Objective To explore macrophage subpopulations in ischemic stroke (IS) by using single-cell RNA sequencing (scRNA-seq) data analysis and High-Dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Methods Based on single-cell sequencing data, transcriptomic information for different cell types was obtained, and macrophages were selected for subpopulation identification. hdWGCNA, cell-cell communication, and pseudotime trajectory analysis were used to explore the characteristics of macrophage subpopulations following IS. Key genes related to IS were identified using microarray data and validated for diagnostic potential through Receiver Operating Characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential functions of these genes. Results The scRNA-seq data analysis revealed significant changes in macrophage subpopulation composition after IS. A specific macrophage subpopulation enriched in the stroke group was identified and designated as MCAO-specific macrophages (MSM). Pseudotime trajectory analysis indicated that MSM cells were in an intermediate stage of macrophage differentiation. Cell-cell communication analysis uncovered complex interactions between MSM cells and other cells, with the CCL6-CCR1 signaling axis potentially playing a crucial role in neuroinflammation. Two gene modules associated with MSM were identified via hdWGCNA, significantly enriched in pathways related to NOD-like receptors and antigen processing. By integrating differentially expressed MSM genes with conventional transcriptomic data, three IS-related hub genes were identified: Arg1, CLEC4D, and CLEC4E. Conclusion This study reveals the characteristics and functions of macrophage subpopulations following IS and identifies three hub genes with potential diagnostic value, providing novel insights into the pathological mechanisms of IS.
Macrophages/metabolism* ; Computational Biology/methods* ; Single-Cell Analysis/methods* ; Transcriptome ; Ischemic Stroke/metabolism* ; Animals ; Gene Regulatory Networks ; Gene Expression Profiling ; Humans ; Male

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans ; Surgical Wound Infection/epidemiology* ; Male ; Female ; Risk Factors ; Retrospective Studies ; Middle Aged ; Adult ; Case-Control Studies ; Fractures, Bone/surgery* ; Aged ; Drug Resistance, Bacterial ; Logistic Models ; Anti-Bacterial Agents/therapeutic use* ; Incidence ; Bacteria/drug effects*

OBJECTIVE: To initially investigate the function of neuronal pentraxin 1 (NPTX1) gene on osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). METHODS: hBMSCs were induced to undergo osteogenic differentiation, and then RNA was collected at different time points, namely 0, 3, 7, 10 and 14 d. The mRNA expression levels of key genes related with osteogenic differentiation, including runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and NPTX1, were detected on the basis of quantitative real-time polymerase chain reaction (qPCR) technology. In order to establish a stable NPTX1-knockdown hBMSCs cell line, NPTX1 shRNA lentivirus was constructed and used to infect hBMSCs. ALP staining, alizarin red (AR) staining, and qPCR were employed to assess the impact of NPTX1-knockdown on the osteogenic differentiation ability of hBMSCs. RESULTS: The results showed that during the osteogenic differentiation of hBMSCs in vitro, the mRNA expression levels of osteogenic genes RUNX2, ALP and OCN significantly increased compared with 0 d, while NPTX1 expression decreased markedly (P < 0.01) as the osteogenic induction period exten-ded. At 72 h post-infection with lentivirus, the result of qPCR indicated that the knockdown efficiency of NPTX1 was over 60%. After knocking down NPTX1 in hBMSCs, RNA was extracted from both the NPTX1-knockdown group (sh NPTX1 group) and the control group (shNC group) cultured in regular proliferation medium. The results of qPCR showed that the expression levels of osteogenic-related genes RUNX2 and osterix (OSX) were significantly higher in the sh NPTX1 group compared with the shNC group (P < 0.01). ALP staining revealed a significantly deeper coloration in the sh NPTX1 group than in the shNC group at the end of 7 d of osteogenic induction. AR staining demonstrated a marked increase in mineralized nodules in the sh NPTX1 group compared with the shNC group at the end of 14 d of osteogenic induction. CONCLUSION NPTX1 exerts a modulatory role in the osteogenic differentiation of hBMSCs, and its knockdown has been found to enhance the osteogenic differentiation of hBMSCs. This finding implies that NPTX1 could potentially serve as a therapeutic target for the treatment of osteogenic abnormalities, including osteoporosis.
Humans ; Mesenchymal Stem Cells/cytology* ; Osteogenesis/genetics* ; Cell Differentiation/genetics* ; Nerve Tissue Proteins/genetics* ; Cells, Cultured ; C-Reactive Protein/genetics* ; RNA, Small Interfering/genetics* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Bone Marrow Cells/cytology* ; Gene Knockdown Techniques ; Osteocalcin/metabolism* ; Alkaline Phosphatase/metabolism* ; RNA, Messenger/metabolism*

Objective Based on a complete Freund's adjuvant(CFA)-induced chronic inflammatory pain model,we compared and analyzed the differences in anti-inflammatory and analgesic effects of moxibustion intervention initiated at different timepoints,aiming to identify the optimal timing for moxibustion intervention.The goal is to establish standardized intervention protocols for basic research on the anti-inflammatory and analgesic effects of moxibustion.Methods Male C57BL/6 mice were randomly divided into 3 groups based on the moxibustion initiation timepoints of 4,7,and 10 d after modeling.Then,the mice in each group were randomly assigned to 3 subgroups,including a control group,a model group,and a moxibustion group,with 8 mice in each subgroup.Chronic inflammatory pain was induced by injecting 20 μL of CFA into the sole of the right hind paw.Moxibustion applied at the"Zusanli"acupoint for 30 minutes started on the 4th,7th,and 10th days after modeling,and the intervention continued for 7 days.The latency of paw withdrawal to thermal radiation was measured to evaluate the pain threshold before modeling,after modeling,and on the 1st,4th,and 7th days of treatment.Foot volume was measured to assess toe swelling before modeling,after modeling,and on the 1st and 7th days of treatment.Results Compared with the control group,the model group exhibited a reduced pain threshold(P＜0.0001)and increased paw volume(P＜0.0001).Compared with the model group,the subgroups receiving moxibustion intervention initiated on the 4th,7th,and 10th days post-modeling exhibited an increased pain threshold(P＜0.05,P＜0.0001).However,the paw volume of the subgroups receiving moxibustion intervention initiated on the 4th day post-modeling increased(P＜0.0001),while those of the subgroups receiving moxibustion intervention initiated on the 7th and 10th days post-modeling decreased(P＜0.0001).Among the intervention subgroups receiving moxibustion initiated on days 4,7,and 10,the day 7 intervention-initiating subgroup showed significant increase in pain threshold(P＜0.05,P＜0.0001),and the day 7 and day 10 intervention-initiating subgroups showed significantly reduced paw volume(P＜0.0001).Conclusion Considering both the analgesic and anti-inflammatory effects of moxibustion,day 7 post-modeling may be the optimal time for moxibustion to achieve effective anti-inflammatory and analgesic outcomes.

Clinically,patients with high-risk cholecystitis are often facing the therapeutic choice of permanent cholecystostomy drainage or high-risk surgery.With the development of percutaneous interventional therapy techniques in recent years,minimally invasive treatment have provided more therapeutic options for these patients.Cryoablation,chemical ablation,and gallbladder-intestine anastomosis are considered as the promising methods for the treatment of cholecystitis.Different combinations of percutaneous cholecystostomy(PC)with sequential cryoablation,chemical ablation,or gallbladder-intestine internal drainage have achieved a high success rate in treating cholecystitis,thus,providing patients with an option of non-surgical resection.This article aims to make a comprehensive review about various percutaneous treatment methods for cholecystitis so as to provide useful references for clinical practice.

Most of the medical colleges and universities in China follow the traditional three-stage teaching mode centering on subjects, and a number of colleges and universities have implemented the teaching mode of organ-system-based curriculum (OSBC). With the OSBC course for the nervous system in our university as an example, this article analyzes the advantages and challenges of OSBC course of the nervous system in the context of integrative medicine.
Neurology

Objective:To explore the clinicopathological and genetic characteristics of sporadic medullary thyroid carcinoma (MTC) and new therapeutic targets for sporadic MTC.Methods:Based on family and personal disease history, we identified 32 sporadic MTC who underwent surgical resection from Jan 2010 to Dec 2022. Clinicopathological and immunohistochemical features were analyzed in all patients, while 6 of them were subject to the whole exome sequencing (WES).Results:Compared with those of low-grade sporadic MTC, patients with high-grade tumors were more likely to have lymph node metastasis at presentation ( χ2=4.428, P=0.040); less likely to be cured by biochemical treatment ( χ2=4.072, P=0.044). Pathological grading scheme, biochemical cure, and TNM stage were independent risk factors of disease free survival. WES was performed on 6 pairs of normal tissues. We screened RET and RAS as driver mutations, and the mutation ratio was 3/6 respectively. Patients with RET or RAS mutations had no recurrence. In addition, we detected PDGFRA somatic mutation, with a mutation ratio of 1/6. Conclusions:For sporadic MTC cases, the pathological grading system has important prognostic value, and RET and RAS somatic mutations are the main driver mutations. PDGFRA are potential therapeutic targets for sporadic MTC.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

Objectives:To analyze and compare the disease burden of ischemic stroke due to tobacco exposure (including active and passive smoking) and its changing trends in China from 1990 to 2019,and to provide a reference for precise prevention and control of ischemic stroke. Methods:Based on the Global Burden of Disease Study 2019 database,we analyzed the burden of ischemic stroke disease attributable to tobacco exposure and its trends in different age and sex populations in China from 1990 to 2019,and compared the epidemiological differences in the burden of ischemic stroke disease attributable to active versus passive smoking. Results:Between 1990 and 2019,the disease burden of ischemic stroke attributable to tobacco exposure showed a decreasing trend in China and globally,but the decrease was relatively small in China.In 2019,the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) of ischemic stroke attributable to tobacco exposure in China were 10.64/100000 and 239.39/100000,both higher than the global average levels (5.85/100000 and 140.23/100000 respectively).The actual mortality and disability-adjusted life year (DALY) rates for ischemic stroke due to tobacco exposure in 2019 increased by 103.79％ and 90.48％,respectively,compared with 1990.There was a sex difference in the disease burden of ischemic stroke due to active and passive smoking,with the number of deaths,mortality,DALY,and DALY rates for ischemic stroke due to active smoking being significantly higher in men than in women.Conversely,the burden of ischemic stroke due to passive smoking was higher in women.At the age level,ischemic stroke attributable to both active and passive smoking presented the highest number of deaths,mortality,and DALY rates among those ≥70 years of age.Whereas DALY for ischemic stroke attributable to active smoking was mainly concentrated in those aged 50-69 years,DALY for ischemic stroke attributable to passive smoking was mainly concentrated in those aged ≥70 years. Conclusions:The disease burden of ischemic stroke attributable to tobacco exposure is higher in China than the global average level.The burden of ischemic stroke disease attributable to active and passive smoking varies significantly by sex and age,and more targeted tobacco control policies should be developed in China.

Objective:To analyze the current prevalence of pre-diabetes (PDM) and its relationship with overweight and obesity in an adult health check-up population.Methods:This study was a cross-sectional and retrospective cohort study and was applied using whole-cluster random sampling method. A total of 491 379 adults who underwent health check-ups at the Health Management Centre of Sichuan Provincial People′s Hospital from January 2017 to July 2023 were selected to analyze the epidemiological characteristics of PDM and overweight-obesity, as well as the trend of change over time. A retrospective cohort study was conducted on 19 001 of the subjects who underwent≥3 health check-ups and did not have diabetes and PDM at baseline, and the relationships between body mass index, waist circumference and the risk for developing PDM were analyzed using Cox proportional risk regression models. And the dose-response relationship between body mass index, waist circumference and the risk for developing PDM was analyzed using restricted cubic spline regression (RCS).Results:Of the 491 379 cases included in the cross-sectional study, 275 084 were male and 216 295 were female, 163 158 cases were under 40 years old, and 328 221 cases were 40 years old and above; the total prevalence of PDM was 19.41% in 2017-2023, with an overall increasing trend. Of the 19 001 people included in the cohort study, a total of 2 487 (13.09%) new cases of PDM were identified at the end of follow-up. After adjusting for confounding factors, overweight ( HR=1.150, 95% CI: 1.047-1.263), obesity ( HR=1.335, 95% CI: 1.149-1.552) and abdominal obesity ( HR=1.218, 95% CI: 1.105-1.342) were risk factors for PDM. The risk of PDM rised with the increase of body mass index (>22.9 kg/m 2, Pnon-linear=0.973) and waist circumference (>80 cm, Pnon-linear=0.830), with a linear dose-response mode. In different gender and age groups, it was found the greater the body mass index (>24.1 kg/m 2 for men,>21.5 kg/m 2 for women;>23.3 kg/m 2 for age≥40 years,>24.1 kg/m 2 for age<40 years) and waist circumference (>85 cm for men, >73 cm for women; >82 cm for age ≥40 years, >85 cm for age <40 years), the higher the risk of PDM. Conclusions:The prevalence of PDM is on the rise in the adult health check-up population. To prevent PDM, it is necessary to control the body mass index and waist circumference to a lower level than the overweight and obesity standards.