Aim To explore the underlying molecular mechanism of Alisol A 24-acetate(24A)in improving oxygen-glucose deprivation/reoxygenation(OGD/R)injury in brain microvascular endothelial cells(BMECs)and its correlation with miR-98-5p/transi-ent receptor potential melastatin-2(TRPM2).Meth-ods The ischemia-reperfusion injury in brain micro-vascular endothelial cells(BMECs)was established u-sing bEnd.3 cells subjected to 8 h of oxygen-glucose deprivation followed by 16 h of re-oxygenation.The cells were intervened by miR-98-5p mimics and/or 18.77 μmol·L-1 24A for 24 h and divided into the control group,OGD/R group,OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group and OGD/R+miR-98-5p mimics group.The mRNA levels of miR-98-5p and TRPM2 were detected by qPCR.IL-1 β and TNF-α levels were detected by ELISA.The expression levels of TRPM2,p-AKT,p-GSK3 β,AKT,GSK3 β,Bcl-2,Bax,ZO-1,Occludin,Claudin-5 were detected by Western blot.Apoptosis and reactive oxygen species(ROS)levels were detected by flow cytometry.The targeting relationship between miR-98-5p and TRPM2 was verified using dual luciferase assay.Results Compared with the control group,the apoptosis of OGD/R group was obvious,Bcl-2/Bax decreased,ZO-1,Occludin,Claudin-5 decreased,IL-1 β,TNF-α and ROS increased,miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β decreased but TRPM2 increased.But com-pared with the OGD/R group,except the control group,the other three groups showed the opposite trend in the above aspects;compared with the OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group showed decreased apoptosis,decreased degradation of ZO-1,Occludin and Claudin-5,and decreased inflam-mation and ROS.miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β increased and TRPM2 decreased.However,compared with the OGD/R+24A+miR-98-5p mimics group,the OGD/R+miR-98-5p mimics group reversed this trend.Dual luciferase confirmed that miR-98-5p targeted regulation of TRPM2.Conclusion 24A in-hibits the expression of TRPM2 in BMECs through miR-98-5p,regulates AKT/GSK3β signal pathway,re-duces OGD/R inflammation and oxidative stress-medi-ated apoptosis,prevents the degradation of ZO-1,Oc-cludin and Claudin-5,and improves BBB permeability.

Objective This study aims to investigate controversial cases of forensic clinical re-identification of fractures,exploring the characteristics,causes,and countermeasures related to identification errors in primary bone injuries,complications,and subsequent changes.The goal is to provide identification strategies for similar cases regarding the collection of identification materials,timing,and examination method selection,ultimately establishing a paradigm for such identifications.Methods A total of 103 cases of clinical re-identification of fractures accepted by the West China Forensic Identification Center from 2020 to 2024 were collected,and the data from initial identifications and re-identifications were retrospectively analyzed.Results Male cases accounted for 69.90%of the re-identifications,with disability grade(67.96%)and injury degree(30.10%)being the primary concerns.Individual requests represented a high proportion(92.86%)in the initial assessment of disability levels,while unit or joint requests dominated the re-assessment(92.86%).The agreement rates for disability grade and injury degree were 55.26%and 59.38%,respectively.The reassessment of disability grades primarily involved fractures of limb long bones,spine,and ribs,with 75.53%of opinions resulting in downgraded disability levels.Rib,orbital,and nasal bone fractures were the main focus in injury degree reassessments,with 84.62%of opinions indicating aggravated injuries.The consistency rates for fracture identification in disability grade assessments was 92.21%,while rates for injury degree and sequelae were 65.63%and 48.94%,respectively.Inconsistencies in identifying damage facts—including the presence of fractures,distinguishing between fresh and old fractures,and determining the nature of fractures and sequelae—were primarily noted in rib,orbital,and nasal bone fractures.The utilization rate of CT metadata in initial evaluations(25.00%)was significantly lower than in re-evaluations(95.00%).The identification time for joint mobility dysfunction after fracture in re-identifications was significantly longer than in initial identifications(P=0.0002),and the identification time for cases with agreement was significantly shorter than for cases with disagreement(P=0.036).Conclusion Image data type and identification timing are critical factors that may influence the accuracy and consistency of forensic clinical identification of bone injuries.When necessary,dynamic CT metadata in conjunction with image post-processing technology can be routinely employed to identify fractures of the ribs,orbital bones,or nasal bones,thereby reducing the risk of misidentification.

Objective To explore the value of carotid pulse wave combined with urinary transferrin(TRF)and β2-microglobulin(β2-MG)in the evaluation of renal injury in patients with hyperten-sive nephropathy.Methods A total of 30 patients with hypertensive nephropathy,30 patients with simple hypertension and 90 patients with non-hypertensive nephropathy who were admitted to our hospital between May 2021 and April 2024,and 30 healthy individuals(control group)who taking physical examination during same period were enrolled and assigned into corresponding groups,respectively.According to the severity of renal injury,the 120 patients from the hyperten-sive nephropathy group and non-hypertensive nephropathy group were divided into normal group(28 cases),mildly injured group(36 cases),moderately injured group(31 cases)and severely in-jured group(25 cases).The carotid pulse wave indicators[pulse wave velocity at beginning of the systole(PWV-BS),pulse wave velocity at ending of the systole(PWV-ES)],and urinary TRF and β2-MG levels were detected and compared in above groups.ROC curves were plotted to ana-lyze the diagnostic values of these indicators in hypertensive nephropathy.The relationship be-tween the above indicators and the severity of renal injury was analyzed with sequential multivari-ate logistics regression analysis.Results There were significant differences in PWV-BS,PWV-ES,and urinary TRF and β2-MG levels among the hypertensive nephropathy group,non-hyperten-sive nephropathy group,hypertension group and control group(P＜0.01).ROC curve analysis showed that the AUC value of the four indictors combined together in the diagnosis of hyperten-sive nephropathy was 0.907,which was statistically greater than that of single indicator alone(0.774,0.743,0.728,0.749,P＜0.01).Obvious differences were also observed in PWV-BS,PWV-ES,and urinary TRF and β2-MG levels among the severely,moderately and mildly injured groups and normal group(P＜0.01).Sequential multivariate logistics regression analysis indicated that PWV-BS(OR=1.824,95％CI:1.272-2.616,P=0.001),PWV-ES(OR=1.910,95％CI:1.268-2.877,P=0.002),and urinary TRF(OR=2.442,95％CI:1.485-4.018,P=0.001)and β2-MG levels(OR=2.807,95％CI:1.580-4.984,P=0.001)were influencing factors of renal injury severity in the renal injured patients.Conclusion Carotid pulse wave combined with urinary TRF and β2-MG can be applied in auxiliary diagnosis of hypertensive nephropathy,and they are correla-ted with the severity of renal injury.

Objective To study the economic burden caused by healthcare-associated infection(HAI)in patients with severe acute pancreatitis(SAP),and provide theoretical basis for formulating HAI prevention and control measures.Methods Patients with SAP discharged from a tertiary first-class hospital in Jiangxi Province from July 1,2023 to June 30,2024 were selected as the study subjects.Information including demographic characteristics,clinical data,and hospitalization expense were collected.Patients were divided into a HAI group and a non-HAI group according to HAI occurrence.A propensity score matching(PSM)method was used to conduct a 1∶2 ma-tching,and differences in the length of hospital stay and hospitalization expense between the two groups of patients after PSM were compared.Results A total of 709 patients were included in the analysis,out of which 65 cases ex-perienced HAI,with a HAI incidence of 9.17％.After PSM,all 65 patients in the HAI group were successfully matched.The length of hospital stay,total hospitalization expense,expenses of medication and hygiene product of patients in the HAI group were all higher than those in the non-HAI group,and differences were all statistically sig-nificant(all P＜0.001).Patients who experienced≥2 episodes of HAI had a higher economic burden than those who experienced only once(P＜0.05).HAI of bloodstream,abdomen,digestive system,and respiratory system significantly increased the economic burden of patients(all P＜0.05).Conclusion HAI in SAP patients can extend the length of hospital stay and increase economic burden of patients.Targeted infection prevention and control mea-sures should be formulated to reduce the incidence of HAI and save medical resources.

Tumor-associated macrophages(TAMs)are one of the key components of the tumor microenvironment(TME)in gastric cancer.Glucose metabolism reprogramming significantly impacts TAMs'polarization and immune functions,thereby regulating the onset and the progression of gastric cancer.This review summarizes glucose metabolism reprogramming in TAMs'polarization and explores its role in gastric cancer-related TAMs through aspects such as signaling regulation,transcription factors,and epigenetic modifications.This review aims to deepen the understanding of TAMs'role in gastric cancer progression and offer new perspectives for the immunotherapy in gastric cancer.

Depression, one of the most prevalent mental health disorders, has emerged as a critical focus in medical and neurobiological research, as well as a major challenge for global public health. The immune-inflammatory hypothesis has been confirmed to play a pivotal role in the pathogenesis and pathophysiology of depression, though its precise mechanisms remain to be fully elucidated. This article reviews the effects of key inflammatory factors, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and Toll-like receptors on depression. Additionally, it summarizes the effects of immune-inflammatory pathway invovled in the pathogenesis of depression, along with scientific clues related to inflammatory factors in this pathway. Findings from this review will provide new insights for antidepressant development and serve as a reference for evaluating the clinical efficacy of antidepressants.

Objective To explore the expression of peripheral blood Nod-like receptor protein 3(NLRP3)inflammasomes,serum caveolin-1(Cav-1),and sphingosine 1-phosphate receptor 1(S1P1)in children with Kawasaki disease(KD),and to elucidate their associations with coronary artery lesion(CAL).Methods A total of 223 children diagnosed with KD were recruited from our hospital between March 2023 and December 2024 and served as the KD study group.These children were classified into the CAL group(n=71)and the non-CAL group(n=152)based on their CAL status.Additionally,223 healthy children who underwent physical examinations at our hospital were selected as the healthy control group.Clinical data,levels of routine laboratory test indices,peripheral blood NLRP3 inflammasomes,serum Cav-1,and S1P1 were compared among the groups.Risk factors for CAL in children with KD were analyzed,and the diagnostic value of peripheral blood NLRP3 inflammasomes,serum Cav-1,and S1P1 levels for CAL in children with KD was evaluated.Results The levels of NLRP3,caspase-1,ASC in peripheral blood and messenger ribonucleic acid(mRNA)of serum Cav-1 were significantly higher in the KD study group than in the healthy control group(P<0.05).Conversely,the serum level of S1P1 was significantly lower in the KD study group compared to the healthy control group(P<0.05).In the CAL group,the levels of peripheral blood white blood cell count(WBC),NLRP3,caspase-1,ASC mRNA,serum C-reactive protein(CRP),and Cav-1 were all higher than those in the non-CAL group(P<0.05),while the serum level of S1P1 was lower than that in the non-CAL group(P<0.05).The levels of NLRP3,caspase-1,ASC mRNA in peripheral blood,along with serum Cav-1 and S1P1,were identified as independent risk factors for CAL in children with KD(P<0.05).The results of receiver operating characteristic(ROC)analysis indicated that the combined test of the levels of NLRP3,caspase-1,ASC mRNA in peripheral blood,serum Cav-1,and S1P1 for diagnosing CAL in children with KD had an area under the curve(AUC)value of 0.926.This value was significantly higher than that of each individual index(0.844,0.785,0.821,0.843,0.833,P<0.05).Conclusions The levels of NLRP3 inflamma-tory vesicles in peripheral blood and serum Cav-1 were highly expressed in children with KD,whereas the serum S1P1 was poorly expressed.These indices may be involved in the development process of CAL in children with KD.Moreover,the combination of these indices is more beneficial for the diagnosis of CAL in children with KD.

Objective:To explore patterns of traditional Chinese medicine (TCM) use among patients with inflammatory bowel disease (IBD) in Jiangsu Province, China from 2019 to 2023.Methods:Using data from the IBD health data platform of the National Healthcare Big Data (Eastern) Center, a retrospective cohort study was conducted. We performed descriptive analyses on hospitalised patients diagnosed with IBD between 2019 and 2023, who received TCM treatment.Results:The study included 11 095 case records from 4 760 patients, with TCM diagnoses primarily indicating diarrhoea and abdominal pain. Ulcerative colitis (UC) accounted for 4 782 hospitalizations (3 103 patients), while Crohn's disease (CD) accounted for 6 313 hospitalizations (1 657 patients). Patient demographics showed a trend towards younger age and a higher proportion of males. Treatment utilisation was highest in southern Jiangsu compared with the central and northern regions. In terms of disease burden, all treatment costs showed a downward trend. In terms of external TCM therapies, UC patients tend to prefer plasters and enemas, while CD patients are more inclined to use acupuncture. Regarding herbal medicine, licorice, white atractylodes, and white peony root are commonly used single herbs for IBD patients.Conclusions:The number of IBD patients treated with TCM in Jiangsu Province has steadily increased from 2019 to 2023. It is important to identify effective TCM treatment methods to reduce the burden of patients.

OBJECTIVE To investigate the role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.