Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective To evaluate the performance of a blood nucleic acid testing kit,construct a consistency assess-ment system,and analyze the influencing factors of the test results.Methods A total of 18 644 samples of voluntary blood donors in our center were collected,and 189 double positive samples of hepatitis B surface antigen(HBsAg)by ELISA were eliminated,and the remaining 18 455 samples were tested for HBV DNA in parallel with the test reagent and the control rea-gent(Roche Company).Samples with inconsistent results were confirmed with third-party reagents(Grifols Company,with the sensitivity of HBV DNA,HCV RNA and HIV RNA of 4.5 IU/mL,2.4 IU/mL and 17.3 IU/mL by single reagent,which were significantly better than other reagents),and the consistency between the two methods was compared.Results No HCV RNA or HIV RNA positive samples were detected in this study.Among the 18 455 samples in initial test,12 were pos-itive with consistent results,18 378 were negative with consistent results,and 65 were with inconsistent results between the test reagent and the control reagent,with positive concordance rate,negative concordance rate and concordance rate of the two reagents at 85.17％,99.66％and 99.65％,respectively.In order to further clarify the infection of 65 inconsistent sam-ples,five qualitative tests of hepatitis B and single NAT were conducted to comprehensively evaluate the infection.The re-sults showed that there were 60 positive samples with consistent results,18 371 negative samples with consistent results,and 24 samples with inconsistent results between the test reagent and the control reagent,with positive concordance rate,nega-tive concordance rate and the concordance rate for the two reagents at 86.96％,99.92％and 99.87％,respectively.The Kappa value was 0.83,and the Youden index was 0.40.The ROC curve was plotted with the false-positive rate(1-specifici-ty)as the horizontal coordinate and the true-positive rate(sensitivity)as the vertical coordinate,and the area under the ROC curve was 0.705.189 double-positive samples were selected for conformance testing,and the Ct values of the test rea-gent and the control reagent were analyzed and fitted linearly,with correlation coefficient r=0.972.A Bland-Altman model was constructed with the mean value of the logarithm of the quantitative values of the test reagent and the control reagent as the horizontal coordinate and the difference as the vertical coordinate,and 96.30％of the difference values of the test rea-gents were within the confidence interval.Conclusion The construction of the consistency evaluation system showed that the test reagent has similar detection efficiency with the control reagent,and is suitable for HBV DNA routine screening,which can effectively ensure the safety and effectiveness of blood screening.

Objective:To explore the relationship between normal serum creatinine(Scr) level and diabetic kidney disease(DKD) in patients with type 2 diabetes mellitus(T2DM).Methods:This was a prospective cohort study. Patients with yet not DKD who were regularly followed up at six centers of Li′s United Clinic in Taiwan, China from January 1, 2002 to December 31, 2018 were selected. At baseline, clinic information and lab tests were collected. According to whether the patients developed DKD during the follow-up period, they were divided into DKD group and non-DKD(NDKD) group. The exposure factor was the Scr(μmol/L) value, and it was used as a categorical variable. According to the quartiles of Scr, they were divided into 4 groups: Q1 group(Scr<57.68 μmol/L), Q2 group(57.68 μmol/L≤Scr<68.51 μmol/L), Q3 group(68.51 μmol/L≤Scr<80.44 μmol/L) and Q4 group(Scr≥80.44 μmol/L). The Cox regression model was used to explore the relationship between Scr level and the incidence of DKD. Receiver operating characteristic(ROC) curve was used to analyze the predictive effect of normal level Scr on DKD. Results:A total of 2 202 T2DM patients without DKD at baseline were included. After a follow-up period of(5.2±2.17) years, there were 966 patients in the DKD group and 1 236 patients in the NDKD group. Compared with the NDKD group, the DKD group had older age, longer duration of diabetes, higher BMI, SBP, DBP, LDL-C, Scr, and UACR(all P<0.05). Cox regression analysis results showed that compared with the Q1 group as the reference, the risk of developing DKD in the Q2, Q3, and Q4 groups after adjusting for confounding factors was 1.394, 1.688, and 2.821 times higher, respectively(all P<0.05). ROC curve analysis results showed that the area under the curve(AUC) for predicting DKD occurrence using normal serum creatinine level was 0.70(95% CI 0.678-0.722), with an optimal cutoff value of 74.27 μmol/L, sensitivity of 0.54, and specificity of 0.76. The cumulative risk plot showed that after adjusting for confounding factors, patients in the Q4 group had a higher cumulative risk of developing DKD compared to the Q1, Q2, and Q3 groups(all P<0.05). Conclusion:Scr is an independent risk factor for developing DKD in patients with T2DM. The higher the Scr level, the greater the risk, especially when Scr is greater than 74.27 μmol/L.

Objective:To analyze the researches on nutrition for premature infants and steer future research directions.Methods:The Web of Science core collection was employed as the primary source to conduct a comprehensive search and retrieve relevant literature on nutrition for premature infants published up from 1975 to December 2023. A visualized analysis was conducted using CiteSpace.Results:After screening, a total of 2 661 publications were included. A rising trend was seen in the amount of publications. Countries with the most publications were the United States, the United Kingdom, and Italy, with the leading institutions of Baylor College of Medicine and the University of Copenhagen. Shanghai Jiao Tong University was the institution that published the most in China. Key topics that were studied frequently encompassed parenteral nutrition, breast milk utilization and necrotizing enterocolitis. Cluster analysis of keywords identified 18 representative cluster labels, revealing the research focuses on parenteral nutrition, enteral nutrition, necrotizing enterocolitis and feeding intolerance in premature infants.Conclusion:The researches on nutrition for premature infants are on the rise, and the nutritional support regimen, how to reduce complications, and nutritional care are the hot topics of future researches on nutrition for premature infants.

Evidence mapping was performed to review the clinical trials and systematic reviews about the treatment of hyperlipidemia with Chinese patent medicines in recent ten years. A total of 387 clinical studies and 18 systematic reviews/Meta-analysis involving 45 Chinese patent medicines commonly used in the treatment of hyperlipidemia in recent ten years were retrieved from Chinese and English academic publication databases. The article information was extracted by reading the abstract and full text, and the evidence of publication trend, combined medication, intervention course, complications, and outcome indicators was sorted out. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of some randomized controlled trial(RCT), and the research results were presented by figures combined with tables. The Chinese patent medicines mostly mentioned included Xuezhikang Capsules, Yindan Xinnaotong Capsules, Hedan Tablets, Pushen Capsules, and Compound Danshen Dropping Pills. The outcome indicators included blood lipid levels(total cholesterol, low-density lipoprotein, etc.), clinical efficacy(markedly effective, effective, and ineffective), adverse reactions(mainly including gastrointestinal reactions), hemorheological indicators, and liver and kidney functions. The available studies generally had small sample sizes, short period, and insufficient attention to traditional Chinese medicine(TCM) syndromes. The RCT and systematic reviews/Meta-analysis generally had low quality, and thus the results had low reliability. Nevertheless, the studies demonstrated a heightened focus on adverse reactions, diverse combined intervention measures, and varied options for addressing different complications. It is recommended that the clinical research on Chinese patent medicines for hyperlipidemia should strive to improve research quality, standardize research protocols, and devote greater attention to TCM syndromes, thereby enhancing the influence and effectiveness of these medicines.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Hyperlipidemias/drug therapy* ; Nonprescription Drugs/therapeutic use* ; Randomized Controlled Trials as Topic

OBJECTIVES: To investigate the clinical application of endoscopic esophageal dilation in the treatment of corrosive esophageal strictures in children. METHODS: A retrospective analysis was performed on the clinical data of 15 children with corrosive esophageal strictures who underwent endoscopic esophageal dilation in Children's Hospital, Zhejiang University School of Medicine. The clinical features, treatment modality of endoscopic esophageal dilation, number of dilations, complications, and prognosis were reviewed. RESULTS: A total of 96 esophageal dilations were performed in the 15 children with corrosive esophageal strictures, with a median of 6 dilations per child. Among them, 9 children (60%) underwent 6 or more dilations. The children with a stricture length of >3 cm had a significantly higher number of dilations than those with a stricture length of ≤3 cm (P<0.05). The children with strictures in a single segment had a significantly better treatment outcome than those with strictures in multiple segments (P=0.005). No complication was observed during all sessions of dilation. The overall effective rate (including significant improvement and improvement) of endoscopic esophageal dilation treatment was 87%, with 2 cases of failure. CONCLUSIONS Endoscopic esophageal dilation is an effective and relatively safe treatment method for corrosive esophageal strictures in children, and children with strictures in a single segment tend to have a better treatment outcome than those with strictures in multiple segments.
Child ; Humans ; Esophageal Stenosis/therapy* ; Constriction, Pathologic/complications* ; Dilatation/methods* ; Caustics ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R. METHODS: Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label. RESULTS: The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results. CONCLUSIONS SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.
Animals ; Humans ; Nasopharyngeal Carcinoma/genetics* ; Epithelial-Mesenchymal Transition ; Zebrafish ; Cell Proliferation ; Cell Line, Tumor ; Nasopharyngeal Neoplasms/radiotherapy* ; Cell Movement ; Gene Expression Regulation, Neoplastic

Background As one of the common tools for job burnout assessment, Maslach Burnout Inventory-General Survey (MBI-GS), its reliability and validity across different populations in China have not been examined yet. Objective To evaluate the reliability and validity of General Burnout Scale (GBS) by multiple occupational groups through the translation and preliminary test of MBI-GS. Methods Based on the Special Project of Occupational Hazards in Key Populations led by the Institute of Occupational Health and Poison Control, China CDC, key occupational groups in five typical industries were selected by multi-stage stratified cluster sampling, including teachers, firefighters, manufacturing workers, medical staff, and traffic police. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of GBS by single-factor, two-factor, and three-factor structure models. The model fitness was assessed by ratio of the chi-square statistic to the respective degrees of freedom (χ²/ν), root mean square error of approximation (RMSEA), goodness-of-fit index (GFI), comparative fit index (CFI), and parsimony-adjusted non-normed fit index (PNFI). Spearman correlation analysis was used to calculate the criterion validity of GBS with occupational stress, depressive symptoms, and sleep disorders. Cronbach's α coefficient and composite reliability (CR) coefficient were used to evaluate the internal consistency reliability of GBS. Results A total of 3485 subjects were surveyed in this study, 3375 valid questionnaires were recovered with a valid response rate of 96.84%. The results of CFA showed that in the adjusted three-factor structure model of GBS (exhaustion, cynicism, and professional efficacy), the χ²/ν < 4, the RMSEA ranged from 0.032 to 0.069, the GFI > 0.90, the CFI > 0.90, and the PNFI > 0.70, which illustrated a good fitness than that of the single- or the two-factor structure models in different occupational groups. The Spearman correlation analysis results showed that occupational stress, depressive symptoms, and sleep disorders were positively correlated with exhaustion and cynicism dimensions, and negatively correlated with professional efficacy dimension of the GBS, with the \begin{document}$ \left| r \right| $\end{document} ranging from 0.139 to 0.662 (P<0.05) in overall subjects. For traffic police and firefighters, professional efficacy was not correlated with depressive symptoms or sleep disorders (P>0.05). The Cronbach's α coefficients ranged from 0.819 to 0.899, and the CR values ranged from 0.941 to 0.978 in different occupational groups. Conclusion The GBS shows high reliability and validity, as well as good application effects in different occupational groups.

Objective:To quantitatively evaluate the stiffness of pancreatic parenchyma and lesions by virtual touch tissue imaging and quantification (VTIQ) technique, and to investigate the potential usefulness of ultrasound shear wave elastography (SWE) in the prediction of clinically relevant post-operative pancreatic fistula (CR-POPF) after pancreatectomy.Methods:Patients who scheduled to receive pancreatectomy were prospectively enrolled in Zhongshan Hospital, Fudan University from March 2021 to December 2021. VTIQ assessment was applied to patients within one week before the scheduled surgery to make quantitative SWE evaluation of target tissue. The SWV values of body part pancreatic parenchyma and lesions were measured and recorded. The palpation stiffness of pancreas was qualitatively evaluated during the operation by the surgeon.CR-POPF was diagnosed according to 2016 International Study Group of Pancreatic Fistula (ISGPF) standard.Grade B/C pancreatic fistula was defined as CR-POPF positive. Recognized peri-operative risk factors of CR-POPF were analyzed. ROC curve analysis was used to evaluate the diagnostic efficacy of SWV value in predicting CR-POPF.Results:A total of 72 patients were finally enrolled in this study, including 47 (65.3%, 47/72) patients who received pancreaticoduodenectomy (PD) and 25 (34.7%, 25/72) patients who underwent distal pancreatectomy. CR-POPF occurred in 22 (30.6%, 22/72) patients after pancreatectomy. The SWV value of body part pancreatic parenchyma was significant lower in CR-POPF positive group than in CR-POPF negative group ( P<0.001). There was no significant difference in lesion SWV value between CR-POPF positive and negative groups ( P=0.664). Besides, the palpation stiffness was no difference between the two groups ( P=0.689). Taking SWV value of pancreatic parenchyma >1.16 m/s as a cut-off value for predicting CR-POPF, the area under the ROC curve (AUROC) was 0.816 with 0.760 of sensitivity, 0.634 of specificity, 67.5% of positive predictive value and 72.5% of negative predictive value, respectively. Conclusions:The VTIQ method may improve the objectivity and accuracy of CR-POPF prediction via pre-operative, non-invasive and quantitative evaluation of pancreatic stiffness, which has potential value in clinical applications.