Metabolic associated fatty liver disease （MAFLD） is a common chronic liver disease worldwide， and timely and precise intervention can delay disease progression and significantly reduce the risk of serious complications such as liver fibrosis， liver cirrhosis， and liver cancer. Although traditional liver biopsy combined with metabolic markers is the gold standard， it may cause complications such as pain and bleeding as an invasive examination， which has promoted scientific research to shift its focus to the construction of noninvasive assessment systems. In recent years， noninvasive diagnostic technologies based on multi-dimensional detection strategies have been continuously updated， including serological models， imaging techniques， and clinical algorithms. This article systematically reviews the screening methods for MAFLD during the fibrotic stages F1—F3， especially deep learning models based on artificial intelligence， in order to provide ideas for the early screening of MAFLD， as well as a scientific reference for optimizing disease management strategies.

Male factors contribute to 50% of infertility cases, with 20%-30% of cases being solely attributed to male infertility. Helicase for meiosis 1 ( HFM1 ) plays a crucial role in ensuring proper crossover formation and synapsis of homologous chromosomes during meiosis, an essential process in gametogenesis. HFM1 gene mutations are associated with male infertility, particularly in cases of non-obstructive azoospermia and severe oligozoospermia. However, the effects of intracytoplasmic sperm injection (ICSI) in HFM1 -related infertility cases remain inadequately explored. This study identified novel biallelic HFM1 variants through whole-exome sequencing (WES) in a Chinese patient with severe oligozoospermia, which was confirmed by Sanger sequencing. The pathogenicity of these variants was assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting, which revealed a significant reduction in HFM1 mRNA and protein levels in spermatozoa compared to those in a healthy control. Transmission electron microscopy revealed morphological abnormalities in sperm cells, including defects in the head and flagellum. Despite these abnormalities, ICSI treatment resulted in a favorable fertility outcome for the patient, indicating that assisted reproductive techniques (ART) can be effective in managing HFM1 -related male infertility. These findings offer valuable insights into the management of such cases.
Humans ; Male ; Sperm Injections, Intracytoplasmic ; Oligospermia/therapy* ; Adult ; Spermatozoa/ultrastructure* ; Exome Sequencing ; Mutation

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

The aim of this study is to explore the immunogenicity of African swine fever virus p37 recombinant protein in mice.C57BL/6J mice were immunized subcutaneously in the abdomen using p37 recombinant protein as antigen.The second immunization was performed 21 d after the first immunization.Serum-specific antibody levels were detected by ELISA;serum cytokine levels were detected using a multifactor assay technique;mice splenic lymphocytes were isolated 7 d after sec-ondary immunization,and the number of splenic lymphocytes secreting IFN-γ after recombinant protein stimulation was detected by ELISpot;and the ratio of CD4+T cells to CD8+T cells was detected by flow cytometry.The results of indirect ELISA showed that p37 recombinant protein could stimulate mice to produce high levels of specific antibodies;ELISpot showed that p37 recom-binant protein could significantly stimulate splenic lymphocytes to produce IFN-γ(P＜0.001)and activate cellular immune responses;the results of flow cytometry showed that it could signifi-cantly stimulate the differentiation of T-lymphocytes to CD4+T-lymphocytes(P＜0.001).In ad-dition,serum levels of IL-2,IL-4,IFN-γ,and TNF-α immune-related cytokines were significantly higher after the second immunization.Immunization of mice with p37 recombinant protein induced strong humoral and cellular immune responses with good immunogenicity,providing reference for the subsequent epitope identification and functional study of p37 protein and the antigen screening of ASF mRNA vaccine.

In order to establish a highly efficient,convenient,and effective circular RNA(circRNA)vaccine preparation system,enhanced green fluorescent protein(EGFP)circRNA was constructed using permuted intron exon(PIE)strategy based on type Ⅰ introns.Then,circRNA circularization rates of RNA after in vitro transcription(IVT),primary circularization(IVC1),and secondary circularization(IVC2)were compared after purification.The constructed circRNA system was fur-ther applied to porcine reproductive and respiratory syndrome virus(PRRSV),and two circRNAs based on PRRSV GP5 protein were constructed and developed for in vitro expression.Results showed that circularization rates and protein expression effects of EGFP circRNA in IVC1 RNA and IVC2 RNA were similar,but both were significantly better than those of IVT RNA.Purity of EGFP circRNA reached 74％,and purities of two PRRSV GP5 protein circRNAs constructed using this preparation system were 71％and 64％,respectively.Western blot and indirect immunofluo-rescence assay(IFA)results indicated that both of the PRRSV GP5 protein circRNAs were suc-cessfully expressed.The results demonstrated that an easy-to-operate,low-cost circRNA prepara-tion system with high circularization rate was successfully constructed.Two PRRSV GP5 protein circRNA vaccines were successfully prepared using this system and expressed efficiently,which provides a reference for the development of animal circRNA vaccines and novel candidate vaccines against PRRSV.

Objective:To assess the current status of geriatrics department development in public general hospitals at or above the second grade in Shandong province.Methods:A cross-sectional survey was conducted from October 27 to November 3, 2023 using a web-based electronic questionnaire to investigate the current status of geriatrics department development in all public general hospitals at or above the second grade across 16 prefecture-level cities in Shandong province.The survey included participation from medical department staff and managers of geriatric medicine departments.Results:Shandong province has 355 public general hospitals at or above the second grade, of which 337 completed the questionnaire.Among these 337 hospitals, 92.28%(311/337)have established geriatric departments, 83.09%(280/337)have set up geriatric clinics, 69.14%(233/337)have independent geriatric wards, and 71.51%(241/337)have implemented comprehensive geriatric assessments(CGA).Regarding the configuration of geriatric departments, 60.24%(203/337)of hospitals met the requirement of having at least 20 ward beds, 34.42%(116/337)met the doctor-to-bed ratio requirement of at least 0.3, and 22.26%(75/337)met the nurse-to-bed ratio requirement of at least 0.6.Only 13 hospitals met all the requirements for geriatric wards, beds, doctors, and nurses, accounting for 3.86%(13/337)of the participating hospitals.Conclusions:The establishment of geriatrics departments in second-grade or higher public general hospitals in Shandong province has surpassed the national target in China ahead of schedule.Most hospitals have established geriatric clinics and wards and have implemented CGA.However, significant challenges remain, including a shortage of ward beds and a lack of medical staff.

Objective To analyze the reasons for the failure of subject screening in clinical trials of antineoplastic drugs and the impact of natriuretic criteria on the entry of subjects into clinical trials,to explore the strategies to improve the suc-cessful enrolment of screened subjects,and to provide reference bases for research institutes and sponsors in the formulation of na-triuretic criteria.Methods This study selected data from 40 drug clinical trials conducted at the Drug Clinical Trial Research Center of the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1,2016,to June 30,2022.It statistically described the collected data on the frequency and percentage composition of screening failures among participants and the inclu-sion and exclusion criteria in the protocols.Results A total of 425 subjects were screened out of 40 clinical trial programmers covering 8 tumor types,with the majority being＜65 years of age(333,78.4％),of which the most important reasons included vol-untary withdrawal(71,16.7％),tumor metastasis(52,12.2％),failure to recover from treatment of pre-existing disease(38,8.9％),failure of bone marrow function(19,4.5％),and non-compliant liver function(15,3.5％).Among the nadir indicators,the age of the subjects(100％),ECOG score(97.5％),bone marrow function(ANC:95.0％,PLT:97.5％,HB:97.5％),liver function(T-BiL:95.0％,ALT:87.5％,AST:95.0％),renal function(CR:80.0％),and viral screening(HIV:80.0％,HBV:70.0％,HCV:62.5％)were relatively stringent.Conclusion The main reasons for subject screening failure in clinical trials in oncology in our hospital are voluntary withdrawal,brain metastasis,and failure of their biochemical test standards,which are close-ly related to the setting of clinical trial nadir criteria.Therefore,an in-depth understanding of subjects'characteristics,accurate set-ting of appropriate nadir criteria,continuous improvement of trial design,and strengthening of communication with subjects to pro-vide more relevant information will help to improve the screening success rate of clinical trials.