Objective To explore the mechanism by which the sanguis draconis flavones(SDF)regulates the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway to mediate cell pyroptosis and improve cerebral ischemia-reperfusion injury(CIRI)in rats.Methods The experimental rats were randomly divided into the control group(Ctrl),the CIRI group,the low-dose SDF group(SDF-L),the high-dose SDF group(SDF-H),and the SDF-H+ROS/TXNIP pathway activator,trimethylamine oxide(TMAO)group(SDF-H+TMAO).Among them,except for the control group,the remaining rats all needed to establish the CIRI rat model by the modified suture method.Zea Longa scoring was performed on rats from each group.ELISA was used to detect the levels of serum inflammatory factors interleukin(IL)-1β,IL-18 and oxidative stress-related factors superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px).Flow cytometry was used to measure the ROS levels.Cerebral edema was detected.Cerebral infarction was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining was used to detect the pathological changes of brain tissue.Immunohistochemistry was used to detect the expression of pyrolytic effector protein dermolin D(GSDMD).Western blotting was used to detect the expression of proteins related to the ROS/TXNIP pathway.Results Compared with the control group,a large area of cerebral infarctions were observed in the brain tissue of the CIRI group,accompanied by mild hemorrhage and obvious infiltration of inflammatory cells.Neuronal cells underwent degeneration and necrosis,with sparse and disordered arrangement.The phenomena of nuclear condensation and nucleolus lysis were obvious.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-related punctate protein(ASC),and Caspase-1 increased,while the activities of SOD and GSH-Px decreased(P＜0.05).Compared with the CIRI group,the pathological damage of brain tissues in the SDF-L group and the SDF-H group was significantly improved.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,NLRP3,ASC,and Caspase-1 decreased.The activities of SOD and GSH-Px increased(P＜0.05);TMAO treatment partially reversed the improvement effect of SDF on CIRI in rats.Conclusion SDF ameliorates cerebral CIRI in rats by inhibiting ROS/TXNIP pathway-mediated pyroptosis.

Objective To evaluate the effects of Modified Wendan Decoction combined with Intestinal Regulation and Mind-Regulating Acupuncture on cognitive,social,and self-care abilities in children with autism spectrum disorder(ASD).Methods A total of 100 children diagnosed with ASD at Anhui Children's Hospital(inpatient and outpatient)from February 2023 to March 2024 were enrolled.The participants were divided into an observation group(n=50)and a control group(n=50)using a random number table.The control group received conventional rehabilitation training and Intestinal Regulation and Mind-Regulating Acupuncture,while the observation group received additional Modified Wendan Decoction.Both groups underwent a 2-month treatment period.Post-treatment assessments included clinical efficacy,changes in Childhood Autism Rating Scale(CARS)scores,Autism Behavior Checklist(ABC)scores,and Autism Treatment Evaluation Checklist(ATEC)scores were observed.Additionally,Social Responsiveness Scale(SRS)and Infant-Junior Middle School Student Social Life Abilities Scale(S-M)scores were compared between groups.Results(1)During the study,1 case was lost to follow-up in the observation group and 2 in the control group,leaving 49 and 48 cases for final analysis,respectively.(2)After treatment,both groups showed significant improvements in CARS,ABC,and ATEC scores(P＜0.05),with the observation group demonstrating superior improvements compared to the control group,the difference being statistically significant(P＜0.05).(3)Similarly,both groups exhibited marked improvements in SRS and S-M scores(P＜0.05),with the observation group outperforming the control group,the difference being statistically significant(P＜0.05).(4)The total effective rate was 81.63％(40/49)in the observation group versus 56.25％(27/48)in the control group,indicating significantly better efficacy in the observation group,the difference being statistically significant(P＜0.05).Conclusion Modified Wendan Decoction combined with Intestinal Regulation and Mind-Regulating Acupuncture significantly improves clinical symptoms and enhances cognitive,social,and self-care abilities in children with ASD,demonstrating notable therapeutic efficacy.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Objective To explore the relationship between dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and clinical pathological features of invasive breast cancer and lymphovascular invasion(LVI).Methods Imaging and clinical pathological data were retrospectively collected from 508 patients with invasive breast cancer who underwent breast DCE-MRI at the First Medical Center of Chinese PLA General Hospital from January 2019 to August 2021.Patients were divided into the LVI-positive(LVI+)group(n=79)and LVI-negative(LVI-)group(n=429)based on postoperative pathological results.Univariate and multivariate logistic regression analyses were used to identify risk factors for LVI.Results Compared with LVI-group,LVI+group had a higher proportion of patients aged<45 years(44.3%vs.27.0%,P=0.002),non-mass-like enhancement(NME)(31.7%vs.17.7%,P=0.004),Ki-67 expression rate(40.0%vs.30.0%,P<0.001),high Ki-67 expression(94.9%vs.78.1%,P=0.001),Luminal B subtype(76.0%vs.60.1%,P=0.008),and positive axillary lymph nodes rate(72.2%vs.31.5%,P<0.001),while the proportion of Luminal A subtype was lower(2.5%vs.21.5%,P<0.001).Univariate and multivariate logistic regression analyses showed that age≥45 years(OR=0.468,95%CI 0.280-0.783,P=0.004)was an independent protective factor for LVI,while NME(OR=1.987,95%CI 1.126-3.444,P=0.016)was an independent risk factor.Compared with Luminal A subtype,patients with Luminal B subtype(OR=10.482,95%CI 3.164-64.923,P=0.001),HER-2 overexpression subtype(OR=11.571,95%CI 2.755-79.341,P=0.003)and triple-negative subtypes(OR=8.433,95%CI 1.985-57.908,P=0.009)had a higher risk of LVI.Conclusions Age≥45 years is an independent protective factor for LVI,while NME is an independent risk factor.Among molecular subtypes,patients with Luminal B,HER-2 overexpression and triple-negative subtypes have a higher risk of LVI compared with the Luminal A subtype.

Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.

Objective To observe the difference of bone micro-structure in different regions of proximal femur,micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers.Micro-CT scanning was used to measure the trabecular thickness(Tb.Th),trabecular number(Tb.N),trabecular space(Tb.Sp),connectivity(Conn)and bone mineral density(BMD)and other parameters in 7 regions of proximal femur,including proximal pressure trabecular(PPT),distal pressure trabecular(DPT),femoral head-neck junction(FHNJ),head and neck of femoral neck(HNFN),the base of femoral neck(BPFN),intertrochanteric line(IL)and greater trochanter(GT).Results The bone mineral density of IL and GT were higher than those of BPFN,FHNJ,DPT and PPT.The trabecular thickness of GT was the largest,followed by IL,BPFN and HNFN,and the smallest was FHNJ,DPT and PPT.The trabecular space of IL was larger than that of GT,and the data of both were larger than those of other parts,among which DPT and PPT were the smallest.The trabecular number of IL and GT were the smallest,BPFN,HNFN and FHNJ were larger,and DPT was the largest.The volume fraction of IL was the smallest,BPFN and HNFN were larger,DPT and PPT were the largest.Conclusion The bone density,trabecular thickness,bone volume,and total volume of GT and IL in the proximal femur of elderly patients are all relatively large,so the reason for the high incidence of fractures is not due to weak internal bone microstructure;The bone density,trabecular thickness,and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small.If it is necessary to perform core decompression for prosthesis filling at this location,the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.

Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

This report summarized and analyzed the clinical data of 3 patients with food-borne botulism admitted to our department. One case was sporadic, while the other two involved family members living together. All patients initially presented with blurred vision, ptosis, and dysphagia, and the disease progressed rapidly. During the course of the disease, all three cases developed respiratory failure; one patient received non-invasive ventilatory support, whereas the other two required invasive ventilator assisted ventilation. The serum toxin tests of the 3 patients were all positive for botulinum toxin type A. Sporadic food-borne botulism shares similar early symptoms and signs to myasthenia gravis and Guillain-Barre syndrome, and requires careful differential diagnosis. Botulinum antitoxin serum is the only effective treatment, and empirical antitoxin administration can be initiated immediately upon suspicion of botulism. Early detection and timely specific treatment are critical for improving patient outcomes.

Objective:To explore the clinical characteristics and prognosis risk factors of aggressive NK-cell leukemia(ANKL).Methods:The clinical and laboratory data of 34 patients with ANKL and 15 patients with chronic lymphoproliferative disorders of NK cells(CLPD-NK)admitted to the First Affiliated Hospital of Zhengzhou University from September 2019 to December 2024 were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,and the Cox proportional hazards regression model was used to analyze prognostic factors.Results:Compared with CLPD-NK patients,ANKL patients had a younger median age of onset,a higher proportion patients with EBV-DNA≥500 copies/ml,hepatosplenomegaly and hemophagocytic syndrome.They also presented with a higher peak of fever,a shorter median survival time,lower WBC count,PLT count,ALB and Fib values,while having higher LDH,AST,TG,ferritin,CRP and PCT levels.There were statistically significant differences in the morphology and expression of HLA-DR,CD56,CD57,CD16 and CD158 on abnormall cells between ANKL patients and CLPD-NK patients.Multivariate survival analysis revealed that combined with asparaginase treatment could improve patients' survival,and CRP≥ 15 mg/L and Fib＜2.0 g/L were independent risk factors affecting the overall survival of patients with ANKL.Conclusion:The differences in clinical features and laboratory tests between patients with ANKL and CLPD-NK aid in the diagnosis of ANKL.CRP and Fib levels can be used to predict the prognosis of patients,and combined asparaginase therapy can enhance the overall survival of patients.