OBJECTIVE To investigate the effects of alirocumab combined with atorvastatin on clinical efficacy and safety of patients with acute coronary syndrome （ACS） who underwent percutaneous coronary intervention （PCI）. METHODS A total of 207 patients with ACS who underwent PCI in our hospital from January 2021 to December 2023 were randomly divided into alirocumab group， ezetimibe group and control group， with 69 cases in each group. All patients received routine thrombosis prevention and antihypertensive treatment after PCI. On this basis， patients in the control group were treated with atorvastatin （20 mg/time， once a day）； patients in the ezetimibe group were treated with ezetimibe （10 mg/time， once a day） + atorvastatin （20 mg/time， once a day）； patients in the alirocumab group were treated with alirocumab （75 mg/time， once every 2 weeks） + atorvastatin （20 mg/time， once a day）. All patients in the three groups were treated for 8 weeks and followed up for another 6 months after treatment. The levels of cardiac function and lipid metabolism indices before and after treatment， as well as the occurrence of major adverse cardiovascular event （MACE） and other adverse drug reaction （ADR） during the follow-up period were compared among the three groups. RESULTS After treatment for 8 weeks， the levels of cardiac function and lipid metabolism indices in the three groups were significantly improved compared with those before treatment （P＜0.05）. Compared with the control group and ezetimibe group， the left ventricular ejection fraction in the alirocumab group was significantly increased， and the left ventricular end-diastolic diameter （LVEDD） was significantly shortened （P＜0.05）. Compared with control group， LVEDD of ezetimibe group was significantly shortened （P＜0.05）， the levels of total cholesterol， triglyceride and low-density lipoprotein cholesterol in the alirocumab group and ezetimibe group were significantly decreased （P＜0.05）. During the follow-up period， there was no significant difference in the total incidence of MACE and the total incidence of other ADR such as headache and abdominal pain among the three groups （P＞0.05）. CONCLUSIONS Alirocumab combined with atorvastatin can significantly improve cardiac function and regulate lipid metabolism indices in patients with ACS after PCI without increasing the risk of MACE or other ADR.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Background::Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods::The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 +) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results::The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10-unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. Conclusions::This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.

Aim To investigate the effect and role of neuronal restriction silencing factor(REST/NRSF)in epilepsy disorder.Methods Immunohistochemistry,immunofluorescence,Western blot and qPCR tech-niques were used to detect REST/NRSF expression levels in hippocampal tissues of mice induced by kainic acid and human brain tissue.Viral injections,EEG re-cordings and behavioral methods were used to test the effects on epileptic mice after knockdown and overex-pression of REST/NRSF in the hippocampal CA1 re-gion,respectively.Results The positive rate of REST/NRSF in the lesions of epileptic patients was significantly higher compared with that in the control group.The levels of REST/NRSF protein and mRNA in the CA1 region of the hippocampus of mice in the KA model group were significantly higher.Kv7.2 and Kv7.3 potassium channel mRNA expression levels were significantly down-regulated.Significant up-regu-lation of REST/NRSF expression levels was observed in mouse hippocampus after NMDA injection.Knock-down of REST/NRSF in the CA1 region of hippocam-pus significantly elevated the expression levels of Kv7.2 and Kv7.3 potassium channel mRNAs.The fre-quency of EEG spiking and sharp-wave issuance and epileptic seizure grade were significantly lower.Over-expression of REST/NRSF in the CA1 region of hippo-campus significantly reduced the mRNA expression lev-els of Kv7.2 and Kv7.3 potassium channels.The fre-quency of EEG spiking and sharp-wave issuance was significantly higher and epileptic symptoms were exac-erbated.Conclusion REST/NRSF in mouse hipp-ocampal brain regions is involved in epileptic disease development through transcriptional regulation of Kv7.2 and Kv7.3 potassium channels.

Objective To compare the efficacy of blood letting under pain point touch and ultrasound-guided puncture de-compression in the treatment of acute supraspinatus muscle calcifying tendinitis.Methods From January 2020 to January 2023,45 patients with acute supraspinatus muscle calcifying tendinitis were selected and divided into treatment group and control group.In the treatment group,a total of 22 patients were treated with ultrasound-guided puncture decompression,in-cluding 16 females and 6 males,aged from 20 to 64 years old(39.31±5.80)years old,11 on the left shoulder and 11 on the right shoulder.In the control group,there were 23 cases,including 15 females and 8 males,aged from 19 to 66 years old(40.67±6.13)years old,12 on the left shoulder and 13 on the right shoulder.The treatment was treated with pain point touch bloodletting therapy.The visual analog scale(VAS)pain score,University of California,Los Angeles(UCLA)shoulder system score and shoulder Constant-Murley score were used to evaluate the therapeutic effect before treatment,1 weeks,1 month and 3 months after treatment,respectively.Results One patient in the control group gave up follow-up for personal reasons after 1 week of treatment,and the other 44 patients completed all follow-up.Six months after treatment,there were no recurrence cases in both groups.After statistical analysis,VAS pain score,UCLA score and Constant-Murley score of the treatment group and the control group were significantly different from those before treatment(P＜0.05),and the improvement was more obvious in the treatment group.There was no statistical significance between the two groups(P＞0.05).Conclusion Bloodletting under pain point touch and ultrasound-guided puncture decompression are effective in the treatment of acute calcific supraspinatus tendinitis,with simple operation and low cost,which can effectively reduce local pain and effectively improve shoulder joint function.Primary hospitals can selectively operate treatment according to their own conditions.

Enteropathogenic Escherichia coli(EPEC),a zoonotic foodborne pathogen,can induce severe and prolonged di-arrhea,thus substantially affecting global public health safety.To understand the pathogenicity of EPEC and its potential risk to human health,this study investigated the antimicrobial resistance and genome-wide characteristics of EPEC originating from ducks.After identification of EPEC with the plate method and PCR,antimicrobial susceptibility of the isolates was examined with the microbroth dilution method.In addition,analyses of serotype,sequence type(ST),and plasmid incompatibility groups were conducted with whole-genome sequencing(WGS)and bioinformatic methods.Ten EPEC isolates were identified,including serotypes O71∶H40 and O3∶H21.All EPEC strains exhibited multiple drug resistance.The highest proportion of resistance(100％)was observed to ciprofloxacin,streptomycin,tetracycline,and polymyxin B.In contrast,the isolates showed susceptibility to cefoxitin,amikacin,and imipenem.Furthermore,all strains carried the tetracycline resistance gene tet(A)and extended-spectrum β-lactamase(ESBL)resistance genes,including blaOXA-10,blaTEM-1A,and blaTEM-1B.Various virulence genes,associated primarily with the secretory system,were de-tected in the isolates.However,no bf p genes or per ARC genes were identified,thus indicating that the EPEC isolates were atypical EPEC(aEPEC).The results demonstrated the presence of multiple antimicrobial resistance,multiple resistance and viru-lence genes,and various plasmid incompatibility groups,thus in-dicating potential pathogenicity to humans.Strengthened monitoring of duck-derived EPEC is crucial to effectively control the spread of the pathogen and safeguard public health.

Objective:To explore the potential causal relationship between gut microbiota and teratozoospermia.Methods:We searched the database of Genome-Wide Association Study(GWAS)for gut microbiota-and teratozoospermia-related data.We used gut microbiota as an exposure factor,determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance,and derived the outcome variables from the European data on teratozoospermia,with a sample size of 85 716,including 915 cases and 209 006 controls.Using inverse-variance weighting(IVW),MR-Egger regression and the weighted median estimator(WME),we performed two-sample Mendelian randomization(MR)analysis on the retrieved data,and estimated the causal relationship between gut microbiota and teratozoospermia based on the β value.Results:Two-sample MR analysis indicated that the class Erysipelotrichia,family Erysipelotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridialesm and order Erysipelotrichales were causally related with the increased risk,while the family Porphyromonadaceae with the decreased risk of teratozoospermia.Conclusion:The class Erysipelotrichia,family Erysipe-lotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridia-lesm and order Erysipelotrichales are one of the causes of teratozoospermia,related to the increased risk of the condition,while the family Porphyromonadaceae has a protective effect on sperm morphology,reducing the risk of teratozoospermia.

Alzheimer's disease (AD) is a common and highly disabling irreversible degenerative disease of the central nervous system, with characteristics as progressive cognitive impairment, memory loss, and behavioral disturbances. Cognitive impairment in AD, being closely associated with amyloid beta-protein (Aβ) deposition, Tau hyperphosphorylation and neuroinflammation, affects the quality of life of patients. Currently, the exact cause of AD remains unclear, and effective treatment options still lacks. In recent years, stem cell-derived exosomes have garnered widespread attention due to their unique biological properties and crucial role in intercellular communication. These exosomes can carry various bioactive molecules, such as proteins, lipids, and RNA, playing significant roles in central nervous system degenerative diseases. Therefore, this article primarily describes the biogenesis, biological characteristics, and advantages of stem cell-derived exosomes, and summarizes their current applications and future prospects in cognitive impairment in AD, aiming to provide new insights for AD treatment.

Objective:To explore the molecular mechanism of clinical bleeding in a family with hereditary coagulation factor Ⅺ (FⅪ) deficiency caused by a novel mutation of the coagulation factor Ⅺ (FⅪ) gene.Methods:A male proband with hereditary coagulation factor XI deficiency who was admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University due to "adenoid hypertrophy" on February 23, 2023 and his family members (5 people in 3 generations) were selected as research subjects. The clinical data of the proband and family members were collected; the relevant coagulation indexes of all members were tested; those with abnormal coagulation indexes (prolonged activated partial thromboplastin time (APTT), normal thrombin time (PT) and fibrinogen (Fib)) were selected for APTT correction experiment; those with corrected Rosner index (RI) less than 10% were selected to detect FⅪ activity (FⅪ:C) by one-step method, FⅪ antigen (FⅪ:Ag) by ELISA method, and whole exon sequence by Illumina sequencing method. New mutation sites were rated according to the American College of Medical Genetics and Genomics (ACMG) related variation rating guidelines, and bioinformatics software was used to predict the impact of new mutations on protein structure and function.Results:The APTT of the proband, his father and his daughter were all prolonged and their RI were all less than 10%. Further tests revealed that FⅪ:C and FⅪ:Ag of the three were all decreased. Illumina sequencing revealed a new frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ of the three people, and a missense mutation c.G1253T (p.Gly418Val) in exon 11 of FⅪ of the proband′s father. ACMG rated the new mutation as pathogenic, and c.G1253T was a reported possible pathogenic mutation.Conclusion:The heterozygous frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ may be the main molecular mechanism of the disease in this family.

Objective To evaluate the feasibility of emergency percutaneous coronary intervention(PCI)with extracorporeal membrane oxygenation(ECMO)support in critically ill patients with acute myocardial infarction(AMI)and cardiogenic shock(CS).Methods Retrospective analysis of clinical data of AMI combined with CS patients admitted to the department of emergency of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking,coronary heart disease,arrhythmia,diabetes,hypertension,hyperlipidemia,cerebrovascular disease);acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,highest vasoactive-inotropic score(VIS)within 24 hours of admission,the worst auxiliary examination values within 24 hours after admission:blood lactic acid(Lac),arterial partial pressure of oxygen(PaO2),cardiac troponin I(cTnI),alanine aminotransferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium,left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)],presence of malignant arrhythmia or cardiac arrest during emergency PCI,completion of PCI,and the 30-day prognosis,etc.Patients were divided into an ECMO group and a non-ECMO group based on whether ECMO was applied,to analyze differences in the above indicators between the two groups.Results There were no statistically significant differences between the ECMO group and the non-ECMO group in terms of gender,age,BMI,past history,APACHEⅡ,VIS and the worst auxiliary examination value within 24 hours after admission.The incidence of malignant arrhythmia or cardiac arrest events and 30-day mortality rate during emergency PCI in the ECMO group were significantly lower than those in the non-ECMO group[the incidence of malignant arrhythmia or cardiac arrest during emergency PCI was 17.9％(7/39)vs.45.0％(9/20),and the 30-day mortality was 46.2％(18/39)vs.75.0％(15/20),both P<0.05].The completion rate of PCI in the ECMO group was significantly higher than that in the non-ECMO group[100.0％(39/39)vs.80.0％(16/20),P<0.05].Conclusions For critically ill patients with AMI combined with CS,ECMO support can reduce the risk of malignant arrhythmia or cardiac arrest during emergency PCI,increase the completion rate of PCI,and reduce the 30-day mortality.With the support of the ECMO team,ECMO support emergency PCI is feasible.