ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

Objective To investigate the feasibility of the spatiotemporal filtering model in analysis of reported schistosomiasis cases, so as to provide insights into analysis of complicated data pertaining to schistosomiasis control. Methods Demographic and epidemiological data of reported schistosomiasis cases in Anhui Province from 1997 to 2010 were collected from Anhui Provincial Center for Disease Control and Prevention, and the annual prevalence of Schistosoma japonicum human infections was calculated. The meteorological data were captured from meteorological stations in counties (cities, districts) of Anhui Province where schistosomiasis cases were reported from 1997 to 2010 at the National Meteorological Information Center, including monthly average air temperature and precipitation. Meteorological data were interpolated using the inverse-distance weighting method, and the annual average air temperature and annual precipitation were calculated in each county (city, district). The centroid of the county (city, district) where schistosomiasis cases were reported was extracted using the software ArcGIS 10.0, and the Euclidean distance from each centroid to the Yangtze River was calculated as the distance between that county (city, district) and the Yangtze River. The global Moran’s I of the prevalence of S. japonicum human infections in Anhui Province for each year from 1997 to 2010 were calculated to analyze the spatial autocorrelation. A spatial weight matrix was constructed using Rook adjacency, and a first-order temporal weight matrix was built to quantify the relationship between disease changes over time. Subsequently, a spatiotemporal structure matrix was constructed. A negative binomial model was built based on the spatiotemporal structure matrix and data pertaining to reported schistosomiasis cases, and a linear model was created between the residual of the model and candidate set feature vectors to determine the optimal subset composition of the spatiotemporal filter through stepwise regression. Then, a spatio-temporal filtering model was constructed using the negative binomial model. Negative binomial models, Bayesian spatial models, and Bayesian spatiotemporal models were constructed and compared with the spatiotemporal filtering model to validate the performance of the spatiotemporal filtering model, and cross-validation was conducted for each model. The goodness of fit was evaluated using the deviance information criterion (DIC) and Watanabe-Akaike information criterion (WAIC), and the effectiveness of model validation was assessed using mean squared error (MSE), while the accuracy of assessment results was assessed using coefficients and their 95% confidence intervals (CI), and the computational efficiency was assessed based on the running time of the model. The four feature vectors with the largest Moran’s I values were selected to identify regions with autocorrelation through their schematic diagrams to investigate the differences in spatiotemporal patterns of specific regions. Results Of all models created, the spatiotemporal filtering model exhibited the highest goodness of fit (DIC = 3 240.70, WAIC = 3 257.80), the best model validation effectiveness (MSE = 42 617.52), and the runtime was 3.18 s, exhibiting the optimal performance. Across all modeling results, the distance from the Yangtze River showed a negative correlation with the number of reported schistosomiasis cases (coefficient values = −4.93 to −3.78, none of the 95% CIs included 0), and annual average air temperature or average precipitation posed no significant effects on numbers of reported schistosomiasis cases (both of the 95% CIs included 0). Schematic diagrams of feature vectors showed that the transmission of schistosomiasis might be associated with water systems in Anhui Province, and localized clustering patterns were primarily concentrated in the northern and western parts of schistosomiasis-endemic areas in the province. Conclusion The spatiotemporal filtering model is an effective spatiotemporal analysis characterized by simple modeling, user-friendly operation, accurate results and good flexibility, which may serve as an efficient alternative to conventional complex spatiotemporal models for data analysis in schistosomiasis researches.

In recent years,radiation therapy has become a cornerstone in the treatment of head and neck tumors,significantly improving patient survival rates.However,the issue of radiation-induced carotid artery stenosis has garnered increasing attention.Characterized by multiple,long-segment,and unstable lesions,radiation-induced carotid stenosis presents unique challenges that traditional therapeutic approaches struggle to address.This review systematically summarized the pathological features and underlying mechanisms of radiation-induced carotid stenosis,with a focus on the roles of endothelial cells,smooth muscle cells,and vasa vasorum damage.Future research directions and preventive strategies are also discussed.

Both Wnt/β-catenin signaling pathway and NF-κB signaling pathway are highly conservative pathways that regulate a variety of biological processes, and their cross-regulation have attracted attention in many biological and medical research fields. In this review, we summarize the cross-regulation between Wnt/β-catenin signaling pathway and NF-κB signaling pathway and discuss their involvement in the multi-directional differentiation of mesenchymal stem cells.

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [¹⁸F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [¹⁸F]FBTA has a strong STING binding affinity (K_d = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [¹⁸F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG).

Objective:To investigate the efficacy of internal fixation of Pipkin types I and II femoral head fractures through the modified Smith-Petersen (S-P) approach.Methods:A retrospective case control study was conducted to analyze the clinical data of 33 patients with Pipkin types I and II femoral head fractures admitted to Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from June 2015 to September 2019. There were 22 males and 11 females, aged 20-40 years (mean, 29.5 years). There were 15 patients with Pipkin type I fractures and 18 with Pipkin type II fractures. A total of 22 patients were treated using the modified S-P approach via the sartorius and tensor fascia lata space (modified S-P group) and 11 patients were treated using the modified K-L approach via the posterior superior iliac spine and gluteus maximus (modified K-L group). The operation duration, intraoperative blood loss, postoperative drainage volume, length of hospital stay, numeric rating scales (NRS) for pain assessment at postoperative 15 days, bone healing time, Harris hip joint score at postoperative one month, and complication rate were compared between the two groups.Results:All patients were followed up for 1-24 months (mean, 6.5 months). The operation duration, blood loss, drainage rate and length of hospital stay in modified S-P group were better than those in modified K-L group [(71.7±7.3)minutes vs. (112.1±6.7)minutes, (55.9±6.2)ml vs. (99.4±8.7)ml, (91.2±5.9)ml vs. (121.3±7.0)ml, (6.0±1.5)days vs. (10.5±1.6)days] ( P<0.01). There were no significant differences between two groups in terms of NRS, bone healing time and Harris score ( P>0.05). The incidence of complications was similar between the two groups, including femoral head ischemia necrosis, traumatic arthritis, and heterogenous ossification ( P>0.05). Conclusion:For Pipkin types I and II femoral head fractures, the modified modified S-P approach is superior to modified K-L approach in aspects of operative time, intraoperative blood loss, postoperative drainage and length of hospital stay.

Objective: To explore the acute effect of fine particulate matters (PM_2.5), O₃, NO₂ on daily non-accidental mortality, cardiovascular disease mortality and respiratory mortality data in thirteen cities of Jiangsu province. Methods: Daily average concentrations of non-accidental mortality, cardiovascular disease mortality, respiratory mortality data and environmental data were collected from January 1, 2015 to December 31, 2017 in thirteen cities of Jiangsu Province. Daily air quality, mortality and meteorology data were collected from the Information System of Air Pollution and Health Impact Monitoring of Chinese Center for Disease Control and Prevention. We used generalized additive model to evaluate the association between daily concentrations of air pollutants and mortality at single-city level and multi-city level, after adjusting the long-term and seasonal trend, as well as meteorological factors and the effect of "days and weeks" . A multivariate Meta-analysis with random effects was applied to estimate dose-response relationship between air pollutants and mortality. Results: At multi-city level, per interquartile range increase of PM_2.5, O₃, NO₂ was associated with an increase of 1.10% (95%CI: 0.66%, 1.54%), 0.59% (95%CI: 0.18%, 1.00%), 2.00% (95%CI: 1.29%, 2.72%) of daily non-accidental mortality respectively; 1.01% (95%CI: 0.63%, 1.38%), 0.66% (95%CI: 0.02%, 1.30%), 1.62% (95%CI: 1.00%, 2.23%) of daily cardiovascular mortality respectively; 1.09% (95%CI: 0.35%, 1.82%), 0.44% (95%CI: -0.29%, 1.16%), 2.75% (95%CI: 1.42%, 4.08%) of daily respiratory mortality respectively. The air pollutants effect varied across different cities. The strongest effect of PM_2.5 was current day (excess risk (ER)=1.10%, 95%CI: 0.66%, 1.54%)), the strongest effect of O₃ was 2-day lag (ER=1.82%, 95%CI: 0.69%, 2.97%) and the strongest effect of NO₂ was 1-day lag (ER=2.09%, 95%CI: 1.34%, 2.83%) of daily non-accidental mortality respectively. Conclusion The increases of PM_2.5 and NO₂ concentration could result in the increases of daily non-accidental mortality, cardiovascular disease mortality and respiratory mortality. O₃ could result in the increases of daily non-accidental mortality and cardiovascular disease mortality. The acute effects for non-accidental mortality from high to low were NO₂, PM_2.5 and O_3, and the strongest effect of PM_2.5 was current day. O₃ and NO₂ had lagged effects.

OBJECTIVETo prepare nanofibrous membranes of poly (vinyl alcohol)/chitosan (PVA/CS) loaded with varied salvianic acid A sodium (SAS) contents.

METHODSUltrafine fiber mats were prepared with PVA/CS as matrix and SAS as model drug. The structure and morphology of the nanofibrous membranes were characterized by FT-IR and SEM. Drug-loading amount and drug release profiles of these membranes were determined by UV VIS spectra, and the degradation of the membranes was also investigated.

RESULTSAverage diameters of PVA/CS/SAS nanofibers with different SAS contents were 280 ≊390 nm. Drug-loading amount of these nanofibrous membranes was high and exhibited sustained and controlled release behavior for SAS.

CONCLUSIONThe PVA/CS/SAS nanofibrous membrane prepared in this study loads drug uniformly and has remarkably sustained release behavior, which may offer strategies for the research and development of novel topical drug delivery systems.

Objective To investigate the feasibility of adrenal sparing surgery for selected renal cell carcinoma (RCC), since the necessity of routine adrenalectomy during radical nephrectomy for RCC has been challenged in recent years.Methods 178 patients underwent perifascial nephrectomy in a 16-year period. Of these patients, 96 had ipsilateral adrenal gland preserved during nephrectomy and 82 underwent concomitant adrenalectomy. 75 excised adrenal specimens were examined pathologically. Disease specific survival rates were assessed according to the pathological stage of the tumors.Results Of the 75 patients, 53 presented a macroscopically normal adrenal gland without patho- histological changes. The other 22 patients were suspected to have adrenal metastasis intraoperatively, while only 5 of them were confirmed to have adrenal involvement by histopathology. Two patients in the adrenal gland preservation group developed ipsilateral adrenal recurrence and synchronous or metachronous contralateral adrenal metastasis during follow-up, although both were documented to have a normal-appearing adrenal gland intraoperatively. Five patients with adrenal metastasis and 2 patients with adrenal recurrence had large renal tumors. The survival difference among subgroups of patients undergoing adrenalectomy or with adrenal gland left in situ was not statistically significant.Conclusion Adrenal sparing surgery could be done for patients with small renal tumors along with macroscopically normal ipsilateral adrenal glands.