Objective:To investigate the effects of melatonin(MT)on spinal cord ischemia reperfusion injury(SCIRI)and its possible mechanisms in rats.Methods:Forty-two 6-week-old male Sprague Dawley rats were selected for the study and randomly divided into three groups:① Sham group(Sham group,n=14);② model group(model/SCIRI group,n=14);and ③ treatment group(MT group,n=14).Neurological function analysis was used to assess the motor conditions of rats in each group.Nissl staining and hematoxylin eosin(HE)staining were used to observe the number and morphology of neurons in each group,and TUNEL staining was used to evaluate the occurrence of apoptosis of neurons in each group.The expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),gasdermin D(GSDMD),the N-terminal fragment of gasdermin D(GSDMD-N),and cysteine proteinase 1(caspase-1)were evaluated using immunofluorescence,immunohistochemistry staining,and Western blot analysis.Results:Compared with the sham operation group,the neurological function score of the model group was significantly decreased,while the neurological function score of the treatment group was higher than that of the model group(P＜0.05).The model group had fewer Nissl corpuscles compared with that in the sham operation group and abnormal neuronal morphology(P＜0.05).Compared with the model group,the treatment group had a rise in the number of Nissl corpuscles and restored neuronal morphology(P＜0.05).Compared with the Sham group,the number of apoptotic neurons increased in the model group,and the protein expression levels of NLRP3,ASC,GSDMD,and caspase-1 increased(P＜0.05).Compared with the model group,The number of apoptotic neurons and the protein expressions of NLRP3,ASC,GSDMD and caspase-1 in the treatment group were significantly decreased(P＜0.05).Conclusions:MT may alleviate spinal cord ischemia-reperfusion injury by inhibiting pyroptosis in neurons.

Objective To develop a rehabilitation exercise program for the patients with osteoporotic vertebral compression fractures.Methods An online search was performed across both Chinese and English databases and websites to retrieve literature on rehabilitation exercises and related therapeutic measures for patients with osteoporotic vertebral compression fractures.Two researchers independently screened the retrieved literature,evaluated the quality,and extracted relevant evidence.Semi-structured interviews were conducted among 15 patients at various rehabilitation phases about the requirements of rehabilitation.A preliminary exercise program was developed and verified for the validity and feasibility using Delphi method.Results A rehabilitation exercise program was formulated.The program included five periods of preoperative period,bedridden period after surgery,ambulation period(1 week after surgery),weeks 2-8 after surgery and weeks 9-12 after surgery covering six domains of exercise type,exercise items,exercise duration,exercise frequency,exercise intensity and exercise safety.The response rate and effective rate over the two rounds of expert consultation were both 100.00%,with an authority coefficient of 0.94.The Kendall's W coefficients for secondary indicators in the two rounds of expert consultation were 0.184 and 0.334,respectively(both P<0.001).Conclusion The exercise program developed in this study for the patients with osteoporotic vertebral compression fractures is scientifically reliable and reasonable.The two features of continuity and staged characteristics in rehabilitation process are fully considered,thereby it offers a guidance for clinical healthcare professionals as well as the patients in development of practical and effective rehabilitation exercise plans.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Objective To analyze the epidemiological characteristics of human papillomavirus(HPV)infection in women in the Zhongguancun area of Beijing,and to evaluate the infection rates and genotype distribution between different populations and age groups.Methods A retrospective analysis was conducted on HPV genotyping results of 13,105 women who visited the gynecology outpatient department or underwent routine health check-ups at Zhongguancun Hospital from March 2019 to April 2024.High-risk HPV genotypes(15 types)were detected using a fluorescence PCR assay.Positive cases were classified as single,dual or multiple(≥3)infections based on the number of genotypes.Subjects were stratified into six age groups(≤30,31-40,41-50,51-60,61-70,and≥71 years),and the characteristics of infection by type and age group were analyzed.Results The overall HPV positivity rate was 10.78%(1,413/13,105),with a significantly higher rate in the outpatient group than that in the health check-up group(16.36%vs.6.06%,P<0.01).The three most prevalent genotypes were HPV52(18.83%),HPV58(13.85%),and HPV16(11.28%).Single infections accounted for 79.19%of cases,dual infections for 15.93%and multiple infections for 4.88%.Age distribution showed a U-shaped pattern,with higher infection rate in women aged≤30 years(15.06%)and 61-70 years(13.19%),and the lowest rate in the≥71 years(8.09%).Notably,women aged≤30 years had the highest proportion of multiple infections(31.72%).Conclusion These findings provide a basis for cervical cancer screening strategies,HPV vaccination promotion and individualized prevention of cervical cancer in this region.

Objective To investigate the clinical efficacy of continuous irrigating mode of endoscopic ear sur-gery(CIM-EES)utilizing tragus cartilage-perichondrium without tympanomeatal flap elevation in repairing tympanic membrane perforation.Methods The date of 70 patients(70 ears)who underwent tympanic membrane repair under ear endoscopy from June 2020 to August 2023 were randomly selected and analyzed.They were divided into two groups according to the time of operation:CIM-EES group(observation group)of 44 cases(44 ears)and a conven-tional surgery group(control group)of 26 cases(26 ears).Both groups were repaired with tympanic membrane per-foration using the method of implanting tragus cartilage-perichondrium grafts under endoscope without tympa-nomeatal flap elevation.After 6 months of postoperative follow-up,two groups were compared in terms of operation time,frequency of the endoscopic lens scrubbing,postoperative healing rate,and hearing improvement outcomes.Results The average operation time of the observation group and the control group was 37.50±4.81 minutes and 50.31±8.21 minutes respectively,and the average number of scrubbing the endoscope was 6.77±1.51 and 35.54±7.13 respectively,there was statistical difference significance between the two groups(P＜0.01).All patients in the observation group were successfully repaired in the first stage,with the healing rate of 100％(44/44),and one patient in the control group had a postoperative small perforation that healed after secondary repair with the healing rate of 96.15％(25/26).There was no statistically significant difference between the two groups.The average 6 months postoperative air conduction threshold and air-bone conduction threshold of 0.5-4 kHz in the two groups improved compared to preoperative results(P＜0.01),with no statistically significant difference between the two groups(P＞0.05).Conclusion Endoscopic myringoplasty without tympanomeatal flap elevation under continuous irrigating mode has the advantages of high healing rate,short operation time,simple surgical operation,few post operation complications and good hearing improvement.

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

Alzheimer's disease (AD) is the commonest neurodegenerative disease that causes memory decline, cognitive dysfunction and behavior disorders in the aged people. Primary pathological hallmarks of AD include amyloid-β (Aβ), neurofibrillary tangles (NFTs), gliosis, and neuronal loss. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have important physiological functions, especially in aspects of controlling the resting membrane potential, pacemaker activity, memory formation, sleep and arousal. This article reviews the structure, distribution, regulation of HCN channels and the role of HCN channels in the pathological mechanisms of AD, aiming to provide drug therapeutic targets for the prevention and treatment of AD.
Humans ; Alzheimer Disease/physiopathology* ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/physiology* ; Animals ; Amyloid beta-Peptides/metabolism*

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To establish a model for the combined detection of serum copeptin and inflammatory markers in acute stroke (AS), and to explore the value of copeptin and inflammatory marker detection in the clinical diagnosis and prognosis assessment of AS.Methods:A total of 75 patients were diagnosed with acute ischemic stroke (AIS) [46 males, age (64.1±11.7) years] and 45 patients with acute intracerebral hemorrhage (ICH) [28 males, age (61.0±13.9) years] who were admitted to the First Affiliated Hospital of Hunan University of Chinese Medicine through the emergency department from January 1 to July 31, 2024, were included as the observation group. Meanwhile, 60 healthy individuals [39 males, age (64.4±8.2) years] were selected as the control group (HC). The differences in serum copeptin levels and inflammatory markers among different groups were compared. ROC curves were drawn to analyze the value of copeptin and inflammatory markers in the clinical diagnosis and prognosis assessment of AIS. The Kaplan-Meier method was used to draw survival curves to analyze the in-hospital survival rates of patients in different groups. Cox regression analysis was conducted to identify the risk factors affecting the prognosis of AIS patients.Results:The level of copeptin was significantly elevated in AS, with the results showing ICH>AIS>HC ( H=100.11, P<0.001). Copeptin demonstrated the highest efficacy in the early diagnosis of AIS and ICH (AUC=0.893, sensitivity 89.3%, specificity 75.0%; AUC=0.986, sensitivity 95.6%, specificity 93.3%) and the assessment of prognosis (AUC=0.997, sensitivity 100%, specificity 96.8%; AUC=0.907, sensitivity 86.7%, specificity 86.7%), outperforming other single indicators. The combined detection of copeptin with the neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SIIRI) was the best combination for the early diagnosis of AIS and ICH (AUC=0.937, sensitivity 77.3%, specificity 98.3%; AUC=0.989, sensitivity 95.6%, specificity 95.0%) and for the assessment of prognosis (AUC=0.996, sensitivity 100%, specificity 96.8%; AUC=0.944, sensitivity 86.7%, specificity 90.0%). Kaplan-Meier survival curves showed that AIS patients in the low-value group of copeptin and NLR had a higher survival rate during hospitalization than those in the high-value group ( HR 54.46, 7.608, P<0.01, respectively), and ICH patients in the low-value group of copeptin, SIIRI, SIRI, and SII had a higher survival rate during hospitalization than those in the high-value group ( HR 12.67, 7.923, 3.567, 5.925, P<0.05); Cox regression showed that copeptin, NLR, NIHSS, and mRS were independent risk factors affecting the prognosis of patients with AIS ( HR 1.421, 1.368, 1.158, and 1.188, respectively, P<0.05), copeptin and SIIRI were independent risk factors affecting the prognosis of ICH ( HR 1.308, 1.113, P<0.05), and GCS was a protective factor affecting ICH prognosis ( HR=0.741, P<0.05). Conclusion:Copeptin and inflammatory indicators can reflect the severity of different subtypes of stroke. The single or combined detection shows good value in the clinical application of AS. The combination of copeptin-NLR and copeptin-SIIRI is respectively the best comprehensive biomarker combination for the early diagnosis and prognosis assessment of AIS and ICH.