[摘 要] 目的：利用单细胞RNA测序（scRNA-seq）解析结直肠癌（CRC）肿瘤微环境（TME）中B细胞的异质性特征，为基于B细胞的预后评估与免疫治疗提供理论依据。方法：采集原发CRC患者的新鲜手术切除样本（n = 36），进行scRNA-seq。采用Seurat（v5.0）进行细胞分群，Monocle3（v1.3）和scVelo（v0.3.0）分析细胞分化轨迹，GSEA识别功能通路，pySCENIC（v0.11.2）构建基因调控网络。结果：识别B细胞（24 652个）和浆细胞（49 138个）共11个功能亚型。拟时序分析显示B细胞从初始态向组织驻留态分化。应激适应性B细胞在肿瘤中富集（10.39%），其NOD样受体信号和抗原提呈通路显著激活。组织驻留性B细胞在肿瘤中占9.09%，其C型凝集素信号和内吞作用增强。迁移性B细胞在TNM Ⅱ期组织中比例最低（16.42%），氧化磷酸化等代谢通路显著富集。浆细胞呈终末分化状态，肿瘤中以IgG型为主（20.68%）。结论：应激适应性和组织驻留性B细胞可能促进肿瘤免疫逃逸，迁移性B细胞或具抗肿瘤潜力；同时，IgG型浆细胞可能与免疫抑制有关。

This paper focuses on the necessity and feasibility of the multidimensional integration of clinic, culture and language in the international education of acupuncture-moxibustion within a cross-cultural context. In view of the current gap between theory and practice, and the barrier of culture and language in the international education of acupuncture-moxibustion, it proposes the specific integration approaches, such as the "trinity teaching method" and "modularization of acupuncture courses", which develops the framework of international education of acupuncture-moxibustion, guided by "cultural exploration" in macroscopic view and implemented through "cultural experience", aiming to achieve a seamless integration of clinic, culture, and language. This initiative not only inherits and promotes Chinese acupuncture-moxibustion, maintains its unique position in global healthcare, but also fosters dialogue and exchange between Eastern and Western medicine. Ultimately, it enhances the international recognition of Chinese acupuncture-moxibustion. By offering fresh perspectives and methodologies, this paper paves the way for a more comprehensive and systematic approaches to international education of acupuncture-moxibustion, presenting the theoretical and practical significance in advancing the globalization of traditional Chinese medicine.
Humans ; Moxibustion ; Language ; Acupuncture/education* ; Acupuncture Therapy ; Culture ; China

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis. However, their involvement in optic neuropathy due to trauma and glaucoma remains unclear. Here, we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina. Deletion of IL-33 or ST2 exacerbated retinal ganglion cell (RGC) loss, retinal thinning, and nerve fiber degeneration following optic nerve (ON) injury. This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33^-/- mice. In vitro, rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors, thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants. Exogenous IL-33 treatment improved RGC survival in Il33^-/- and WT mice after ON injury, but not in ST2^-/- mice. Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.
Animals ; Interleukin-33/genetics* ; Interleukin-1 Receptor-Like 1 Protein/genetics* ; Optic Nerve Injuries/pathology* ; Retinal Ganglion Cells/pathology* ; Astrocytes/pathology* ; Mice ; Mice, Knockout ; Mice, Inbred C57BL ; Neuroprotection/physiology*

Objective·To establish a mouse model with dormant cancer and no obvious metastasis by combining the preimmune strategy with the mVenus-p27K-cell G0 phase indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system.Methods·The KPC1199 mouse pancreatic cancer cell line was transfected with the mVenus-p27K-cell G0 phase indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system to construct a stable expression cell line,KPC1199-PDL.After being cultured in the serum-free condition,KPC1199-PDL cells were sorted into mVenus(+)cells and mVenus(-)cells by flow cytometry,and the expression of G0 phase-related genes was verified by real-time fluorescence quantitative PCR(qPCR).Sensitivity of KPC1199-PDL cells to diphtheria toxin(DTX)and ganciclovir(GCV)was evaluated by CCK-8 assay.A transsplenic portal vein-hepatic metastasis model was constructed in wild-type C57BL/6 mice to validate the function of KPC1199-PDL cells in vivo by immunofluorescence technology.The KPC1199-PDL cells were injected subcutaneously into C57BL/6 mice,followed by in situ injection of DTX and GCV to ablate subcutaneous tumors 5 d later,to obtain preimmunized mice.The transsplenic portal vein-hepatic metastasis models were constructed in these mice.Bioluminescence imaging was used to evaluate subcutaneous tumor ablation and hepatic metastasis in the mice,and immunofluorescence assay was used to detect the distribution and dormant state of tumor cells in the livers of preimmunize mice.Results·The three tool systems were stably expressed in KPC1199-PDL cells,and their proliferative ability was not affected.In the serum starving condition,some KPC1199-PDL cells expressed the mVenus protein,indicating entry into the G0 phase;the mVenus(+)cells sorted out by flow cytometry exhibited significantly higher expression of G0 phase-related genes(all P<0.05)and significantly lower expression of the proliferation-related gene compared with mVenus(-)cells(P<0.05).The CCK-8 assay demonstrated high sensitivity of KPC1199-PDL cells to DTX and GCV.In vivo experiments confirmed that KPC1199-PDL cells could be effectively traced through tdTomato protein expression,and could indicate entry into the G0 phase through mVenus protein expression.Following subcutaneous tumor implantation and drug ablation,preimmunized mice were successfully obtained.In the subsequent transsplenic portal vein-hepatic metastasis model,no metastatic signals were observed in the liver by bioluminescence imaging,but single or small clusters of G0 phase tumor cells expressing both mVenus and tdTomato,not expressing the proliferation marker Ki67,were detected in liver tissue sections by immunofluorescence analysis.Conclusions·A recognizable and traceable dormant cancer model is constructed with the combination of the preimmune mouse model of pancreatic cancer,the mVeneus-p27K-indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system.

Objective To observe the value of intravascular ultrasound(IVUS)for assisting endovascular therapy for renal artery stenosis(RAS).Methods Thirty patients with RAS who underwent endovascular therapy were retrospectively analyzed.Parameters of renal artery and plaques in RAS segment measured with CT angiography(CTA)and IVUS before treatment were compared.Bland-Altman diagram was performed to evaluate the consistency of lumen cross-sectional stenosis rate and plaque eccentricity index between CTA and IVUS.The stent parameters measured with IVUS were recorded immediately after implantation of balloon-expandable covered stents.Results Before treatment,the minimum lumen diameter,lumen cross-sectional stenosis rate and stenotic segment length of IVUS were all larger,while maximum lumen diameter and lumen eccentricity index of IVUS were both smaller than those of CTA(all P＜0.05).No significant difference of plaque eccentricity index,plaque type nor stenosis distal remodeling was found between CTA and IVUS(all P＞0.05).The average difference between IVUS and CTA for evaluating lumen cross-sectional stenosis rate and plaque eccentricity index was-0.020(-0.096,0.050)and-0.020(-0.130,0.091),respectively.The consistency of IVUS and CTA for evaluating plaque eccentricity index was better than that of lumen cross-sectional stenosis rate.The stent symmetry,stent eccentricity index,stent expansion coefficient and stenosis coverage rate immediately after implantation measured with IVUS was(82.69±14.61)%,(1.54±9.16)%,(99.81±10.70)%and 100%,respectively.Among 30 cases,2 cases(2/30,6.67%)underwent postdilation since poor stent apposition.Conclusion IVUS could assist evaluating lumen and plaque parameters of stenotic renal arteries,guiding stent release and real-timely monitoring the effect of endovascular therapy.

Objective:To comprehensively search the relevant literature on prone position-cardiopulmonary resuscitation (PP-CPR) in adults at home and abroad, analyze the content, summarize the evidence, and provide reference for clinical health care professionals.Methods:Systematic search of CNKI, China Biomedical Literature Service System (SinoMed), Wanfang Data, VIP database, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochran Library, Web of Science, Scopus literature database and other Chinese and English databases was conducted. The search period was from inception to June 15 in 2024. The contents of PP-CPR from randomized controlled trial (RCT), non-RCT (prospective or retrospective), cohort studies and case reports were extracted and systematically analyzed. The search results were standardized by the method of scoping review.Results:A total of 523 articles were obtained through preliminary search, and 14 references and gray literature were retrieved, totaling 537 articles. After strict screening by two researchers, a total of 26 literatures were included, 3 were non-RCT and 23 were case reports, involving 12 countries, including 3 in Chinese, 19 in English, 2 in French, 1 in German, and 1 in Korean. Three non-RCT demonstrated that compared with standard cardiopulmonary resuscitation (CPR), PP-CPR could produce higher pressure, and provide good respiratory and circulatory support. A total of 25 adult patients were included in the 23 case reports, of which 17 reported total recovery time and 13 reported PP-CPR time ≤ 5 minutes, all of which recovered spontaneous circulation, indicating the effectiveness of PP-CPR technology. In terms of final outcome, 4 patients (16.0%) died and 21 patients (84.0%) survived, indicating that PP-CPR technology could provide timely blood circulation and improve clinical outcomes for prone cardiac arrest patients. Among the 11 patients who reported complications after resuscitation, no neurological damage was found in the short-term outcomes, indicating that PP-CPR technology had a certain level of safety.Conclusions:PP-CPR can provide timely blood circulation for patients with cardiac arrest who are unable to lie supine quickly, and win "golden time" for defibrillation and further treatment. In clinical practice, medical staff need to evaluate the emergency environment, the number of rescuers and the specific condition of the patient, and implement first aid as soon as possible, so as to reduce the time of no blood flow in the vital organs of patients with cardiac arrest in prone position, and improve the clinical prognosis.

Objective To investigate the clinical characteristics of patients with pancreatic cancer (PC) complicated with new-onset diabetes mellitus (DM), and to provide a basis for defining a high-risk group for PC. Methods The 426 PC cases admitted to the First Hospital of Shanxi Medical University from January 2016 to December 2021 were retrospectively selected and divided into new DM group (disease duration ≤2 years, n =74), long-term DM group (disease duration > 2 years, n =50) and simple PC group (no DM, n =302). We collected their basic demographic information, smoking and drinking history, disease history, family history, DM medication, clinical characteristics (first symptoms, tumor diameter, mass location, pancreatic duct dilatation, surgical resection) and biochemical indexes (FPG, CA19-9, CA125). The glycemic status of those who underwent surgical resection was monitored for six months after surgery. The t -test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test and the Fisher's exact test were used for comparison of categorical data between two groups. Results Of the 426 PC patients, 68.3% were male and 31.7% were female. New-onset DM accounted for 59.7% of the PC patients with DM. Compared with the long-term DM group, the new-onset DM group had a lower age of onset ( t =-2.041, P =0.043), a lower proportion of combined hypertension ( χ 2 =3.950, P =0.047), a lower family history of DM ( χ 2 =3.893, P =0.048), a lower FPG level ( Z =-2.740, P =0.005), a higher proportion of smokers ( χ 2 =7.032, P =0.008), significant weight change ( Z =-2.161, P =0.031), larger tumor diameter ( Z =-2.269 P =0.023), high proportion of those with pancreatic duct dilatation ( χ 2 =4.870, P =0.027), and significant differences in DM medication ( χ 2 =1.976, P < 0.05). At six months of follow-up, 7 patients (36.8%) in the new-onset DM surgery group had glycemic improvement, but none in the long-term DM surgery group. Compared with the PC-only group, the new-onset DM group had a lower age of onset ( t =-0.273, P =0.039), a slightly higher BMI level ( t =-2.139, P =0.033), a significant weight change ( Z =-2.262, P =0.024), a higher proportion of complicated hypertension ( χ 2 =17.438, P < 0.001), a higher FPG level ( Z =-8.322, P < 0.001), and a high proportion of dilated pancreatic ducts ( χ 2 =3.983, P =0.046). Conclusion Among PC patients, the onset age is relatively young in those complicated with new-onset DM. Patients with new-onset DM who smoke, have no family history of DM, have significant weight loss, have difficulty in controlling FPG levels, and pancreatic duct dilatation may be at high-risk for PC and should be screened early.

Objective:To determine the risk factors of extubation failure and its effect on the prognosis of patients who had successfully passed a spontaneous breathing trial (SBT).Methods:The clinical data of patients with mechanical ventilation more than 24 hours who passed SBT admitted to department of intensive care unit (ICU) of First Hospital of Qinhuangdao from November 2018 to November 2019 were retrospectively analyzed. According to the outcome of weaning within 48 hours after weaning, patients were divided into weaning success group and weaning failure group. The baseline data, the presence of basic cardiopulmonary diseases, B-type natriuretic peptide (BNP), fluid balance, albumin and hemoglobin within 24 hours before weaning, the time of mechanical ventilation before weaning, rapid shallow breathing index (RSBI) during SBT, oxygenation index, cough peak flow at the end of SBT, and prognostic indicators were collected. The outcome of weaning was taken as the dependent variable, and the observation factors were taken as the independent variable for univariate analysis. The factors with statistical significance in univariate analysis were analyzed by binary Logistic regression to determine the influencing factors of weaning failure.Results:Of the 204 patients, 167 (81.9%) were successfully weaned, and 37 (18.1%) failed. Compared with the weaning success group, the total duration of mechanical ventilation and the length of ICU stay in the weaning failure group were significantly longer [days: 13.0 (7.5, 23.5) vs. 5.0 (3.0, 8.0), 17.0 (12.5, 31.0) vs. 10.0 (6.0, 15.0), both P < 0.01], and the tracheotomy rate and mortality were significantly higher (32.4% vs. 0%, 51.4% vs. 0%, both P < 0.01). Univariate analysis showed that there were significant differences in age, proportion of patients with cardiopulmonary diseases, BNP and cough peak flow between weaning failure group and weaning success group [age (years old): 70.65±15.78 vs. 62.69±15.82, cardiopulmonary diseases: 62.2% vs. 24.6%, BNP (ng/L): 416.87 (32.70, 1 225.80) vs. 45.36 (10.00, 273.60), cough peak flow (L/min): 59.89±9.06 vs. 83.84±16.52, all P < 0.01]. However, there were no significant differences in gender, acute physiology and chronic health evaluationⅡ (APACHEⅡ) at admission, mechanical ventilation time before weaning, albumin, hemoglobin, oxygenation index, RSBI and fluid balance 24 hours before weaning between weaning failure group and weaning success group [male: 51.4% vs. 68.3%, APACHEⅡ: 16.70±6.65 vs. 15.67±6.28, mechanical ventilation time before weaning (days): 6.0 (2.5, 11.0) vs. 5.0 (3.0, 8.0), albumin (g/L): 27.78±4.15 vs. 27.76±4.46, hemoglobin (g/L): 102.43±15.80 vs. 100.61±17.19, oxygenation index (mmHg, 1 mmHg = 0.133 kPa): 359.33±79.83 vs. 365.75±78.23, RSBI (times·L -1·min -1): 50.73±24.97 vs. 46.76±15.53, positive fluid balance: 70.3% vs. 69.5%, all P > 0.05]. The results of binary Logistic regression analysis showed that age ≥ 75 years old [odds ratio ( OR) = 3.099, 95% confidence interval (95% CI) was 1.003-9.574, P = 0.049], presence of cardiopulmonary diseases ( OR = 3.599, 95% CI was 1.126-11.498, P = 0.031), BNP within 24 hours before weaning ( OR = 1.002, 95% CI was 1.000-1.003, P = 0.005) were the risk factors of extubation failure, while cough peak flow at the end of SBT was the protective factor ( OR = 0.869, 95% CI was 0.823-0.917, P = 0.000). Conclusions:For patients who had successfully passed SBT, age ≥ 75 years old, the presence of cardiopulmonary diseases and an increased level of BNP within 24 hours were the risk factors of extubation failure. In addition, the higher the cough peak flow at the end of SBT, the lower the risk of weaning failure will be.