Objective:To investigate the serum lactate level in patients with rheumatoid arthritis(RA)and its relationship with disease activity,and to analyze the effect of sodium lactate on the activation of CD4+T cells,the ability of secreting cytokines and CD4+T cell subsets in peripheral blood of the RA patients.Methods:The peripheral blood of healthy controls(HC)and RA patients was collected,and the content of lactate in the supernatant was detected by lactate detection kit,the correlation between the content of lactate and the disease score of the RA patients was analyzed;the activation level of CD4+T cells,the proportion of CD4+T cell subsets and the cytokines secreted by CD4+T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate.Results:The serum lactate level in the RA patients(n=66)was significantly higher than that in the HC(n=60,P＜0.001),and there was a certain correlation with disease activity score in 28 joints(DAS28)-C-reactive protein(CRP)(r=0.273,P=0.029),The levels of rheumatoid factor[RF,197.50(26.03,783.00)IU/mL vs.29.30(0.00,102.60)IU/mL,P＜0.01],CRP[37.40(11.30,72.60)mg/L vs.5.83(2.36,12.45)mg/L,P＜0.001],were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L,however,there was no significant difference in the expres-sion of erythrocyte sedimentation rate[ESR,42.00(19.00,77.00)mm/h vs.25.00(12.50,45.50)mm/h,P＞0.05]and anti-cyclic citrullinated peptied(CCP)antibody[82.35(17.70,137.00)RU/mL vs.68.60(25.95,119.70)RU/mL,P＞0.05].Compared with the control group,the expression of PD-1(46.15％±8.54％vs.41.67％±9.98％,P＜0.001),inducible costimulatory molecule(ICOS,5.77％±8.60％vs.18.65％±7.94％,P＜0.01)and CD25(25.89％±5.80％vs.22.25％±4.59％,P＜0.01)on the surface of CD4+T cells in the RA patients treated with sodium lactate was significantly increased.Compared with the control group,the proportion of Th17(4.62％±1.74％vs.2.93％±1.92％,P＜0.05)and Tph(28.02％±6.28％vs.20.32％±5.82％,P＜0.01)cells in CD4+T cells of the RA patients in the sodium lactate treatment group increased.Compared with the con-trol group,the expression of IL-21(5.73％±1.59％vs.4.75％±1.71％,P＜0.05)inCD4+Tcells was up-regulated in the RA patients treated with sodium lactate.Conclusion:The level of serum lactate in RA patients is increased,which promotes the activation of CD4+T cells and the secretion of IL-21,and up-regulates the proportion of Th 17 and Tph cells in the RA patients.

Objective To analyze the risk factors of cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy. Methods 530 patients with esophageal cancer underwent thoracoscopic?lapacoscopic esophagectomy at the Cancer Hospital, Chinese Academy of Medical Sciences from Jan 2011 to Dec 2015. The demographic, surgical and clinical data of patients were retrospectively analyzed. Multivariate logistic regression was used to evaluate risk factors of cervical anastomotic leakage in these patients. Results A total of 530 patients undergoing thoracoscopic?lapacoscopic esophagectomy were enrolled in this study. There were 421 males and 109 females. The mean age was (59.40±8.08) years old, and 91 patients with cervical anastomotic leakage. Sigle factor analysis revealed that the risk grading by American Society of Aneshesiologists, previous history of chest surgery, respiratory comorbidity, diffusion capacity for carbon monoxide of the lung, operation time, anastomosis, average days of postoperative hospitalization, death within 30 days after surgery, respiratory complications, pleural effusion or empyema, and poor healing of the incision were statistically associated with cervical anastomotic leakage (all P＜0.05). Multivariate analysis showed that previous history of chest surgery, hepatic insufficiency, manual anastomosis, prolonged postoperative hospitalization, and poor healing of the incision were independent risk factors for cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy ( all P＜0.05 ). Conclusions Previous history of chest surgery, hepatic insufficiency, poor healing of the incision, manual anastomosis and prolonged postoperative hospitalization were significantly associated with cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy. It′s important to strengthen perioperative nursing and surgical techniques to prevent anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy.

Objective To analyze the risk factors of cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy. Methods 530 patients with esophageal cancer underwent thoracoscopic?lapacoscopic esophagectomy at the Cancer Hospital, Chinese Academy of Medical Sciences from Jan 2011 to Dec 2015. The demographic, surgical and clinical data of patients were retrospectively analyzed. Multivariate logistic regression was used to evaluate risk factors of cervical anastomotic leakage in these patients. Results A total of 530 patients undergoing thoracoscopic?lapacoscopic esophagectomy were enrolled in this study. There were 421 males and 109 females. The mean age was (59.40±8.08) years old, and 91 patients with cervical anastomotic leakage. Sigle factor analysis revealed that the risk grading by American Society of Aneshesiologists, previous history of chest surgery, respiratory comorbidity, diffusion capacity for carbon monoxide of the lung, operation time, anastomosis, average days of postoperative hospitalization, death within 30 days after surgery, respiratory complications, pleural effusion or empyema, and poor healing of the incision were statistically associated with cervical anastomotic leakage (all P＜0.05). Multivariate analysis showed that previous history of chest surgery, hepatic insufficiency, manual anastomosis, prolonged postoperative hospitalization, and poor healing of the incision were independent risk factors for cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy ( all P＜0.05 ). Conclusions Previous history of chest surgery, hepatic insufficiency, poor healing of the incision, manual anastomosis and prolonged postoperative hospitalization were significantly associated with cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy. It′s important to strengthen perioperative nursing and surgical techniques to prevent anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy.

Objective:To investigate frequency and function of peripheral CD4+CD28-T cells in immune thrombocytopenia(ITP)patients,to deeply understand pathogenesis of ITP.Methods:A total of 30 ITP patients treated in The Second Affiliated Hospi-tal of Dalian Medical University from January 2021 to June 2022 were recruited,and 30 gender/age-matched healthy volunteers were served as control group.Peripheral anticoagulation was collected and mononuclear cells(PBMC)were extracted,frequencies and func-tions of CD4+CD28-T cells in PBMC was analyzed by flow cytometry,plasma levels of IL-18 and IL-18BP in ITP patients were detected by ELISA,and frequencies of CD4+CD28-T cells before and after treated with IL-18 were determined by flow cytometry.Results:Frequencies of CD4+CD28-T cells in peripheral blood of ITP patients were significantly higher than that of healthy control group,and CD4+CD28-T cells had a stronger ability to secrete IFN-γ and TNF-α;level of IL-18 was higher in plasma from ITP patients;IL-18 could increase frequency of CD4+CD28-T cells in PBMC of ITP patients.Conclusion:Frequency of CD4+CD28-T cells in peripheral blood of ITP patients is significantly increased,and has stronger ability to secrete inflammatory factors.

OBJECTIVE: Immunotherapy has brought significant clinical benefits to a subset of patients, but has thus far been disappointing in the treatment of immunologically "cold" tumors. Existing biomarkers that can precisely identify these populations are insufficient. In this context, a potential cold tumor microenvironment (TME) marker FARSB was investigated to reveal its impact on TME and patients' response to immunotherapy across pan-cancer. METHODS: The expression levels and mutational landscape of FARSB in pan-cancer were investigated. Kaplan-Meier and univariate Cox regression analyses were applied to analyze the prognostic significance of FARSB. Pathways affected by FARSB were investigated by gene set enrichment and variation analysis. The relationship between FARSB expression and immune infiltration was examined using the TIMER2 and R packages. Single-cell RNA sequencing (scRNA-seq) data of several cancer types from GSE72056, GSE131907, GSE132465, GSE125449 and PMID32561858 were analyzed to validate the impact of FARSB on the TME. The predictive effect of FARSB on immunotherapy efficacy was explored in 3 immune checkpoint inhibitors (ICIs)- treated cohorts (PMID32472114, GSE176307, and Riaz2017). RESULTS: FARSB expression was significantly higher in 25 tumor tissues than in normal tissues and was associated with poor prognosis in almost all tumor types. FARSB expression exhibited a strong association with several DNA damage repair pathways and was significantly associated with TP53 mutation in lung adenocarcinoma (P < 0.0001, OR=2.25). FARSB characterized a typical immune desert TME and correlated with impaired expression of chemokines and chemokines receptors. Large-scale scRNA-seq analysis confirmed the immunosuppressive role of FARSB and revealed that FARSB potentially shapes the cold TME by impeding intercellular interactions. In 3 ICI-treated cohorts, FARSB demonstrated predictive value for immunotherapy. CONCLUSION This study provides a pan-cancer landscape of the FARSB gene by integrated single-cell and bulk DNA sequencing analysis and elucidates its biological function to promote DNA damage repair and construct the immune desert TME, suggesting the potential value of FARSB as a novel marker for stratifying patients with poor immunotherapeutic benefits and "cold" TME.
Humans ; Tumor Microenvironment ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Sequence Analysis, RNA

Remote pharmaceutical care refers to the process that pharmacists provide pharmaceutical care to patients remotely through information technology. Remote pharmaceutical care in China starts late and develops slowly. Therefore ，this paper discusses the pharmaceutical care modes that pharmacists at home and abroad can provide under the remote mode by collecting literature. The results show that foreign remote pharmaceutical care starts early and is relatively mature. The service mainly included remote follow-up and intervention ，24-hour online prescription and order review ，24-hour online drug reorganization ，and guidance on rational drug use in remote areas or community hospitals. The service population covers patients with cardiovascular disease ， diabetes，asthma，AIDS and so on. Some hospitals have established an integrated pharmaceutical care system of “Internet+Medical Consortium”in China ，with which pharmacists can provide patients with pharmaceutical care such as remote follow-up and intervention，drug consultation and so on. With the promotion of telemedicine ，domestic pharmacists can gradually expand the scope of services ，expand pharmaceutical services such as remote consultation and remote popular science push ，and realize the sharing of high-quality pharmaceutical care for the whole people.

Objective: To analyze the risk factors of cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy. Methods: 530 patients with esophageal cancer underwent thoracoscopic-lapacoscopic esophagectomy at the Cancer Hospital, Chinese Academy of Medical Sciences from Jan 2011 to Dec 2015. The demographic, surgical and clinical data of patients were retrospectively analyzed. Multivariate logistic regression was used to evaluate risk factors of cervical anastomotic leakage in these patients. Results: A total of 530 patients undergoing thoracoscopic-lapacoscopic esophagectomy were enrolled in this study. There were 421 males and 109 females. The mean age was (59.40±8.08) years old, and 91 patients with cervical anastomotic leakage. Sigle factor analysis revealed that the risk grading by American Society of Aneshesiologists, previous history of chest surgery, respiratory comorbidity, diffusion capacity for carbon monoxide of the lung, operation time, anastomosis, average days of postoperative hospitalization, death within 30 days after surgery, respiratory complications, pleural effusion or empyema, and poor healing of the incision were statistically associated with cervical anastomotic leakage (all P<0.05). Multivariate analysis showed that previous history of chest surgery, hepatic insufficiency, manual anastomosis, prolonged postoperative hospitalization, and poor healing of the incision were independent risk factors for cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy (all P<0.05). Conclusions Previous history of chest surgery, hepatic insufficiency, poor healing of the incision, manual anastomosis and prolonged postoperative hospitalization were significantly associated with cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy. It′s important to strengthen perioperative nursing and surgical techniques to prevent anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy.