OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

Transcatheter tricuspid valve intervention is the new frontier of interventional cardiology. The LuX-Valve is a radial force-independent orthotopic tricuspid valve replacement device developed in China. The LuX-Valve Plus transcatheter tricuspid valve replacement (TTVR) system is changed from the trans-atrial to the transjugular approach, which further reduces trauma and pulmonary complications compared with the first generation LuX-Valve. The first-in-human study has been completed at Zhongshan Hospital, Fudan University and an exploratory multicentre clinical study is underway. Echocardiography plays an important role in pre-TTVR screening, intraoperative guidance and postoperative evaluation and follow-up, especially two-dimensional transoesophageal echocardiography (2D-TEE) and three-dimensional transoesophageal echocardiography (3D-TEE). However, there is a lack of appropriate intraoperative guidance and assessment protocols. In this study, we briefly described the protocols and imaging considerations for intraoperative 2D-TEE and 3D-TEE to ensure the successful implantation of TTVR.

BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-12003513.
Humans ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Myocardial Infarction/complications* ; Stroke/epidemiology*

Tricuspid regurgitation (TR) interventions are under rapid development. The K-Clip? system is the first domestic transcatheter tricuspid annuloplasty system with unique clamping procedure to achieve annular reduction.Intraoperative echocardiographic monitoring procedures for transcatheter tricuspid annuloplasty have not been reported yet in China. Thus, this review aimed to propose the standard two-dimensional and three-dimensional transesophageal echocardiographic workplanes and procedures to guide and monitor the implantation of K-Clip system based on our experience in Zhongshan Hospital, Fudan University to provide a reference point for the intraoperative echocardiographic monitoring of future transcatheter tricuspid annuloplasty devices in China.

Cardiovascular disease is a leading cause of death among the elderly and the incidence of coronary artery disease progressively increases with advancing age.Traditional risk factors are incompletely predictive of cardiovascular disease development.With the advent of high-throughput next-generation genome sequencing technologies in recent years, some studies have indicated that aging is associated with an increased frequency of somatic mutations of hematological neoplasm-related genes in the hematopoietic system, providing a competitive growth advantage for mutant hematopoietic cells and thus allowing for their clonal expansion, a phenomenon known as clonal hematopoiesis of indeterminate potential(CHIP). CHIP is common in middle-aged and elderly populations and is associated with increased risks of hematological cancer and all-cause death.There is growing evidence that CHIP is involved in the development and progression of multiple cardiovascular disorders through the activation of inflammatory responses.In this review, we will give an overview of current advances in the understanding of clonal hematopoiesis in cardiovascular disease.

Photoimmunotherapy (PIT) is an emerging tumor-targeted phototherapy that combines the tumor specificity of monoclonal antibodies with the phototoxicity of light absorbers to rapidly and selectively induce the immunogenic death of target tumor cells. PIT has minimal side effects due to its high specificity. The immunogenic cell death induced by PIT results in rapid maturation of immature dendritic cells proximal to dying tumor cells. Subsequently, the mature dendritic cells present the tumor antigens to CD8+ T cells and induce their activation and proliferation, thus enhancing the antitumor immune response of the host. PIT can also improve the anticancer efficacy by enhancing the penetration of nanomedicines into tumor tissues. In view of the excellent application prospects of PIT, this review summarizes the advances in the immune activation mechanism of PIT, the superenhanced permeability and retention effect, and the new strategies for combinatory therapy, providing references for future research and clinical translation.
Antibodies, Monoclonal/therapeutic use* ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Photosensitizing Agents ; Phototherapy

Objective:To explore the correlation between the index of hemodynamics in perinatal period and retinopathy of prematurity(ROP), so as to provide basis for the better prevention and treatment of ROP.Methods:From May 2017 to April 2019, the preterm infants were admitted to the Neonatal Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University at birth and were hospitalized for more than 2 weeks, gestational age ≤ 35 weeks and birth weight ≤ 2 500 g. They were selected as the study objects.The perinatal data including heart rate, blood pressure, patent ductus arteriosus, ventricular septal defect, and NT-proBNP level on the 1 st, 7 th and 14 th day, respectively after birth were collected.They were divided into ROP group and non ROP group according to the results of the retinopathy screening report.The influencing factors of ROP were screened out by univariate analysis and multivariate regression analysis. Results:A total of 1 119 subjects were included, 105 infants with ROP were detected, and the prevalence of ROP was 9.4%.Among them, 12 cases of pre-threshold lesion type 1 and threshold lesions required treatment, accoun-ting for 1.07% of screened preterm infants .Univariate analysis and multivariate regression analysis revealed that gestational age, birth weight, total oxygen therapy time, and intrauterine growth restriction were all factors affecting ROP, and 2 hemodynamic related indicators, such as the level of NT-proBNP in plasma on the 14 th day after birth, and placenta previa or abruption were also related to ROP( OR=0.604, 0.647, 1.276, 2.361, 1.688 and 2.506, respectively, all P<0.05). Conclusion:The hemodynamic changes in perinatal period may be involved in the formation of ROP, and it is necessary to further clarify its mechanism.

Near infrared photoimmunotherapy (NIR-PIT) is a highly selective molecularly targeted phototherapy for cancer which is based on injecting a conjugate of IRDye700DX,a water-soluble near-infrared silicon-phthalocyanine dye,and a monoclonal antibody that targets an antigen on the cancer cell surface. Subsequent local irradiation of NIR light causes the rapid and specific tumor cell death. Due to the good clinical translation prospects of NIR-PIT,this paper summarizes the influencing factors,antitumor mechanism,main challenges and recent strategies,which may benefit for its research and clinical application.

Objective: To investigate the incremental value of coronary flow reserve (CFR) assessed by cadmium zinc telluride(CZT)-SPECT as an adjunct to myocardial perfusion imaging (MPI) in the diagnosis of coronary artery disease (CAD). Methods: Data of 132 patients (89 males, 43 females; 40-81 years) with or suspected with CAD who successfully underwent rest and stress MPI and CFR from November 2017 to October 2018 in Zhongshan Hospital Affiliated to Fudan University were retrospectively analyzed. Based on coronary angiography (CAG) as the " gold standard" , the value of MPI and MPI+ CFR in the diagnosis of CAD was evaluated and compared. χ² test or Fisher exact probability test was used for data analysis. Results: Of 132 patients, 61 (46.2%) were CAD with stenosis of at least 75% in one vessel (47.5%, 29/61), two vessels (34.4%, 21/61), or three vessels (18.0%, 11/61). A total of 104 (26.3%) vessels with stenosis of at least 75%, 25 (6.3%) vessels with stenosis of 65%-74%, and 30 (7.6%) vessels with stenosis of 50%-64% were found in 396 vessels. For detecting coronary stenosis of at least 75%, the sensitivity and accuracy of MPI on per-patient analysis were 86.89%(53/61) and 68.94%(91/132), which increased to 96.72%(59/61; χ²=3.921, P<0.05) and 87.88%(116/132; χ²=13.984, P<0.01) by MPI+ CFR. On per-vessel analysis, the sensitivity and accuracy of MPI were 72.12%(75/104) and 77.53%(307/396) and increased to 96.15%(100/104; χ²=22.511, P<0.01) and 85.10%(337/396; χ²=7.479, P<0.05) by MPI+ CFR. The sensitivity of MPI for predicting one, two, and three vessels disease were 72.41%(21/29), 42.86%(9/21), and 5/11 and were improved to 93.10%(27/29; χ²=4.350, P=0.037), 90.48%(19/21; χ²=10.714, P=0.001), and 11/11 (P=0.012) by MPI+ CFR. For coronary with stenosis of 65%-74%, the sensitivity of MPI was 24.00%(6/25) and was improved to 64.00%(16/25; χ²=8.117, P=0.004) by MPI+ CFR. For coronary with stenosis of 50%-64%, the sensitivity of MPI was 40.00%(12/30) and was improved to 76.67%(23/30; χ²=8.297, P=0.004) by MPI+ CFR. Conclusion As an adjunct to MPI, CFR can significantly improve the sensitivity and accuracy in the diagnosis of CAD, particularly for patients with mild stenosis and multivessel CAD.