serum exosomal miRNA spectrum in patients with gestational diabetes mellitus(GDM)and eval-uate its clinical value in the diagnosis of GDM complicated with premature delivery.Methods Serum samples of pregnant women with GDM registered and delivered in our hospital were collected and divided into the premature delivery group and term labor group based on pregnancy outcomes,with 22 cases in each group.Serum exosomal miRNAs were sequenced,and the differentially expressed miRNAs were further verified by fluorescence quantitative PCR.The receiver operating characteristic(ROC)curve was drew according to the verified expression level of miRNAs,and the value of exosomal miRNAs in the diagnosis of GDM complicated with premature de-livery was analyzed.The potential functions of candidate miRNAs were predicted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Results A total of 94 differentially expressed miRNAs,including 50 up-regulated and 44 down-regulated,were identified in the premature delivery group and term labor group.The verification results of fluorescence quantitative PCR showed that 7 miRNAs had significant difference between the two groups(P<0.05).Moreover,the expression trend was consistent with the sequencing results.The analysis results of the ROC curve showed that the seven miRNAs had good diagnostic efficacy for GDM combined with premature delivery.The areas under the ROC curve(AUCROC)of hsa-miR-16-5p,hsa-miR-25-3p,hsa-miR-30b-5p,and hsa-miR-92a-3p were all more than 0.7.Their sensitivity and specificity were 0.375 and 1.000,0.563 and 0.941,0.563 and 0.824,and 0.765 and 0.647,respectively.The binary logistic regression analysis showed that the AUCROC of the combination of hsa-miR-16-5p,hsa-miR-25-3p,hsa-miR-30b-5p,and hsa-miR-92a-3p for the diagnosis of GDM complicated with premature delivery increased to 0.982,and that its sensi-tivity and specificity were both more than 0.850.These candidate miRNAs were related to the ubiquitin-mediated proteolysis pathway,actin cytoskeleton regulatory pathway,mTOR signaling pathway,and P53 signaling pathway.Conclusion Serum exosomal miRNAs in GDM patients complicated with premature delivery have significant difference,which may be served as potential diagnostic markers.

Objective:To establish a prediction model for larger for gestational age(LGA)infants in pregnant women with gestational diabetes mellitus(GDM)in order to improve pregnancy outcomes.Methods:A retro-spective analysis was performed on the clinical data of 338 pregnant women with GDM who underwent routine prenatal examinations and were hospitalized for delivery in the First Affiliated Hospital of Nanjing Medical Universi-ty from January 1,2018 to December 31,2023.Pregnant women with complete HbAlc data during pregnancy were divided into a training set of 241 cases and a validation set of 97 cases.Lasso and Logistic regression analysis and variable screening combined with previous clinical experience were used to construct a nomogram model,and its degree of differentiation and calibration were evaluated.Result:①By Lasso regression analysis,age,family histo-ry of type 2 diabetes,body mass index(BMI),gestational weight gain(GWG),fasting blood glucose(FBG),postprandial 1-hour blood glucose(1h PBG),HbAlc,free triiodothyronine(FT3),free thyroxine(FT4)and insulin treatment were important predictors of LGA.②Multivariate Logistic regression analysis showed that GWG and HbAlc were independent risk factors for LGA in pregnant women with GDM(OR＞1,P＜0.05).③Combined with Lasso and Logistic regression analysis,previous literature reports and clinical experience,BMI,GWG,FBG,1h PBG,HbAlc and FT3 were selected as independent variables,and LGA as dependent variable.A nomogram pre-diction model was constructed in the training set,and the C-index of 0.71.ROC curve analysis showed that the AUC values of the training set and the validation set were 0.709 and 0.700,respectively,and the discriminative a-bility of the model was acceptable.The calibration curve of the model was close to the ideal curve,and the clinical decision curve suggested that the model showed a positive net benefit at the threshold of 10％to 50％.Conclu-sion:The predictive model has certain value in predicting the occurrence of LGA in pregnant women with GDM,and provides help for early diagnosis,treatment and clinical intervention of GDM and its complications,in order to improve perinatal and long-term adverse outcomes.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.