Objective To establish a high-performance liquid chromatography method to detect empagliflozin and related substances in empagliflozin bulk drug and tablets,and to provide technical support for quality control and unified monitoring of empagliflozin bulk drug and its tablets.Methods A liquid chromatography development system with the full factorial design of experiments and the Box-Behnken model was used to screen and optimize the chromatographic parameters.Related substances were detected in empagliflozin API and empagliflozin tablets from different companies with the optimized chromatographic parameters.Results The optimized chromatographic parameters were obtained:Shim-pack GIST C18-AQ column(250 mm×4.6 mm,5 μm)was used,column temperature was 15 ℃,gradient elution with water-acetonitrile as mobile phase was as below,flow rate was 1.2 mL·min-1,detection wavelength was set at 224 nm.The specificity of the method is good,with recoveries ranging from 94.8％to 101.7％,and RSD ranging from 0.5％to 3.1％.The known single impurity in APIs and tablets is less than 0.05％,any other unknown single impurity is less than 0.06％,and the total amount of impurities are less than 0.3％.The related substances of supervised sampling are under good control.Conclusion The method is reliable and robust for determining related substances of empagliflozin and its tablets.

Objective To investigate the effects of emergency endovascular treatment on the short-term and long-term prognosis of patients with minor stroke(National Institutes of Health stroke scale[NIHSS]score≤5)caused by posterior circulation large vessel occlusion(LVO).Methods A retrospective analysis was performed on consecutive patients with minor stroke caused by posterior circulation LVO admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University from July 2019 to March 2024.The patients were divided into the emergency endovascular treatment group and the standard medical treatment group according to the treatment method.Baseline and clinical data were collected from all patients enrolled,including age,sex,smoking history,history of alcohol consumption,medical history(hypertension,diabetes,hyperlipidemia,atrial fibrillation,transient ischemic attack[TIA],blood pressure on admission,stroke history,coronary heart disease),intravenous thrombolysis,tandem lesions,posterior circulation Alberta stroke program early CT score(pc-ASPECTS)on admission,NIHSS score on admission and discharge,time from onset to admission,responsible occluded vessel(basilar artery,left vertebral artery,right vertebral artery),vertebral artery development(left vertebral artery dominant,right vertebral artery dominant,bilateral vertebral artery dominant),non-lesion side vertebral artery development(poor,good,not applicable),basilar artery on CT angiography(BATMAN)score,leptomeningeal branch compensation(open,not open),surgery-related indicators(number of thrombectomy passes[≤2 times,＞2 times],rescue interventions[stent placement,balloon dilation,arterial thrombolysis,intra-arterial tirofiban infusion],immediate postoperative modified thrombolysis in cerebral infarction[mTICI]grade≥2b[successful recanalization],anesthesia method[general,local],endotracheal intubation status[yes,no],duration of mechanical ventilation[not using a ventilator or successfully intubation for≤24 hours and＞24 hours]),in-hospital systematic complications(deep-vein thrombosis,urinary tract infection,lung infection).The primary outcome for short-term prognosis was an excellent outcome(modified Rankin scale[mRS]score of 0-1)within 90 days after onset.Secondary outcomes included a good outcome(mRS score of 0-2)within 90days after onset,recurrent ischemic stroke within 90 days after onset,all-cause mortality within 90 days after onset.Safety outcomes were symptomatic intracerebral hemorrhage(sICH)within 24 hours of treatment(NIHSS score increased by≥4 points or increased level of consciousness score by≥1 point compared with admission,with visible hemorrhagic lesions on follow-up CT scan)and early neurological deterioration(END,NIHSS score increased by≥2 points or motor score increased by≥1 point compared with admission,within 24 hours after treatment).Long-term outcome was defined as recurrent ischemic stroke within 1 year after onset.Short-term and safety outcomes were compared between the emergency endovascular treatment group and the standard medical treatment group.Kaplan-Meier survival curves was used to evaluate the effect of emergency endovascular treatment on the long-term prognosis.Based on the mRS score at 90 days from onset,all patients were divided into an excellent outcome(mRS score 0-1)group and a non-excellent outcome(mRS score 2-6)group.Baseline and clinical data were compared across the two groups.Variables with statistically significant differences were included in the multivariate Logistic regression analysis to investigate the influencing factor of 90-day excellent outcomes in patients with minor stroke caused by posterior circulation LVO.Results A total of 56 patients with minor stroke caused by posterior circulation LVO were enrolled,including 18 patients in the emergency endovascular treatment group and 38 patients in the standard medical treatment group.45 patients achieved excellent outcomes and 11 patients achieved non-excellent outcomes.(1)The emergency endovascular treatment group had lower pc-ASPECTS on admission(8.0[7.0,9.0]points vs.9.0[8.0,10.0]points,P=0.043)and There were no statistically significant differences in the excellent outcome rate,good outcome rate,and ischemic stroke recurrence rate within 90 days after onset between the two groups(all P＞0.05).No all-cause mortality occurred within 90 days after onset in either group.In the emergency endovascular treatment group,one patient developed sICH and one developed END within 24 hours after treatment.(3)No recurrent ischemic stroke in the emergency endovascular treatment group within 1 year after onset,while 3cases(7.89%)of recurrence were observed within 1year after onset in the standard medical treatment group.The Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the incidence of ischemic stroke within one year after onset between the two groups(P=0.341).(4)There were statistically significant differences between patients with excellent outcome and patients with non excellent outcome in drinking history,diabetes history,NIHSS score after discharge,distribution of responsible occlusive vessels,and distribution of vertebral artery development(all P＜0.05).The results of multivariate Logistic regression analysis showed that the NIHSS score at discharge was an independent influencing factor for excellent outcome at 90 days after onset in patients with minor stroke caused by posterior circulation LVO(OR,0.448,95%CI 0.275-0.728,P=0.001).Conclusions This study shows potential safety and effectiveness of emergency endovascular treatment on patients with minor stroke caused by posterior circulation LVO,but it is not superior to standard medical treatment in terms of short-term and long-term outcomes.Further large-sample randomized controlled trials are warranted to validate the findings of this study.

Objective To investigate the factors influencing global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods Clinical data of 315 hospitalized patients diagnosed with acute STEMI who underwent percutaneous coronary intervention(PCI)at the First Medical Center of Chinese PLA General Hospital from June 2016 to September 2021 were retrospectively collected.After analyzing CMR images of all patients,GLS and other strain parameters were obtained,and then the patients were divided into two groups according to the median GLS.In order to balance gender and age differences,1:1 propensity score matching was performed,and 206 patients were eventually included:GLS>-11.3%group(indicating severe GLS impairment,n=103)and GLS≤-11.3%group(n=103).Baseline characteristics,laboratory indicators,coronary angiographic parameters,electrocardiogram(ECG)features,and CMR parameters were compared between the two groups.Variables showing significant differences were analyzed for their correlation with GLS.Multivariate logistic regression and multiple stepwise linear regression analyses were performed to identify factors associated with GLS impairment.Results Compared with GLS≤-11.3%group,GLS>-11.3%group had significantly higher peak levels of creatine kinase-MB(CK-MB)and troponin T(TnT)(P<0.001).A higher proportion of patients in GLS>-11.3%group had the left anterior descending artery(LAD)as the culprit vessel,while a lower proportion had the right coronary artery(RCA)as the culprit vessel(P<0.001).Additionally,GLS>-11.3%group had longer QRS duration(P<0.001)and a higher incidence of pathological Q waves(P=0.001).Regarding CMR parameters,GLS>-11.3%group exhibited larger global circumferential strain(GCS),infarct size(IS),and left ventricular end-systolic volume(LVESV),as well as lower global radial strain(GRS)and left ventricular ejection fraction(LVEF)(P<0.001).Multivariate logistic regression indicated that peak TnT(OR=1.092,P=0.001),LAD culprit vessel(OR=3.744,P<0.001),and QRS duration(OR=1.026,P<0.001)were significantly associated with severely impaired GLS.Multiple stepwise linear regression analysis showed that the logarithmic value of peak TnT,LAD as the culprit vessel,and the square root of QRS duration were linearly correlated with GLS values(adjusted R2=0.301,P<0.001),and these independent variables explained 30.1%of the variation in GLS.Conclusion Elevated peak TnT,prolonged QRS duration,and LAD as the culprit vessel are significantly associated with severe GLS impairment in STEMI patients,indicating more severe myocardial infarction and worse left ventricular function.

Objective To investigate the effects of transcutaneous auricular vagus nerve stimula-tion(taVNS)on preoperative anxiety and sleep quality in patients undergoing laparoscopic myomecto-my.Methods A total of 106 patients scheduled for elective laparoscopic myomectomy were randomly divided into active stimulation group(a-taVNS group,n=53)and sham stimulation group(s-taVNS group,n=53).Trait Anxiety Inventory(TAI)scores,State Anxiety Inventory(SAI)scores,Hos-pital Anxiety and Depression Scale-anxiety(HADS-A)scores,Amsterdam Preoperative Anxiety and Information Scale-anxiety(APAISa)scores,Athens Insomnia Scale(AIS)scores,hemodynamic parameters,and adverse reactions were evaluated before intervention(T0),30 min after interven-tion(T1),and the next morning(T2).The degrees of anxiety improvement(△SAI=SAIT0-SAIT1;△HADS-A=HADS-AT0-HADS-AT1;△APAISa=APAISaT0-APAISaT1)and sleep improvement(△AIS=AIST0-AIST2)were calculated,and their correlations were assessed.Results At T0,there were no significant differences in SAI,HADS-A,and APAISa scores between the two groups(P=0.376,0.682,0.144).At T1,there were significant differences in SAI and HADS-A scores between the two groups(adjusted P＜0.05),while there was no significant difference in APAISa scores(P=0.141).Compared with the s-taVNS group,the a-taVNS group had higher improvement values of △SAI,△HADS-A,and △APAISa(P＜0.001).Compared with T0,the AIS score de-creased and the incidence of sleep disorders decreased at T2 in the a-taVNS group(P＜0.05).Compared with the s-taVNS group,the AIS score and the proportion of patients with sleep disorders decreased at T2 in the a-taVNS group(P＜0.05).There was a positive correlation between the de-gree of anxiety improvement and the degree of sleep improvement in the a-taVNS group(P＜0.05),while there was no significant correlation in the s-taVNS group(P＞0.05).Compared with T0,sys-tolic blood pressure,diastolic blood pressure,and heart rate decreased at T1 in both groups,but there were no significant differences in these parameters between the two groups(P＞0.05).During the study period,no adverse events such as tinnitus,dizziness,headache,nausea,vomiting,or fa-cial flushing occurred in either group.Conclusion The method taVNS can improve preoperative anxiety and reduce the incidence of sleep disorders in patients undergoing laparoscopic myomectomy.

Objective To compare the effects of different doses of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet in the treatment of cough variant asthma(CVA)and the improvement of airway function and inflammatory factors.Methods Elderly patients with cough variant asthma were randomly divided into group A and group B.Both groups of patients received budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet.Group A was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),2 inhalation per time,twice a day;Group B was given budesonide and formoterol fumarate powder for inhalation,4 inhalation per time,twice a day;budesonide fumatrol inhalation powder mist for continuous treatment for 6 months,and montelukast sodium tablet 10 mg once a day for at least 3 months.The nighttime cough scores of the two groups were compared before treatment and after treatment.The percentage of forced expiratory volume in one second(FEV1)in the predicted value,the maximum mid expiratory flow(MMEF),the fractional exhaled nitric oxide(FeNO),interleukin-5(IL-5)and eosinophils were compared between the two groups.The incidence of adverse drug reactions and the recurrence rate within 1 year were compared between the two groups.Results A total of 45 cases were enrolled in both the group A and the group B.At 9 months after treatment,the nocturnal cough scores of the group A and the group B were(0.93±0.42)and(0.65±0.29)points,respectively;the percentage of FEV1 in the predicted value were(97.75±9.67)％and(100.93±11.06)％,respectively;the MMEF values were(2.81±1.04)and(3.08±1.09)L·s-1,respectively;the FeNO values were(18.94±9.75)and(15.94±7.96)ppb,respectively;the IL-5 levels were(10.88±7.06)and(8.11±5.56)pg·mL-1,respectively.The above indicators in group B showed statistically significant differences compared to group A(all P＜0.05).The total incidence of adverse drug reactions in group A and group B were 8.89％(5 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.The recurrence rates was 15.56％(7 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.There was no statistically significant difference in the above indicators between group B and group A(all P＞0.05).Conclusion For elderly patients with CVA,higher dose of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet can better improve cough symptoms,reduce the level of airway hyperresponsiveness and inflammatory factors,reduce the recurrence rate,and the patients are well tolerated.

Objective:Varicocele(VC)induces male infertility by mediating changes in the testicular microenvironment,in which testicular hypoxia and high-pressure are important pathological conditions.This study aims to compare the mouse spermatogenesis(GC-2spd)cells and Sertoli(TM4)cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling,and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model.Methods:On the basis of cell hypoxia induced by CoCl2,the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution.After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model,the cells were divided into normal group,hypoxia model group and composite model group.And the levels of OS,programmed cell death,inflammatory factors,and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods.Results:The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L,respectively,and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg(P＜0.05).Compared with the normal group,the SOD levels of GC-2 and TM4 cells decreased(all P＜0.05),CAT level decreased(all P＜0.05),and MDA level increased(all P＜0.01),and the OS level of GC-2 and TM4 cells was more obvious than that of the hy-poxia model group(all P＜0.05).Compared with the normal group,apoptosis occurred in GC-2 and TM4 cells after composite model-ing(all P＜0.05).Compared with the normal group,the mRNA expressions of IL-1β,IL-18,TNF-α and COX-2 in GC-2 and TM4 cells significantly increased(P＜0.01)and higher than those in hypoxia model group(P＜0.05)and induced pyroptosis(P＜0.01).The expression level of GSDMD increased(P＜0.05).Conclusion:The cell model with hypoxia and high pressure com-bined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone,but also further cause in-flammatory response damage and pyroptosis,which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC.This cell model can be used for studying the pathogenesis of VC-associated male infertility,evalu-ating drug efficacy,and exploring pharmacological mechanisms.

Porcine arthritis,one of the common chronic diseases in large-scale pig farms,can signifi-cantly reduce the production performance of meat pigs.In this study,a strain of Haemophilus pa-rasuis(HPS)was isolated from the joint fluid of a lame pig.The HPS was analyzed in terms of se-rotypes,virulence genes,and resistance genes.Additionally,it was treated with sensitive antibiotics to provide a theoretical basis for the comprehensive prevention and treatment of arthritis in meat pigs in future production settings.A strain of HPS type 14 was isolated from the joint fluid of dis-eased pigs.The HPS isolate demonstrated sensitivity to β-lactams and tetracyclines,while florfeni-col and polymyxin effectively inhibited its growth at low concentrations.However,the bacteria ex-hibited resistance to sulfonamides and ciprofloxacin.The treatment of affected pigs with clinical ar-thritis using doxycycline and enrofloxacin injections proved effective.Compared to the infected group,in which the sick pigs experienced difficulty flexing their carpal and tarsal joints and exhibi-ted significant lameness,the pigs in the treatment group showed marked improvement.Their joints were only slightly swollen,and the clinical symptoms of arthropathy were alleviated.

BACKGROUND:Current strategies for the treatment of the corticospinal tract after spinal cord injury mainly focus on exercise rehabilitation,drug therapy,transcranial magnetoelectric stimulation,endogenous regulation such as transcription factors and specific signaling pathways.Among them,transcription factors and their specific signaling pathways are the key factors regulating the axonal regeneration of corticospinal tract after spinal cord injury.A large number of preclinical studies have confirmed that the synergy between transcription factors and their signaling pathways has a significant regulatory effect on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.Therefore,it has broad application prospects to explore new combination therapy strategies targeting transcription factors and specific signaling pathways for spinal cord injury.OBJECTIVE:To systematically summarize the regulatory effects of transcription factors and their signaling pathways on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury and the underlying molecular mechanisms,and explore the application of combined therapy strategies targeting transcription factors and signaling pathways in the neuroplasticity of the corticospinal tract after spinal cord injury,in order to provide a new combination strategy for the treatment of spinal cord injury.METHODS:The search terms included"spinal cord injury,axon regeneration,transcription factors,signaling pathway,corticospinal tract,central nervous system,synergistic system,neuroprotective system"in Chinese and English.A literature retrieval was conducted in WanFang,Web of Science,and PubMed for relevant literature published from database inception to September 2024.Finally,101 articles were included for analysis and summary.RESULTS AND CONCLUSION:(1)The article outlines the biological properties and intervention strategies for axonal regeneration of the corticospinal tract after spinal cord injury,analyses the reasons for focusing on the corticospinal tract after spinal cord injury,and elucidates the response and possibility of regeneration of the corticospinal tract after spinal cord injury.(2)In this study,the combined regulatory strategy of transcription factors centered on Krüppel-like factor 6,Krüppel-like factor 7,and neuronal restriction silencing factor can significantly promote the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.(3)The phosphatidylinositol 3-kinase-protein kinase B-rapamycin target protein signaling pathway and Wnt5a pathway are the classical signaling pathways fortranscription factors to regulate the axonal regeneration of corticospinal tract neurons,and the combined treatment strategy can effectively promote the axonal regeneration and functional reconstruction of corticospinal tract neurons after spinal cord injury.(4)This article discusses the combined treatment strategies of transcription factors and specific signaling pathways in a comprehensive and detailed manner,such as Krüppel-like factor 6 combined with signal transducer and activator of transcription 3,Krüppel-like factor 7 combined with SOX11 transcription factor,combined inhibition of phosphatase and tensin homologs and neuronal restriction silencing factor,etc.,to exert a synergistic effect and promote the axonal regeneration of corticospinal tract neurons after spinal cord injury,which are significantly better than those of single treatment.It can effectively improve functional recovery and provide a reference scheme for the future treatment of axonal regeneration of corticospinal tract neurons after spinal cord injury.However,the specific mechanism of the combination therapy still needs to be further studied,and the current combination strategy is only widely used in animal models but not in clinical practice.(5)The combined therapy strategy based on transcription factors and specific signaling pathways has a significant therapeutic effect on the axonal regeneration of corticospinal tract neurons after spinal cord injury,and it is necessary to further explore the molecular mechanism of joint regulation in the future,in order to provide an effective combined therapy strategy for the rehabilitation and functional reconstruction of spinal cord injury.

Objective To explore the effect of transcutaneous auricular vagus nerve stimulation(taVNS)on postoperative recovery of gastrointestinal function in gynecological laparoscopic surgery patients.Methods Ninety-six patients who underwent elective laparoscopic total hysterectomy were selected.According to the random number table method,patients were divided into the taVNS group(group T)and the sham stimulation group(group F)with 48 patients in each group.The conventional general anesthesia method was used in both groups.The group T received taVNS once before surgery and once in the anaesthesia recovery room with 30 min per stimulation,while the group F was given sham stimulation for 30 min each.Postoperative recovery time of anal gas and defecation,the I-FEED scores on the 1st,2nd and 3rd postoperative days,the GSRS score on the 3rd postoperative day were recorded.The NRS scores on the 1st and 2nd postoperative days,postoperative remedial analgesia,occurrence of postoperative adverse effects and duration of postoperative hospitalization were recorded.Results Compared with the group F,the time to first postoperative anal exhaust and defecation was significantly shorter in the group T.The I-FEED scores on the 1st,2nd and 3rd postoperative days,and the GSRS score on 3rd postoperative day were significantly decreased in the group T.The proportion of patients with postoperative gastrointestinal intolerance and postoperative gastrointestinal dysfunction were reduced in the group T(P＜0.05).NRS scores at postoperative days 1,and 2 were decreased and the incidence of postoperative nausea was lower(P＜0.05).There were no significant differences in postoperative remedial analgesia,the occurrence of postoperative vomiting,dizziness,bradycardia and hypotension,and duration of postoperative hospitalization in the two groups of patients(P＞0.05).Conclusion taVNS can improve the recovery of postoperative gastrointestinal function,reduce postoperative nausea and alleviate postoperative pain in laparoscopic total hysterectomy patients.

Objective To study the efficacy of hemoperfusion(HP)in series with continuous renal replace-ment therapy(CRRT)integrated combined blood purification under extracorporeal citrate anticoagulation in the treatment of severe hypertriglyceridemic acute pancreatitis(HTG-AP).Methods A total of 62 patients with severe HTG-AP admitted to the Affiliated Hospital of Xuzhou Medical University from June 2022 to May 2024 were selected and randomly divided into control group and observation group,with 31 cases in each group.The control group was treated with conventional medical treatment+HP combined with CRRT staged combined blood purifica-tion treatment,and the observation group was treated with conventional medical treatment+HP in series with CRRT integrated combined blood purification treatment under extracorporeal citrate anticoagulation.The indexes and clinical efficacy before and 7 days after treatment were compared between the two groups.Results The single CRRT time of the observation group was longer than that of the control group,and the frequency of CRRT was less than that of the control group(P<0.05).There were no significant differences in the total CRRT time,single HP time,HP frequency and total HP time between the two groups(P>0.05).The blood routine,inflammatory factors,blood biochemistry and clinical scores of the two groups after treatment were improved compared with those before treatment(P<0.05).After treatment,the hemoglobin(Hb)and platelet count(Plt)of the observation group were higher than those of the control group(P<0.05),and there were no significant differences in other indexes of blood routine,inflammatory factors,blood biochemistry and clinical scores between the two groups(P>0.05).There were no significant differences in clinical indexes,prognosis and complications between the two groups(P>0.05).Conclusions Without affecting the efficacy,HP in series with CRRT integrated combined blood purification under extracorporeal citrate anticoagulation in the treatment of severe HTG-AP can prolong the use time of CRRT blood filter and pipeline,reduce the use of consumables,reduce the risk of bleeding,and avoid multiple catheter removal of HP and CRRT operation separately,and reduce the risk of related infection.It is worthy of clinical application.