[Initial experience of transcatheter edge-to-edge repair guided by only transesophageal echocardiography in the treatment of tricuspid insufficiency].

Objective: To evaluate the feasibility and safety of transcatheter tricuspid valve edge-to-edge repair guided by only transesophageal echocardiography (TEE). Methods: Patients with severe tricuspid regurgitation in Fuwai Yunnan Cardiovascular Hospital who met the inclusion criteria based on clinical and echocardiographic evaluationand underwent transcatheter tricuspid valve edge-to-edge repair between January 2022 and May 2023 were prospectively enrolled. The procedure was performed under general anesthesia with endotracheal intubation and solely guided by TEE. The patients underwent clinical evaluation, electrocardiogram and transthoracic echocardiography one month after the procedure. Results: A total of 22 patients (12 males and 10 females) were included, with an average age of (71.3±6.7) years. All 22 patients successfully underwent the transcatheter tricuspid valve edge-to-edge repair under TEE guidance, with an average of (1.5±0.6) clips implanted. Immediately after procedure, six patients had no or trace regurgitation, 15 patients had mild regurgitation, and one patient had moderate regurgitation. All 22 patients completed 30-day follow-up, with four patients having trace regurgitation, 17 patients having mild regurgitation, and one patient having moderate regurgitation. Echocardiographic measurements revealed that effective regurgitant orifice area, regurgitant volume, vena contracta width, and proximal isovelocity surface area radius significantly decreased after the procedure (all P<0.05). In addition, inferior vena cava width, right atrial volume, tricuspid annular diameter, and right ventricular end-diastolic diameter significantly improved (all P<0.05), but tricuspid annular plane systolic excursion and right ventricular fractional area change did not show significant differences compared with those before the procedure (both P>0.05). Conclusion: It has been preliminarily confirmed that transcatheter tricuspid valve edge-to-edge repair solely guided by TEE is feasible and safe, but requires more large-scale studies for further validation.

[Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis].

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

[Effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation].

Objective: To investigate the effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation. Methods: This is a retrospective cohort study. The clinical data of 399 patients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Nanjing Medical University from January 2016 to September 2020 were retrospectively collected. There were 319 males and 80 females, aged (50.9±10.2) years (range: 10 to 73 years). These patients were divided into the control group (369 cases) and the dexmedetomidine group (30 cases) according to whether dexmedetomidine was continuously pumped intravenously during the operation until the operation ended. The 1∶2 propensity score matching was used to match the preoperative and intraoperative conditions of the two groups of patients, and the caliper width was 0.2. Outcome indicators included intraoperative postreperfusion syndrome, acute kidney injury and pulmonary complications within 7 days after surgery, length of hospital stay, time of stay in ICU, duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival and recurrence-free survival rate after surgery. The independent sample t test, χ2 test, Mann-Whitney U test or Fisher exact test was used to statistically analyze the data of the two groups of patients, respectively. Survival curves of overall survival and disease-free-survival were plotted by Kaplan-Meier method, and the survival rate and recurrence-free survival rate were compared by Log-rank test. Results: A total of 78 patients were included after propensity score matching, including 26 in the dexmedetomidine group and 52 in the control group. The incidence of acute kidney injury in the dexmedetomidine group within 7 days after surgery was 0 (0/26), significantly lower than that of the control group (21.2%,11/52)(corrected χ2=4.776, P=0.029). There were no significant differences in the incidence of intraoperative postreperfusion syndrome and pulmonary complications within 7 days after surgery, length of hospital stay, ICU time, the duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival, and recurrence-free survival rate after surgery between the two groups (all P>0.05). Conclusion: Continuous infusion of dexmedetomidine via intravenous pump during operation may be beneficial in reducing the incidence of acute kidney injury within 7 days after orthotopic liver transplantation.

IL-37 alleviates intervertebral disc degeneration via the IL-1R8/NF-κB pathway.

OBJECTIVE: Intervertebral disc degeneration (IDD) has been reported to be a major cause of low back pain (LBP). Interleukin (IL)-37 is an anti-inflammatory cytokine of the interleukin-1 family, which exerts salutary physiological effects. In this study, we assessed the protective effect of IL-37 on IDD progression and its underlying mechanisms. METHODS: Immunofluorescence (IF) was conducted to measure IL-37 expression in nucleus pulposus tissues. CCK-8 assay and Edu staining were used to examine the vitality of IL-37-treated nucleus pulposus cells (NPCs). Western blot, qPCR, ELISA as well as immunohistochemistry were used to assess senescence associated secreted phenotype (SASP) factors expression; and NF-κB pathway was evaluated by western blot and IF; while IL-1R8 knock-down by siRNAs was performed to ascertain its significance in the senescence phenotype modulated by IL-37. The therapeutic effect of IL-37 on IDD were evaluated in puncture-induced rat model using X-ray, Hematoxylin-Eosin, Safranin O-Fast Green (SO), and alcian blue staining. RESULTS: We found IL-37 expression decreased in the IDD process. In vitro, IL-37 suppressed SASP factors level and senescence phenotype in IL-1ß treated NPCs. In vivo, IL-37 alleviated the IDD progression in the puncture-induced rat model. Mechanistic studies demonstrated that IL-37 inhibited IDD progression by downregulating NF-κB pathway activation in NPCs by activating IL-1R8. CONCLUSION: The present study suggests that IL-37 delays the IDD development through the IL-1R8/NF-κB pathway, which suggests IL-37 as a promising novel target for IDD therapy.

[Efficacy and safety of new systemic therapies in moderate-to-severe atopic dermatitis in the elderly: meta-analysis].

Objective: To systematically evaluate the efficacy and safety of new systemic therapies (biological agents and JAK inhibitors) in moderate-to-severe elderly atopic dermatitis. Methods: The database of Embase, PubMed, Web of Science,Cochrane, the Global Resource of Eczema Trials database, ClinicalTrials. Gov, CNKI, Wanfang, VIP were used to search for literatures of randomized controlled trials (RCTs) and real-world studies of the treatment of moderate-to-severe AD with the new systemic therapies from January 2014 to February 2023. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias included in the study. Data were analyzed by Review Manager 5.3 software for meta-analysis and odds ratio (OR) and 95% confidence interval were used as the effect statistics. The heterogeneity and publication bias were assessed. Results: A total of five studies (523 elderly patients and 802 young patients) using dupilumab were included for meta-analysis. Dupilumab showed good efficacy in elderly AD, with 74.6%(390/523) of patients whose EASI reached 75, which there was no significant difference with young patients (OR=0.79, 95%CI:0.58-1.07, P=0.122); the proportion of elderly patients with NRS improvement≥4 was 68.7%(244/355), and there was no significant difference with young patients (OR=0.79, 95%CI:0.55-1.14, P=0.213). The most common adverse reactions were conjunctivitis, facial and neck erythema and injection site reactions, and there are no serious adverse events in both groups. The incidence of adverse events in elderly patients was 24.3%(65/267), which was not significantly different from that in young patients (OR=1.07, 95%CI:0.65-1.77, P=0.789). There are few studies on other biological agents and JAK inhibitors in elderly AD patients. We only found 4 studies of elderly AD patients using JAK inhibitors (2 studies on abrocitinib and 2 studies on upadacitinib). The clinical efficacy of abrocitinib in the elderly was not significantly different from that in the young. The incidence of serious adverse events of abrocitinib and upadacitinib increased in the elderly and was dose-related. Conclusion: The efficacy and safety of dupilumab in elderly AD patients were similar to those in the young patients, and the JAK inhibitor needs to be further studied and verified.

[Application value of image fusion technology in transcatheter aortic valve implantation].

Objective: To analysis the application value of image fusion technology in transcatheter aortic valve implantation (TAVI). Methods: A total of 35 patients underwent trans-femoral TAVI using the first-generation VENUS-A valve in Heart Center of Henan Provincial People's Hospital from January 2020 to May 2021 were analyzed retrospectively. Among them, there were 21 males and 14 females, aged from 64 to 81 years, with a mean (SD) of (71.37±5.66) years. They were divided into conventional group (n=22) and fusion group (n=13), according to whether image fusion technology was used during operation. The preoperative general data, intraoperative data, differences of postoperative renal function and residence time in intensive care unit (ICU) were analyzed and compared between the two groups. The postoperative echocardiography and 12 lead ECG were observed. Results: All 35 patients in this study were with severe aortic stenosis, of which, 10 patients were complicated with moderate to severe regurgitation. Compared with the conventional group, the intraoperative fusion group had fewer angiography times [3.0 (3.0, 4.0) vs 5.0 (5.0, 6.0)], X-ray absorbed dose [342.0 (44.5) mGy vs 388.4 (71.0) mGy], and contrast dosage [(73.5±10.5) ml vs (90.3±10.3) ml], and shorter rapid pacing time [(14.0±1.6) seconds vs (16.5±2.0) seconds] (all P<0.05). There was no significant differences in X-ray irradiation time, operation time, sizing of the pre-dilated balloon, valve implantation depth and other indicators (all P>0.05). There was no significant differences in ICU retention time and postoperative renal function (all P>0.05). Postoperative echocardiography showed that the function of aortic valve was good, with mild perivalvular leakage in 2 cases in the conventional group and 1 case in the fusion group; and one patient was implanted with permanent pacemaker after TAVI in the conventional group. Conclusion: Image fusion technology simplifies the TAVI process, shortens the ventricular pacing time and reduces the dosage of X-ray and contrast, and has certain clinical application value.

[Long-term mortality risk of valvular heart disease adults over 35 years old in Chinese communities].

Objective: To investigate the risk and influencing factors of long-term mortality of valvular heart disease (VHD) adults aged 35 years and over in Chinese communities. Methods: A cohort study was carried out. The data of the subjects who underwent echocardiography were collected from the Chinese Hypertension Survey between 2012 and 2015 and survival outcomes were followed up between 2018 and 2019. Kaplan-Meier survival curves were plotted and compared using log-rank test. Cox proportional hazards models were used to analyze the influence of VHD on mortality. Results: During an average follow-up time of (4.6±0.9) years, a total of 23 237 participants (10 881 males and 12 356 females) were pooled into the final analysis from 5 eastern, 5 central, and 4 western provinces, cities and autonomous regions in China, with a mean age of (56.9±13.2) years. Among the included participants, 1 004 had VHD (467 males and 537 females), with a mean age was of (68.1±12.6) years. In the Kaplan-Meier analysis, participants with VHD had a significantly increased risk of all-cause mortality (log-rank χ2=351.82, P<0.001) and cardiovascular mortality (log-rank χ2=284.14, P<0.001) compared with those without VHD. Multivariate Cox regression analysis showed that compared with those without VHD, the participants with rheumatic VHD had a 45% increased risk of all-cause mortality (HR=1.45, 95%CI: 1.12-1.89) and degenerative VHD increased the risk of cardiovascular mortality by 69% (HR=1.69, 95%CI: 1.19-2.38). The risk factors of cardiovascular mortality for VHD were age 55 years and over (55-<75 years: HR=4.93, 95%CI: 1.17-20.85;≥75 years: HR=11.92, 95%CI: 2.85-49.80) and diabetes mellitus (HR=1.71, 95%CI: 1.00-2.93). Conclusions: VHD is a risk factor of all-cause mortality and cardiovascular mortality among adults aged 35 years and over. Age 55 years and over and diabetes mellitus are adverse prognostic factors for patients with VHD.

[Genetic diagnosis of microcephaly].

Objective: To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. Methods: A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. Results: In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. Conclusions: CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.

[Analysis of the epidemiological characteristics of scarlet fever in Yantai City, Shandong Province from 2015 to 2019].

From 2015 to 2019, the annual average incidence rate of scarlet fever was 7.80/100 000 in Yantai City, which showed an increasing trend since 2017 (χ2trend=233.59, P<0.001). The peak period of this disease was from April to July and November to January of the next year. The ratio of male to female was 1.49∶1, with a higher prevalence among cases aged 3 to 9 years (2 357/2 552, 92.36%). Children in kindergartens, primary and middle school students, and scattered children were the high risk population, with the incidence rate of 159.86/100 000, 25.57/100 000 and 26.77/100 000, respectively. The global spatial auto-correlation analysis showed that the global Moran's I index of the reported incidence rate of scarlet fever in Yantai from 2015 to 2019 was 0.28, 0.29, 0.44, 0.48, and 0.22, respectively (all P values<0.05), suggesting that the incidence rate of scarlet fever in Yantai from 2015 to 2019 was spatial clustering. The local spatial auto-correlation analysis showed that the "high-high" clustering areas were mainly located in Laizhou City, Zhifu District, Haiyang City, Fushan District and Kaifa District, while the "low-high" clustering areas were mainly located in Haiyang City and Fushan District.

[Enlightening from optimizing post-authorization safety monitoring system of SARS-CoV-2 vaccines in major economies worldwide].

Ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the unprecedented rapid development and large-scale rolling out of different platform-based COVID-19 vaccines worldwide. How to effectively respond to the expected scale increasing adverse events after vaccination campaign of COVID-19 vaccines is a common problem faced by the world. A lot of countries and regions around the world have arranged in advance at different levels, optimizing the original vaccine safety monitoring system from the perspectives of strengthening the foundation and capabilities, promoting internal and external cooperation, upgrading methods, as well as improving transparency and public communication, which has ensured the good and efficient operation of the system and can provide reference for the construction of relevant fields in China.