Objective: To investigate the epidemiological characteristics of human brucellosis in Jiande City, Zhejiang Province from 2005 to 2024, so as to provide the evidence for strengthening the prevention and control of brucellosis. Methods: Data on brucellosis cases and surveillance in Jiande City from 2005 to 2024 were collected through the Chinese Disease Prevention and Control Information System, the annual brucellosis surveillance reports from the Jiande Center for Disease Control and Prevention, and the annual summaries of brucellosis prevention and control efforts. The epidemiological characteristics of human brucellosis were analyzed using a descriptive epidemiological method. Results: A total of 1 125 individuals were monitored in Jiande City from 2005 to 2024, with 18 seropositive cases identified and the seropositivity rate of 1.60%. The average annual seropositivity rate from 2015 to 2024 was 3.35%, which was significantly higher than that of 0.57% from 2005 to 2014 (P<0.05). There were 10 confirmed brucellosis cases and 8 asymptomatic infections, with no reported deaths. The peak incidence occurred between March and August. Among the 16 towns (streets) in Jiande City, 8 reported brucellosis cases. Of the brucellosis cases, 14 were male and 4 were female, with a male-to-female ratio of 3.5∶1. The majority of cases (13 cases) were aged between 40 and 60 years. Occupational exposure was identified in 16 cases, all of whom were infected through direct hand contact with the excreta, secretions, or animal products of infected sheep or cattle. The primary source of infection was sheep, followed by cattle. Five strains of Brucella were isolated and cultured, all identified as Brucella melitensis biovar 3. Conclusions The brucellosis epidemic in Jiande City remained at a sporadic and low prevalence level from 2005 to 2024, with an increasing trend observed from 2015 to 2024. Male occupational groups aged 40 to 60 years were the key population for brucellosis prevention and control, and sheep were the primary source of infection.

ObjectiveTo investigate the influence of entecavir （ETV） versus tenofovir alafenamide fumarate （TAF） on renal function in previously untreated patients with chronic hepatitis B （CHB）. MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023， and according to the antiviral drug used， they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data， propensity score matching （PSM） was used for matching and analysis at a ratio of 2∶1， and the two groups were compared in terms of estimated glomerular filtration rate （eGFR） and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48， the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function， and the receiver operating characteristic （ROC） curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function， and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching， there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group （all P>0.05）， with an eGFR level of 112.29±9.92 mL/min/1.73 m² in the ETV group and 114.72±12.15 mL/min/1.73 m² in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups， and compared with the TAF group at week 48， the ETV group had a significantly lower eGFR （106.42±14.12 mL/min/1.73 m² vs 112.25±13.44 mL/min/1.73 m²， t=-2.422， P=0.017） and a significantly higher incidence rate of abnormal renal function （17.00% vs 4.00%， χ²=5.092， P=0.024）. After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients， the univariate analysis showed that there were significant differences between the two groups in age （Z=-2.039， P=0.041）， treatment drug （ETV/TAF） （χ²=5.092， P=0.024）， and baseline eGFR level （t=4.023， P<0.001）， and the multivariate Logistic regression analysis showed that baseline eGFR （odds ratio ［OR］=0.896， 95% confidence interval ［CI］： 0.841 — 0.955， P<0.001） and treatment drug （OR=5.589， 95%CI： 1.136 — 27.492， P=0.034） were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients， with a cut-off value of 105.24 mL/min/1.73 m²， a sensitivity of 73.68%， and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m² had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m² （χ²=22.330， P<0.001）， and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group （χ²=4.961， P=0.026）. With the initiation of antiviral therapy， both the ETV group and the TAF group had a significant reduction in eGFR （F=5.259， P<0.001）， but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 （t=-2.422， P=0.017）； both the baseline eGFR≤105.24 mL/min/1.73 m² group and the baseline eGFR>105.24 mL/min/1.73 m² group had a significant reduction in eGFR （F=5.712， P<0.001）， and there was a significant difference in eGFR between the two groups at baseline and weeks 12， 24， 36， and 48 （t=-13.927， -9.780， -8.835， -9.489， and -8.953， all P<0.001）. ConclusionFor CHB patients initially treated with ETV or TAF， ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.

OBJECTIVE: To compare the clinical efficacy between thermo-electroacupuncture at yaosanzhen and oral celecoxib in the treatment of chronic lumbar muscle strain with cold dampness. METHODS: A total of 80 patients with chronic lumbar muscle strain of cold dampness were randomly divided into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 2 cases were excluded). The observation group was treated with thermo-electroacupuncture at yaosanzhen (bilateral Shenshu [BL23], Dachangshu [BL25], Weizhong [BL40]), disperse-dense wave was selected, with a pulse cycle of 0.08 s, current intensity of 1-3 mA, with needles heated to approximately 45 ℃, the duration was 25 min per session, once a day. The control group was given oral celecoxib capsules, once daily, 200 mg each time. Six sessions as one course, with a 1-day interval between courses, 2 courses were required in both groups. The TCM syndrome score, visual analogue scale (VAS) score, Oswestry disability index (ODI) score, and Japanese Orthopedic Association (JOA) score before and after treatment in both groups were compared. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), thromboxane B2 (TXB2) and C-reactive protein (CRP) were detected using ELISA method before and after treatment in both groups. The clinical efficacy was evaluated in both groups after treatment. RESULTS: After treatment, the TCM syndrome scores, VAS scores, ODI scores and serum levels of TNF-α, IL-6, TXB2, CRP in both groups were reduced compared with those before treatment (P<0.01), while the JOA scores were increased (P<0.01)；the TCM syndrome score, VAS score, ODI score and serum levels of TNF-α, IL-6, TXB2, CRP in the observation group were lower than those in the control group (P<0.01, P<0.05), and the JOA score was higher than that in the control group (P<0.01). The total effective rate of the observation group was 92.3% (36/39), which was superior to 78.9% (30/38) in the control group (P<0.05). CONCLUSION Thermo-electroacupuncture at yaosanzhen can alleviate pain symptom in patients with chronic lumbar muscle strain of cold dampness, regulate lumbar function, reduce the levels of inflammatory factors, and the therapeutic effect is superior to oral celecoxib.
Humans ; Male ; Female ; Middle Aged ; Adult ; Electroacupuncture ; Acupuncture Points ; Sprains and Strains/genetics* ; Cold Temperature ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-6/blood* ; Aged ; Treatment Outcome ; Young Adult ; C-Reactive Protein/metabolism* ; Chronic Disease/therapy* ; Lumbosacral Region/physiopathology*

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

With the rapid advancement of synthetic biology, CRISPR-Cas systems have emerged as a powerful tool for gene editing, demonstrating significant potential in various fields, including medicine, agriculture, and industrial biotechnology. This review comprehensively summarizes the significant progress in applying artificial intelligence (AI) technologies to the design, mining, and modification of CRISPR-Cas systems. AI technologies, especially machine learning, have revolutionized sgRNA design by analyzing high-throughput sequencing data, thereby improving the editing efficiency and predicting off-target effects with high accuracy. Furthermore, this paper explores the role of AI in sgRNA design and evaluation, highlighting its contributions to the annotation and mining of CRISPR arrays and Cas proteins, as well as its potential for modifying key proteins involved in gene editing. These advancements have not only improved the efficiency and precision of gene editing but also expanded the horizons of genome engineering, paving the way for intelligent and precise genome editing.
CRISPR-Cas Systems/genetics* ; Artificial Intelligence ; Gene Editing/methods* ; RNA, Guide, CRISPR-Cas Systems/genetics* ; Machine Learning ; Humans ; Genetic Engineering/methods* ; Synthetic Biology

Objective:To understand the medical care of patients with sporadic Creutzfeldt-Jakob disease in China and its relationship with survival time.Methods:A retrospective analysis was performed on data of 150 patients with sporadic Creutzfeldt-Jakob disease diagnosed by China′s Creutzfeldt-Jakob Disease Surveillance Network during the period of January 1, 2021 to December 31, 2022 in this study, and telephone follow-up with family members was used to obtain information of the patients′ care, treatment, and survival after diagnosis. Survival was estimated by life table method, median survival time and 95% confidence interval ( CI) were calculated by Kaplan-Meier method, log-rank method was used to compare the difference in survival time between different groups, and multifactorial analysis was performed by COX proportional risk regression model regarding the influencing factors on patients′ survival time. Results:The median survival time of 150 patients with sporadic Creutzfeldt-Jakob disease was 6 months, and the cumulative lifetime survival rates at 2, 6, 12, and 18 months were 62%, 39%, 22%, and 9%, respectively. The result of univariate analysis showed that the differences in survival time between groups with the presence or absence of cortical blindness in the first symptom, the presence or absence of respiratory support (oxygen therapy), the presence or absence of adjunctive medication, and the presence or absence of tube feeding (nasogastric) were meaningful ( P<0.1). Multifactorial COX regression analysis showed that the risk of death in patients without adjuvant medication was 1.429 times higher than that in patients with adjuvant medication (95.0% CI: 1.014-2.014), and the risk of death in patients without tube feeding (nasal feeding) was 1.479 times higher than that in patients with tube feeding (nasal feeding) (95% CI: 1.052-2.081). Conclusions:Whether or not adjuvant medication is administered and whether or not tube feeding (nasogastric) is used are factors that affect survival time in patients with sporadic Creutzfeldt-Jakob disease, and the administration of appropriate adjuvant medication and tube feeding (nasogastric) may contribute to prolonging survival time in patients with sporadic Creutzfeldt-Jakob disease.

Objective To investigate the survival time of patients diagnosed with sporadic Creutzfeldt-Jakob disease in China between 2020 and 2022 and explore the associated factors influencing survival.Methods A retrospective analysis was conducted on clinically diagnosed cases with complete information on sporadic Creutzfeldt-Jakob dis-ease diagnosed by the China Creutzfeldt-Jakob disease surveillance network from 2020 to 2022,baseline information of patients was obtained from the case files,telephone follow-up was used to obtain the treatment and survival status of the patients after the diagnosis,life-table method was used for estimating the survival rate,Kaplan-Meier method was used for calculating the median survival time and the 95％CI,Cox regression model was used for univariate and multivariate analyses were used to screen for factors influencing survival time.Results The median survival time of the 300 patients was 5 months(95％CI:4.165-5.835).Univariate analysis revealed that factors such as age at onset,regional distribution,presence of corticobasal or extrapyramidal symptoms as initial manifestations,number of initial symptoms,presence of corticobasal or extrapyramidal functional abnormalities,number of major clinical manifestations,presence of typical electroencephalogram findings,and use of nasal feeding during the course of the disease were potential factors influencing survival time(P＜0.1).Multivariate analysis showed that the risk of death in patients with onset age＞65 years was 1.350 times higher than in patients with onset age ≤65 years(P=0.021,95.0％CI:1.046-1.742).Patients without pyramidal or extrapyramidal dysfunction had a 0.674-fold lower risk of death compared to those with these symptoms(P=0.020,95.0％CI:0.483-0.939).Patients who did not receive nasal feeding had a 1.817-fold higher risk of death compared to those who did(P＜0.001,95.0％CI:1.406-2.349).Conclusion Age at onset,the presence of pyramidal or extrapyramidal functional abnormalities,and the use of nasal feeding during the disease course are factors influencing the survival time of pa-tients clinically diagnosed with sCJD.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. 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 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To investigate the clinical outcomes of lining repair during the reconstruction of nasal defects.Methods:From January 2010 to December 2022, our team treated 15 nasal defect patients aged between 18 and 62 years with an average age of 38, including 8 males and 7 females. The range of the defect was more than one subunit in all cases. And forehead pedicled flaps were chosen for repair. For nasal reconstruction, expander was implanted to expand the central forehead flap. The choice of support depended on the range of the defect, including rib-rib cartilage composite grafts, rib cartilage grafts and ear cartilage grafts. The repair of the lining was selected with the original skin, local nasolabial flapor forehead pedicled flap to repair the mucosal defect of the nose. Postoperative follow-up was conducted to observe the effects.Results:Among the 15 patients, 8 cases underwent rib-rib cartilage composite grafts. 3 cases had rib cartilage grafts, and 4 cases had ear cartilage grafts. All the flaps survived with 1 case experiencing infection. Postoperative follow-up for 0.5 to 2 years showed that the appearance of nasal defects in all 15 cases was significantly improved, with satisfactory results.Conclusions:The repair of nasal defect lining requires a comprehensive analysis based on the specific location, range of the defect, and the selection of the donor area in order to ultimately determine the surgical approach.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. 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 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.