Objective To construct a nomogram prediction model for major adverse cardiovascular events(MACE)within 1 year after percutaneous coronary intervention(PCI)in elderly patients with acute coronary syndrome(ACS).Methods A retrospective analysis was conducted on 551 patients with diagnosed ACS and undergoing PCI in Department of Cardiovascular Medicine of Air Force Medical Center from 1 January 2020 to 1 April 2022.According to the occurrence of MACE during 1 year of follow-up,they were classified into MACE group(n=176)and non-MACE group(n=375).Risk factors for the occurrence of MACE in elderly ACS patients within 1 year after PCI were analysed using univariate and multivariate logistic regression,a nomogram prediction model was constructed,and the predictive power of the model was assessed using the area under the ROC curve(AUC).Results The MACE group had significantly higher Gensini score,systemic immune-inflammation index,and GRACE score,but obviously lower prognostic nutritional index than the non-MACE group(P＜0.01).Multivariate logistic regression analysis showed that recent smoking(OR=2.222,95％CI:1.361-3.628,P=0.010),hyperlipidaemia(OR=1.881,95％CI:1.145-3.089,P=0.013),prognostic nutritional index(OR=4.645,95％CI:2.788-7.739,P=0.001),LVEF(OR=5.177,95％CI:3.160-8.483,P=0.001),systemic immune-inflammation index(OR=5.396,95％CI:3.179-9.159,P=0.001),and preoperative di-agnosis of non-STEMI(OR=2.829,95％CI:1.356-5.901,P=0.006)or STEMI(OR=3.451,95％CI:1.596-7.463,P=0.002)were independent influencing factors for occurrence of MACE after PCI in elderly ACS patients.ROC curve analysis showed that the AUC value of the nomo-gram model for predicting MACE within 1 year after PCI in elderly ACS patients was 0.888.Con-clusion Our developed nomogram model is simple and practical,and can effectively predict the occurrence of MACE within 1 year after PCI in elderly ACS patients.And external validation should be carried out to ensure its generality.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:Using single cell sequencing to analyze the characteristics of the immune repertoire of SARS-CoV-2 pa-tients at different infection stages,and to explore the possible pathogenesis.Methods:Obtaining data in the NCBI database,and healthy control,progression and convalescence groups were set up.Analysis of single cell sequencing data by RStudio,Origin,Hipliot and Excel software.Results:TCR plays an important role in antigen recognition and virus clearance.Characteristics of the three immune repertoires are very different.The number of clones exceeded 26.92%.The length distribution of α chain CDR3 was con-centrated on 14 amino acids,while β-chain was concentrated on 15 amino acids.The frequency of gene fragments in V and J regions were different,and the frequency of TRAV13-1,TRAJ20,TRBV20-1 and TRBJ2-1 were statistically significant(P<0.05).Further V-J gene combination analysis showed that there were significant differences in the frequency of single chain V-J between the control group and the progression group,the control group and the rehabilitation group(P<0.05).The highest frequency of αβ double chain V-J in the control group was TRAV19-J34-TRBV4-1-J2-1,the highest frequency of αβ double-stranded V-J in the progression group was TRAV12-1-J30-TRBV19-1-J2-1,and the highest frequency of αβ double chain V-J in the convalescence group was TRAV12-2-J52-TRBV7-9-J1-5.Conclusion:This study analyzes the global characteristics of T cells in the immune repertoire,which is helpful to understand the pathogenesis of SARS-CoV-2 patients,timely and effective treatment of patients in the early stages of infection.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Background: Arctic-like (AL) lineages of rabies viruses (RABVs) remains endemic in some Arctic and Asia countries. However, their evolutionary dynamics are largely unappreciated. Objectives: We attempted to estimate the evolutionary history, geographic origin and spread of the Arctic-related RABVs. Methods: Full length or partial sequences of the N and G genes were used to infer the evolutionary aspects of AL RABVs by Bayesian evolutionary analysis. Results: The most recent common ancestor (tMRCA) of the current Arctic and AL RABVs emerged in the 1830s and evolved independently after diversification. Population demographic analysis indicated that the viruses experienced gradual growth followed by a sudden decrease in its population size from the mid-1980s to approximately 2000.Genetic flow patterns among the regions reveal a high geographic correlation in AL RABVs transmission. Discrete phylogeography suggests that the geographic origin of the AL RABVs was in east Russia in approximately the 1830s. The ancestral AL RABV then diversified and immigrated to the countries in Northeast Asia, while the viruses in South Asia were dispersed to the neighboring regions from India. The N and G genes of RABVs in both clades sustained high levels of purifying selection, and the positive selection sites were mainly found on the C-terminus of the G gene. Conclusions The current AL RABVs circulating in South and North Asia evolved and dispersed independently.

Objective:To analyze the prognosis of patients with positive resection margin after radical prostatectomy, as well as the prostate-specific antigen (PSA)level and risk factors for PSA progression.Methods:A retrospective analysis was performed on the data of 141 patients with pathologically diagnosed prostate cancer who underwent RP from May 2012 to August 2020 in Beijing Hospital. The mean age was (67.4±6.7)years, the preoperative median PSA was 9.6 (1.4-152.8) ng/ ml and the median follow-up time was 56 months. Postoperative pathology was T 2 stage 74 (52.5%), T 3 stage 63 (44.7%), T 4 stage 4 (2.8%). Biochemical recurrence after radical resection was defined as PSA rose to more than 0.2 ng/ml and showed an upward trend after two consecutive follow-ups. In this study, serum PSA ≥ 0.1 ng/ml without biochemical recurrence after radical operation was defined as PSA progression. The PSA level, risk factors of PSA progression and prognosis of patients with positive resection margin were analyzed. Univariate and multivariate Cox regression analysis was used to analyze the correlation between age, preoperative PSA level, pathological stage (pT), ISUP classification, surgical approach, lymph node dissection, single/multiple positive margins and PSA progression. Results:The median follow-up of 141 patients was 52 months(1-104 months). There were 69 (48.9%) patients in the PSA progression group and 72 (51.1%) patients in the non PSA progression group. In the PSA progression group, 13 (18.8%) patients did not receive treatment and 8 (61.5%) patients had biochemical recurrence. 4 (5.8%) patients received radiotherapy alone, and 2 (50.0%) patients had biochemical recurrence. 52 (75.4%) patients received endocrine therapy or endocrine therapy combined with radiotherapy, and 5 (9.6%) patients developed castration resistance. Multivariate Cox regression analysis showed preoperative PSA ( HR=1.015, 95% CI 1.005-1.025, P =0.004), ISUP grade and group ( HR=1.351, 95% CI 1.091-1.673, P =0.006), surgical method ( HR=2.233, 95% CI 1.141-4.370, P =0.019) was correlated with PSA progression. Conclusions:The incidence of surgical positive margin is high after RP. Nearly half of the patients with surgical positive margin developed a PSA progression status. Preoperative PSA, ISUP grade group, and the surgical approach are risk factors for PSA progression in patients with positive surgical margins. Patients with these risk factors should be monitored more closely and treated more aggressively.