Glucagon-like peptide 1 receptor is a T cell-negative costimulatory molecule.

Glucagon-like peptide-1 receptor (GLP-1R) is a key regulator of glucose metabolism known to be expressed by pancreatic ß cells. We herein investigated the role of GLP-1R on T lymphocytes during immune response. Our data showed that a subset of T lymphocytes expresses GLP-1R, which is upregulated during alloimmune response, similarly to PD-1. When mice received islet or cardiac allotransplantation, an expansion of GLP-1Rpos T cells occurred in the spleen and was found to infiltrate the graft. Additional single-cell RNA sequencing (scRNA-seq) analysis conducted on GLP-1Rpos and GLP-1Rneg CD3+ T cells unveiled the existence of molecular and functional dissimilarities between both subpopulations, as the GLP-1Rpos are mainly composed of exhausted CD8 T cells. GLP-1R acts as a T cell-negative costimulatory molecule, and GLP-1R signaling prolongs allograft survival, mitigates alloimmune response, and reduces T lymphocyte graft infiltration. Notably, GLP-1R antagonism triggered anti-tumor immunity when tested in a preclinical mouse model of colorectal cancer.

Accurate diagnosis and effective treatment of abnormal meridians in erectile dysfunction patients based on infrared thermography: an electrophysiological technique study.

An increasing body of research has demonstrated that appropriate stimulation of the meridians and acupoints in the human body can play a preventative and therapeutic role in diseases. This study combines the use of infrared thermography with intelligent electrophysiological diagnostic system (iEDS) to accurately diagnose and apply transdermal low-frequency electrical stimulation to treat abnormal meridians in patients with erectile dysfunction (ED). The treatment protocol included 6 treatments (each lasting 30 min and performed twice a week). The International Index of Erectile Function-5 (IIEF-5), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Erection Hardness Scale were used to assess treatment results. A total of 62 patients were included in this study, with 31 patients in the treatment group and 31 patients in the sham therapy group. After six treatments, the treatment group improved significantly in IIEF-5 (15.52 ± 2.06 vs. 18.84 ± 2.67, p < 0.001), PHQ-9 (8.32 ± 6.33 vs. 4.87 ± 4.41, p < 0.001), GAD-7 (5.32 ± 5.08 vs. 2.94 ± 3.31, p = 0.003), and EHS (2.48 (2.00, 3.00) vs. 2.90 (2.00, 3.00), p = 0.007). After six sham treatment sessions, no improvements in any of the scores were reported in the sham therapy group. Following that, this group had an additional six treatments of regular therapy, which resulted in statistically significant improvements in IIEF-5 (16.65 ± 1.96 VS. 19.16 ± 2.40, p < 0.001), PHQ-9 (8.81 ± 6.25 VS. 4.97 ± 4.36, p < 0.001), GAD-7 (5.74 ± 5.18 VS. 3.68 ± 3.42, p < 0.001), and EHS (2.61 (2.00, 3.00) VS. 3.03 (2.00, 4.00), p = 0.003). No adverse events were reported regarding penile discomfort, pain, injury, or deformity. CLINICAL TRIALS: The study protocol is registered in the Clinical Trials Registry with the identification number ChiCTR2300070262.

Experimental study of the response of articular cartilage surface roughness to load / 生物医学工程学杂志

Cartilage surface fibrosis is an early sign of osteoarthritis and cartilage surface damage is closely related to load. The purpose of this study was to study the relationship between cartilage surface roughness and load. By applying impact, compression and fatigue loads on fresh porcine articular cartilage, the rough value of cartilage surface was measured at an interval of 10 min each time and the change rule of roughness before and after loading was obtained. It was found that the load increased the roughness of cartilage surface and the increased value was related to the load size. The time of roughness returning to the initial condition was related to the load type and the load size. The impact load had the greatest influence on the roughness of cartilage surface, followed by the severe fatigue load, compression load and mild fatigue load. This article provides reference data for revealing the pathogenesis of early osteoarthritis and preventing and treating articular cartilage diseases.

Drug repurposing against coronavirus disease 2019 (COVID-19):A review / 药物分析学报

Since December 2019,severe acute respiratory syndrome coronavirus 2 has been found to be the culprit in the coronavirus disease 2019 (COVID-19),causing a global pandemic.Despite the existence of many vaccine programs,the number of confirmed cases and fatalities due to COVID-19 is still increasing.Furthermore,a number of variants have been reported.Because of the absence of approved anti-coronavirus drugs,the treatment and management of COVID-19 has become a global challenge.Under these circumstances,drug repurposing is an effective method to identify candidate drugs with a shorter cycle of clinical trials.Here,we summarize the current status of the application of drug repurposing in COVID-19,including drug repurposing based on virtual computer screening,network pharmacology,and bioactivity,which may be a beneficial COVID-19 treatment.

Design and application of bundle treatment plan in the early stage for severe human infection by avian influenza H7N9 / 中华危重病急救医学

Objective To design bundle treatment plan in the early stage for severe human infection by avian influenza H7N9, and explore its clinical efficacy and application value. Methods Fifteen patients with severe human infection by avian influenza H7N9 in Guizhou Province from December 29th, 2016 to June 7th, 2017 were enrolled. Patients admitted from March 6th, 2017 to June 7th, 2017 served as a prospective observation period (bundle treatment group), and those from December 29th, 2016 to March 5th, 2017 were selected as a historical control period (conventional treatment group). Conventional treatment group was given conventional treatment such as isolation, anti-virus, symptomatic treatment, and traditional Chinese medicine and so on. Bundle treatment group was given bundle treatment on the basis of conventional treatment, including isolation, anti-virus, respiratory support, restrictive fluid management, immunotherapy, inhibition of inflammation, antibiotic therapy, nutritional support, prevention of hospital acquired infection (HAP), individual sedation, continuous blood purification (CBP) for acute kidney injury (AKI) and severe acute respiratory distress syndrome (ARDS) patients, and intensive care. A cluster of bundle treatment team was set up to ensure that all measures carried out smoothly. The gender, age, onset to diagnosis time, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, oxygenation index (PaO2/FiO2) at admission, the length of intensive care unit (ICU) stay, total hospitalization time and prognosis of the two groups were observed. Correlation analysis between bundle therapy and prognosis was analyzed by Spearman correlation analysis. Receiver operating characteristic (ROC) curve was drawn, and the clinical value of bundle treatment was analyzed. Results There was no significant difference in gender, age, onset to diagnosis time, APACHEⅡscore, PaO2/FiO2, the length of ICU stay, or total hospitalization time between bundle treatment group (n = 9) and conventional treatment group (n = 6), but the death patients in the bundle treatment group was significantly fewer than those in conventional treatment group (cases:2 vs. 5, χ2= 3.225, P = 0.041). Correlation analysis showed that there was a significant correlation between the mortality and whether received bundle treatment or not in patients who infected by avian influenza H7N9 (r = -0.875, P = 0.018). ROC curve analysis showed that the area under the ROC curve (AUC) of non-bundle treatment for predicting the death in patients with severe human infection by avian influenza H7N9 was 0.938, 95% confidence interval (95%CI) was 0.795-1.000, the sensitivity was 88.88%, and the specificity was 98.62%. Conclusions Early bundle therapy has a significant effect on severe human infection by avian influenza H7N9, which can improve the prognosis and reduce the mortality of patients. It is worthy for clinical application.