ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla （TFA） treat immunoglobulin A （IgA） nephropathy （IgAN） through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups （n=10）： blank， model， low-dose TFA （TFA-L， 27 mg·kg^-1）， medium-dose TFA （TFA-M， 54 mg·kg^-1）， high-dose TFA （TFA-H， 108 mg·kg^-1）， and losartan potassium （LST， 4.5 mg·kg^-1） groups. The remaining five groups， excluding the blank group， were modeled with bovine serum albumin （BSA）， lipopolysaccharide （LPS）， and carbon tetrachloride （CCl₄）. Specifically， from weeks 1 to 10， BSA was administered via gavage every other day， and a mixture of castor oil and CCl₄ was injected subcutaneously once a week， with LPS injected into the tail vein at weeks 6 and 8. After successful modeling， each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein （24 h UP） and serum creatinine （SCr） were quantified by kits， and the serum IgA level was determined by enzyme-linked immunosorbent assay （ELISA）. Renal pathological changes were observed by hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. Renal IgA deposition was assessed by immunofluorescence （IF）. Endoplasmic reticulum （ER） stress was observed by transmission electron microscopy. Western blot and immunohistochemistry （IHC） were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis， and key metabolites arachidonic acid （AA）， prostaglandin E₂ （PGE₂）， and cyclooxygenase-2 （COX-2） were validated. ResultsCompared with the blank group， the model group showed increased 24-hour urine protein （24 h UP） and serum creatinine （SCr） levels （P<0.01）， obvious renal pathological damage， elevated serum IgA level （P<0.01）， increased renal AA and PGE₂ levels （P<0.01）， and up-regulated protein levels of COX-2， glucose-regulated protein 78 （GRP78）， phosphorylated eukaryotic initiation factor 2α （P-EIF2α）， activating transcription factor 4 （ATF4）， inositol-requiring enzyme 1α （IRE1α）， and spliced X-box binding protein 1 （XBP1s） in the renal tissue （P<0.05， P<0.01）. Compared with the model group， the intervention groups showed reductions in 24 h UP and SCr levels （P<0.05， P<0.01）， alleviated renal pathological injury， decreased serum IgA level （P<0.05， P<0.01）， and reduced renal AA and PGE₂ levels （P<0.01）. Western blot and IHC results showed that TFA reduced the levels of COX-2， GRP78， P-EIF2α， ATF4， IRE1α， and XBP1s in the renal tissue （P<0.05， P<0.01）. Metabolomics results indicated that 51 commonly differential metabolites were found among the normal， model， and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid， prostaglandin 2α， leukotriene B₄， leukotriene D₄， among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway， thereby modulating ER stress， reducing renal damage， and ameliorating IgA nephropathy.

ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

Objective To investigate the association between antenatal white blood cell count(WBC)and the risk of histological chorioamnionitis(HCA)in pregnant women with late pregnancy premature rupture of membranes(PROM).Methods A retrospective analysis was performed on totally 118 pregnant women with PROM in late pregnancy from March 2018 to August 2021 in the hospital.They were divided into HCA group and non-HCA group according to the presence or absence of HCA.The general clinical data,laboratory indica-tors and delivery outcomes of the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the association between prenatal WBC and HCA risk.Generalized additive models were used for curve fitting,and segmented regression models were used to further explain the nonlinear relationship between maternal prenatal WBC and HCA risk.Results The prenatal WBC of the HCA group was signifi-cantly higher than that of the non-HCA group(P＜0.001).After adjusting for covariates,elevated prenatal WBC increased the risk of HCA,with an OR of 1.190(95％CI:1.006-1.406,P=0.042).Curve fitting showed that there was a nonlinear relationship between prenatal WBC and HCA risk,and the log-likelihood ratio test of WBC at the inflection point 13.5×109/L(95％CI:11.75-14.56)was statistically significant(P=0.029).For the three groups of prenatal WBC,the risk of HCA in pregnant women gradually increased with the increase of WBC level,which was 0.314(95％CI:0.200-0.456)in the normal group,0.439(95％CI:0.252-0.645)in the high group,and 0.682(95％CI:0.354-0.893)in the elevated group.Conclusion The higher the prenatal WBC of pregnant women with PROM in late pregnancy,the greater the risk of HCA,but there is no simple linear relationship between the two,and there is a threshold effect.

The sealing performance is directly related to the safety,reliability and mission success rate of aerospace equipment.The sealing performance of rubber seals and the optimized design of the compression force directly affect the performance and work efficiency of the equipment.Based on the hyperelastic Mooney-Rivlin model of nonlinear materials,the mechanical properties of rubber are simulated,and a finite element model of rubber seals is established.Through simulation analysis,the effects of different cross-section dimensions and compression amounts on the sealing performance are studied and compared,and key parameters such as the contact stress distribution,maximum contact stress,and compression force.The size of the fillet affects the final deformation and the contact state.By optimizing the geometric parameters,the compression force can be reduced while ensuring the sealing performance,providing a theoretical basis for the optimized design of rubber seals.

Objective:To evaluate the effect of preoperative oral carbohydrate intake on postoperative nausea and vomiting (PONV) in elderly patients undergoing gynecological laparoscopic surgery.Methods:This study was a randomized controlled trial. One hundred elderly patients, aged≥65 yr, with a body mass index of 18-30 kg/m 2, with American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, who underwent gynecological laparoscopic surgery at the Baoding First Central Hospital from March 2023 to June 2024, were selected. Stratification was conducted by age (65-74 yr/≥75 yr) using an online randomization tool, and the patients were randomly divided into conventional fasting group (group C) and oral carbohydrate group (group P), with 50 cases in each group. Patients took oral carbohydrate drinks of 4 ml/kg at 2 h before operation, with total amount ≤400 ml in group P, while patients received conventional preoperative fasting protocols in group C. The occurrence and severity of PONV within 48 h postoperatively were observed. The visual analogue scale scores for hunger and thirst, State-Trait Anxiety Inventory scale scores, length of stay in the postanesthesia care unit, duration of hospital stay, time to first flatus, time to first ambulation, and patient′s satisfaction were recorded in the two groups. Results:Compared with group C, the incidence and severity of PONV were significantly decreased within 48 h after surgery, the visual analogue scale scores for hunger and thirst and State-Trait Anxiety Inventory scale scores were significantly decreased after entering the operating room, the length of stay in the postanesthesia care unit, time to first flatus and time to first ambulation were significantly shortened, and the patient′s satisfaction was significantly increased in group P ( P<0.05). Conclusions:Oral carbohydrate intake before operation can effectively reduce the occurrence and severity of PONV and improve the quality of postoperative recovery in elderly patients undergoing gynecological laparoscopic surgery.

Objective:To evaluate the effect of preoperative oral carbohydrate intake on postoperative nausea and vomiting (PONV) in elderly patients undergoing gynecological laparoscopic surgery.Methods:This study was a randomized controlled trial. One hundred elderly patients, aged≥65 yr, with a body mass index of 18-30 kg/m 2, with American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, who underwent gynecological laparoscopic surgery at the Baoding First Central Hospital from March 2023 to June 2024, were selected. Stratification was conducted by age (65-74 yr/≥75 yr) using an online randomization tool, and the patients were randomly divided into conventional fasting group (group C) and oral carbohydrate group (group P), with 50 cases in each group. Patients took oral carbohydrate drinks of 4 ml/kg at 2 h before operation, with total amount ≤400 ml in group P, while patients received conventional preoperative fasting protocols in group C. The occurrence and severity of PONV within 48 h postoperatively were observed. The visual analogue scale scores for hunger and thirst, State-Trait Anxiety Inventory scale scores, length of stay in the postanesthesia care unit, duration of hospital stay, time to first flatus, time to first ambulation, and patient′s satisfaction were recorded in the two groups. Results:Compared with group C, the incidence and severity of PONV were significantly decreased within 48 h after surgery, the visual analogue scale scores for hunger and thirst and State-Trait Anxiety Inventory scale scores were significantly decreased after entering the operating room, the length of stay in the postanesthesia care unit, time to first flatus and time to first ambulation were significantly shortened, and the patient′s satisfaction was significantly increased in group P ( P<0.05). Conclusions:Oral carbohydrate intake before operation can effectively reduce the occurrence and severity of PONV and improve the quality of postoperative recovery in elderly patients undergoing gynecological laparoscopic surgery.

Objective:To investigate the effect of anoxic cold environment at 4500 m altitude on female men-struation.Methods:From March 1 to March 20,2023,women in a unit at an altitude of 4500 meters were selected for reproductive health questionnaire survey,and were divided into≤6 months group,6 months to 12 months group and≥12 months group according to altitude exposure time.The changes of menstruation in each group were analyzed to explore the relevant influencing factors.Results:The total incidence of abnormal menstruation in working women in hypoxic cold environment was as high as 66.14%,and there was no statistically significant difference between the groups at different high-altitude exposure times(P＞0.05).The highest incidence of dys-menorrhea among the types of menstrual changes was 61.90%,but there was no statistically significant differ-ence between the groups at different high altitude exposure times(P＞0.05).There was a statistically significant difference(P＜0.05)in the proportion of insufficient sleep for at least 3 days per week,nervousness and anxiety,and training during their menstrual period in the women who experienced changes in their menstrual cycle com-pared to those who did not.Conclusions:Hypoxic cold environment can lead to the change of female menstrua-tion,and it is combined with sleep deficiency,tension and anxiety,and menstrual exercise.

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.

BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.