Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

BACKGROUND:In clinical work,the stiffness of neck soft tissue in patients with neck and shoulder pain is mainly detected through palpation,which is highly subjective and lacks an objective basis.Real-time shear wave elastography is a quantitative elastic ultrasound technique that can objectively assess muscle elasticity and muscle status. OBJECTIVE:To apply real-time shear wave elastography to assess the stiffness of scalene muscles in patients with neck and shoulder pain and to observe the characteristics of muscle stiffness changes in the bilateral anterior,middle and posterior scalene muscles in patients with neck and shoulder pain. METHODS:From December 2021 to June 2022,36 healthy subjects(control group)and 36 patients with neck and shoulder pain(test group)were recruited at the Shenzhen Hospital of Guangzhou University of Chinese Medicine.Real-time shear wave elastography was applied to measure the mean values of elastic modulus and cross-sectional area of the anterior and middle and posterior scalene muscles bilaterally in the neutral and lateral flexion positions of the neck in both groups. RESULTS AND CONCLUSION:In the same position,there were no significant differences between the mean Values of elastic modulus of the left and right anterior scalene muscles as well as between the mean Values of elastic modulus of the left and right middle scalene muscles in each group(P>0.05);there were no significant differences between the cross-sectional area of the left and right anterior scalene muscles as well as the cross-sectional area of the left and right posteromedial scalene muscles in each group(P>0.05);and the elastic modulus and cross-sectional area of the posteromedial scalene muscles were significantly higher than those of the anterior scalene muscles in both groups(P<0.01,P<0.001).The mean Values of elastic modulus of the anterior and posteromedial scalene muscles were higher in the test group than in the control group in the neutral and lateral neck flexion positions(P<0.001),while the cross-sectional areas of the anterior and posteromedial scalene muscles were lower than those in the control group(P<0.01,P<0.001).To conclude,real-time shear wave elastography can be used to visually evaluate the differences in the mean Values of elastic modulus of the anterior and posteromedial scalene muscles in different states of the neck muscles in patients with neck and shoulder pain,whose bilateral scalene muscles are in a state of strain and stiffness.

Objectives:To evaluate the valvular and cardiac function,cardiac reverse remodeling at 6-month after transcatheter edge-to-edge repair(TEER)for patients with functional and degenerative mitral valve regurgitation,and summarize the experience of echocardiography application. Methods:The clinical data of 93 patients with moderate to severe mitral regurgitation(MR)treated with TEER and completed 6-month follow-up in Yunnan Fuwai Cardiovascular Hospital from July 2022 to February 2023 were retrospectively analyzed.Patients were divided into functional mitral regurgitation(FMR)and degenerative mitral regurgitation(DMR)groups according to MR etiology.The valve characteristic parameters,as well as valvular function,chamber volume and cardiac functional parameters before and at 6 months after operation were compared.The key points of echocardiography application were summarized. Results:Among all patients,71 were FMR and 22 were DMR.There were differences in valve structure between the two groups.Mitral TEER were successfully accomplished and all patients completed 6-month follow-up.The key points of echocardiography application included:valve structure analysis,atrial septal puncture location,device delivery process monitoring and image optimization during clamping process.The mitral regurgitation grade and NYHA grade were significantly improved in all patients at 6 months after TEER(P<0.05),and the mean mitral valve pressure gradient was higher than that before operation(P<0.05).Left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV)and left atrial volume index in FMR group were significantly decreased(P<0.05),while left ventricular and left atrial volume in DMR group remained unchanged(P>0.05).There were no significant changes in left ventricular ejection fraction and left ventricular global strain in both groups during the observation period(P>0.05).The changes of LVEDV and LVESV before and after operation were more significant in FMR group than those in DMR group(P<0.05). Conclusions:Mitral TEER can reduce the degree of regurgitation and improve cardiac function in the early postoperative period for moderate and severe MR patients with different etiologies.There are differences in preoperative valve structure and postoperative cardiac reverse remodeling between FMR and DMR patients.Echocardiography is an important imaging technique for the evaluation and monitoring process before,during and post mitral TEER.

We report the first in man experience of robotic assisted transcatheter edge-to-edge repair(TEER)with pure Trans-esophageal echocardiography-guidance.A 55y female was diagnosed with heart failure with 4+functional MR despite optimal medical treatment.TEER procedure was planned with robotic assistance.After guiding catheter,the robotic system was incorporated into the TEER device to replace manual operation.Under pure echo-guidance one clip was successfully placed in A2/P2 region with marked reduction of MR to 1+.Patient was discharged without complication.

The present case report described a patient with paroxysmal atrial fibrillation who received pulsed-filed ablation guided by intracardiac echocardiography and 3-dimentional mapping system.All four pulmonary veins were isolated in the procedure,good clinical results and acute safety profile were achieved.The present case reveals the safety and feasibility of the technique for the treatment of paroxysmal atrial fibrillation.

Objective    To investigate the early clinical results of MitraClip system in domestic patients. Methods     We retrospectively analyzed the clinical data of 36 patients who underwent transcatheter edge-to-edge repair procedure using MitraClip system in Beijing Fuwai Hospital, Shenzhen Fuwai Hospital and Fuwai Yunnan Cardiovascular Hospital between January and June 2021. There were 24 males and 12 females, with a median age of 70 (47-86) years. Ten (27.8%) patients had 3+ mitral regurgitation (MR) and 26 (72.2%) patients had 4+ MR preoperatively. Results    All procedures were successfully performed. The reduction in MR was 2+ at least immediately after surgery, and 91.7% of patients had MR≤2+ at 3 days postoperatively. There was no statistical difference in left ventricular ejection fraction change postoperatively. Forward velocity and peak gradient of mitral valve were increased after the procedure. Mean gradient of mitral valve were increased at 3 days postoperatively than immediately after surgery (P<0.001). Two patients had acute pericardial effusion intraoperatively, and received pericardial puncture and drainage immediately. Conclusion    MitraClip system has been applied well in domestic patients and can significantly improve MR. This sutdy has a good consistency with foreign studies, and the early results are satisfactory.

Mitral regurgitation (MR) is the most common valvular heart disease, however, majority of patients are not suitable for open heart surgery due to comorbidity such as organ and heart dysfunction. Transcatheter edge-to-edge mitral valve repair has become an effective treatment option for high-risk patients with MR. Two patients were enrolled in this study inlcuding one 60-year degenerative mitral regurgitation patient and one 72-year functional mitral regurgitation patient. Transcatheter repair procedure was successfully done for the two patients without postoperative complication.

Objective:To examine the relationship between pre-pregnancy BMI, gestational diabetes (GDM) and different indicators of childhood obesity at the age of 4.Methods:Based on Ma’anshan Birth Cohort Study, singleton children who were born in Ma’anshan of Anhui province from October 2013 to April 2015, were followed for 4 years, consecutively. During the first questionnaire survey, data including pre-pregnancy weight, height and socio-demography were collected. During 24-28 week of gestation, 75 g oral glucose tolerance test was conducted for them. Childhood height, weight, waist circumference and body composition were measured at the age of 4. Comparisons between groups were performed using chi-square test, analysis of variance or t-test. The relationship between pre-pregnancy overweight/obesity, GDM and childhood obesity-related characteristics were analyzed by logistic regression model and generalized linear model analysis. Results:The prevalence rates of overweight and obesity in children at the age of 4 were 13.08% and 6.03%, respectively. After adjustment for characteristics related to mothers and their children, significantly increased risk of obesity ( OR=3.27, 95% CI: 2.15-4.98), larger waist circumference ( OR=2.32, 95% CI: 1.72-3.14) and higher waist-to-weight ratio ( OR=2.29, 95% CI: 1.73-3.02) were seen in the offspring of women with pre-pregnancy overweight/obesity. Body composition (skeletal muscle, body fat, body fat percentage) of the offspring were strongly correlated with pre-pregnancy overweight/obesity of the mothers ( P<0.05). Maternal GDM was associated with higher risk of childhood obesity ( OR=1.78, 95% CI: 1.14-2.79), on mothers without GDM during pregnancy. However, neither larger waist circumference, or higher waist-to-weight ratio seemed to increase the risk. Moreover, maternal GDM was not associated with body composition measures (skeletal muscle, body fat, body fat percentage). Conclusion:Pre-pregnancy BMI and maternal GDM were independent risk factors for obesity in 4-year-old children, and pre-pregnancy BMI was correlated with various indicators of body composition in children.

Adult ; Aged ; Aged, 80 and over ; Carrier Proteins ; metabolism ; Female ; Humans ; Inflammasomes ; metabolism ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein

OBJECTIVE: To investigate the clinical features and therapeutic effects of sudden deafness after radiotherapy combined with chemotherapy in nasopharyngeal carcinoma patients. METHOD: Clinical data of 42 nasopharyngeal carcinoma patients suffered from sudden deafness after radiotherapy combined with chemotherapy were analyzed retrospectively. Among the 42 patients, 2 showed moderate deafness, 4 presented excessive deafness, 30 suffered from severe deafness, and 6 exhibited profound deafness. The audiogram pattern of 33 patients met with the type of high tone frequencies hearing loss, and that of the rest 9 cases showed hearing loss at all frequencies. All patients received medical therapy combined with hyperbaric oxygen therapy. RESULT: Of all the cases with hearing loss, 2 were cured, 2 showed excellent recovery, 9 came out partial recovery, and 29 showed no response to the treatment. The total effective rate was 30.95%. For the accompanied symptoms, none of the 30 cases of tinnitus were relieved, 3 out of 10 cases of aural fullness were cured, and the 5 cases of dizziness or vertigo were all improved. CONCLUSION The sudden deafness after radiotherapy combined with chemotherapy in patients with nasopharyngeal carcinoma is closely related to radiotherapy. The hearing loss is serious, and the therapeutic effects are not satisfactory.
Antineoplastic Agents ; adverse effects ; Carcinoma ; Dizziness ; etiology ; therapy ; Hearing Loss, High-Frequency ; etiology ; therapy ; Hearing Loss, Sudden ; etiology ; therapy ; Hearing Tests ; Humans ; Hyperbaric Oxygenation ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Radiotherapy ; adverse effects ; Retrospective Studies ; Tinnitus ; etiology ; therapy ; Vertigo ; etiology ; therapy