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.

Chronic heart failure is the terminal stage of various cardiovascular diseases， and cardiomyocyte apoptosis is the turning point of decompensation. Studies have shown that traditional Chinese medicine （TCM） could regulate apoptosis-related signaling pathways and factors and inhibit or up-regulate the expression of apoptosis-related proteins. Thus， TCM can reduce cardiomyocyte apoptosis， protect the myocardial tissue and improve the cardiac function， demonstrating remarkable clinical effects. In recent years， the research on the treatment of chronic heart failure based on the inhibition of cardiomyocyte apoptosis is increasing and becomes the current research hotspot. On the basis of literature review， this paper discovers that TCM regulates apoptosis factors and multiple signaling pathways to inhibit apoptosis and inflammation and delay the progression of chronic heart failure through classical pathways such as the death receptor pathway， the mitochondrial pathway， and the endoplasmic reticulum pathway. At the same time， the studies in this field have the following problems： Repeated studies with shallow， simple， and fragmented contents， treating animal models with TCM prescriptions without syndrome differentiation， treating diseases with drugs at only one concentration which is insufficient to indicate efficacy， and lacking comprehensive， holistic， and systematic studies on the relationships of apoptosis with inflammatory responses， pyroptosis， ferroptosis， and autophagy. In the future， more scientific， reasonable， comprehensive， and feasible experimental schemes should be designed on the basis of comprehensively mastering the research progress in this field， and the communication and cooperation between researchers in different disciplines should be strengthened. The specific pathological mechanism of cardiomyocyte apoptosis in chronic heart failure and the signaling pathways， active components， and action targets of TCM in inhibiting cardiomyocyte apoptosis in chronic heart failure should be elucidated. Such efforts are expected to provide sufficient reference for the clinical treatment of chronic heart failure.

ObjectiveTo investigate the potential mechanism of the Jianpi Yishen Huatan Formula （健脾益肾化痰方，JPYSHF） in treating squamous cell lung cancer through the LncRNA ALAL-1/USP4/HDAC2 signaling pathway. MethodsForty Sprague-Dawley （SD） rats were randomly divided into a control group and high-， medium-， and low-dose JPYSHF group with 10 rats in each group. Rats in the JPYSHF groups were administered JPYSHF concentrated liquid at doses of 45， 30， and 15 g/（kg·d） via intragastric gavage， respectively， while the control group received 10 ml/（kg·d） of normal saline， once daily for 10 consecutive days before preparation of drug containing serum. Human lung squamous carcinoma SK-MES-1 cells were divided into a control group and low-， medium-， and high-dose JPYSHF-medicated serum groups. The control group was cultured with 10% saline-containing serum， while the JPYSHF groups were cultured with 10% low-， medium-， or high-dose medicated serum. After 48 hours of incubation， flow cytometry was used to detect apoptosis rates， and a cell scratch assay was performed to evaluate migration areas at 0 h and 24 h to calculate migration rate. Additional SK-MES-1 cells were divided into control serum， JPYSHF-medicated serum （low-， medium-， high-） dose， LncRNA-silenced group （transfected with ALAL-1 siRNA）， USP4-inhibited group （treated with 35 μmol/L PR-619， a deubiquitinase inhibitor）， and HDAC2-inhibited group （treated with 60 μmol/L Vorinostat）. After 24 and 48 hours of culture， cell viability was assessed using the CCK-8 assay； LncRNA ALAL-1， USP4， and HDAC2 mRNA levels were quantified by qPCR after 24 hours； USP4 and HDAC2 protein levels were measured by Western Blot after 48 hours. ResultsCompared with the control serum group， the total apoptosis rate of cells in middle- and high-JPYSHF-medicated serum group significantly increased， and the cell migration rate of cells in the low-， middle- and high-JPYSHF-medicated serum group significantly decreased （P＜0.05 or P＜0.01）. The cell migration rate of the low-， medium- and high-JPYSHF-medicated serum groups decreased with the increase of concentration in a concentration-dependent manner （P＜0.05 or P＜0.01）. Compared with the control serum group at the same time， the cell viability at 24 h and 48 h significantly decreased in all groups （P＜0.05 or P＜0.01）. Compared with the low-JPYSHF-medicated serum group at the same time， the cell viability at 24 h and 48 h also decreased in the high-JPYSHF-medicated serum group and the LncRNA silencing group （P＜0.05）. Compared with the control serum group， the expression of USP4 and HDAC2 mRNA reduced in the low- and medium-dose JPYSHF-medicated serum groups and the USP4 inhibitor group， and the expression of LncRNA ALAL-1， USP4 and HDAC2 mRNA reduced in the high-dose JPYSHF-medicated serum group and LncRNA-silencing group， and HDAC2 mRNA expression reduced in the HDAC2 inhibitor group. USP4 and HDAC2 protein levels were reduced in cells of all groups except for USP4 protein level in HDAC2 inhibitor group （P＜0.05 or P＜0.01）. ConclusionJPYSHF-medicated serum inhibits proliferation and promotes apoptosis of human lung squamous carcinoma cells， and its mechanism of action may be related to its inhibition of the LncRNA ALAL-1/USP4/HDAC2 pathway， with best effect at a high concentration.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

Background: Automated insulin delivery (AID) systems studies are upsurging, half of which were published in the last 5 years. We aimed to evaluate the efficacy and safety of AID systems in patients with type 1 diabetes mellitus (T1DM). Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until August 31, 2023. Randomized clinical trials that compared AID systems with other insulin-based treatments in patients with T1DM were considered eligible. Studies characteristics and glycemic metrics was extracted by three researchers independently. Results: Sixty-five trials (3,623 patients) were included. The percentage of time in range (TIR) was 11.74% (95% confidence interval [CI], 9.37 to 14.12; P<0.001) higher with AID systems compared with control treatments. Patients on AID systems had more pronounced improvement of time below range when diabetes duration was more than 20 years (–1.80% vs. –0.86%, P=0.031) and baseline glycosylated hemoglobin lower than 7.5% (–1.93% vs. –0.87%, P=0.033). Dual-hormone full closed-loop systems revealed a greater improvement in TIR compared with hybrid closed-loop systems (–19.64% vs. –10.87%). Notably, glycemia risk index (GRI) (–3.74; 95% CI, –6.34 to –1.14; P<0.01) was also improved with AID therapy. Conclusion AID systems showed significant advantages compared to other insulin-based treatments in improving glucose control represented by TIR and GRI in patients with T1DM, with more favorable effect in euglycemia by dual-hormone full closedloop systems as well as less hypoglycemia for patients who are within target for glycemic control and have longer diabetes duration.

Conventional surgical management of pelvic fractures entails incision and reduction with internal fixation, a procedure associated with significant bleeding, trauma, and a high surgical risk. The advent of advanced imaging techniques and sophisticated surgical instruments has led to a paradigm shift towards minimally invasive surgery as the prevailing treatment modality for such injuries. The efficacy of reduction is pivotal in determining the clinical prognosis of pelvic fractures, underscoring the importance of enhancing the quality of reduction in the minimally invasive surgery. The advent of 3D printing technology, intelligent orthopaedic surgical robots, mixed reality augmentation technology and high-precision optical localization tracking has catapulted minimally invasive pelvic fracture reduction to the forefront of research in the field of orthopaedics. Studies have demonstrated encouraging outcomes. This paper reviews relevant literature, mainly focusing on the evaluation and measurement, open reduction techniques, minimally invasive closed reduction techniques, and surgical robot assisted reduction techniques in treatment of pelvic fractures, to summarize the technical research progress in minimally invasive closed surgical reduction for pelvic fractures.

Pelvic fractures, the most severe bone trauma, account for approximately 3% of all fractures. As they are caused by high-energy injuries, their rates of mortality and disability are high. Over the past two centuries, the treatment strategies for these fractures have evolved from conservative therapy to open reduction and plate fixation, then to closed reduction and percutaneous screw fixation, and recently to screw fixation assisted by artificial intelligence. In the past 40 years, constant progress has been made in the treatment of pelvic fractures. It is generally acknowledged that a personalized treatment plan should be formulated based on each patient's age, fracture type, comorbidities, functional requirements and other factors when an appropriate treatment mode is chosen. The primary aim of treatment is to accelerate functional recovery, decrease the rate of disability after injury, and improve the quality of daily life of the patient. This paper reviews the treatment history of pelvic fractures, discusses the advantages and disadvantages of current treatment options, and looks ahead to future prospects, aiming to offer valuable references for related clinical practice.

Objective:To explore the clinical efficacy and safety of endoscopic multi-band ligation (EMBL) in the management of refractory gastroesophageal reflux disease (RGERD) combined with esophageal hiatal hernia (HH).Methods:This study was a prospective, multicenter, small-sample cohort study. Patients who were diagnosed as having RGERD combined with HH at Inner Mongolia Medical University Cancer Hospital and Inner Mongolia Medical University Hospital from January 2020 to June 2022 were selected to undergo EMBL. The 24-hour esophageal pH monitoring and high-resolution manometry (HRM) related indicators, gastroesophageal reflux index (GERI), gastroesophageal reflux disease questionnaire (GERD-Q) scores, and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores were compared before and after the operation. The patient satisfaction and complications were also investigated.Results:A total of 25 patients were included, all of whom were successfully treated with EMBL. Reflux symptoms were relieved to varied degrees in all patients. There were no serious complications during or after the operation, such as perforation, bleeding, and dysphagia. Postoperative follow-up at 6 and 12 months showed a significant decrease in DeMeester scores [18.00 (5.83, 54.75) points, 16.30 (4.38, 60.00) points] compared to preoperative baseline [105.00 (60.80, 147.70) points, Z=-3.72, P<0.001; Z=-3.82, P<0.001]. The percentage of time of pH<4 [8.80 (6.10, 11.80)%, 8.95 (5.15, 10.90)%] significantly decreased compared to the baseline [31.15 (16.75, 54.75)%, Z=-3.72, P<0.001; Z=-3.72, P<0.001], the number of long refluxes [7.90 (4.93, 11.75) times, 6.90 (4.00, 10.75) times] significantly decreased compared to the baseline [33.00 (13.00, 43.00) times, Z=-3.82, P<0.001; Z=-3.58, P<0.001], and the number of acid refluxes (14.86±8.71 times, 12.93±5.51 times) significantly decreased compared to before (30.42±17.99 times, t=5.88, P<0.001; t=4.79, P<0.001). Lower esophageal sphincter resting pressure [9.70 (5.80, 19.58) mmHg, 11.70 (5.40, 19.78) mmHg] was significantly higher compared to before [4.70 (3.25, 7.00) mmHg, Z=-2.84, P<0.001; Z=-3.10, P<0.001]. GERD-Q scores (10.00±2.01 points, 9.43±1.74 points) were significantly higher compared to before (15.34±1.51 points, t=8.90, P<0.001; t=9.87, P<0.001), GERD-HRQL scores [7.00 (5.00, 7.75) points, 6.00 (5.75, 8.25) points] significantly decreased compared to preoperative baseline [13.50 (11.00, 21.25), Z=-3.73, P<0.001; Z=-3.72, P<0.001], and GERI (2.26%±1.58%, 2.07%±1.17%) significantly decreased compared to before (5.72%±2.27%, t=8.92, P<0.001; t=9.86, P<0.001). At 6 and 12 months postoperative follow-up, patient satisfaction [68.00% (15/25), 84.00% (21/25)] significantly increased compared to before [0.00% (0/25), Z=-4.63, P<0.001; Z=-6.48, P<0.001]. Conclusion:Preliminary small-sample study has shown that EMBL is safe, reliable and effective for the treatment of RGERD with HH.