Objective:To explore the potential causal relationships between major depressive disorder(MDD),anxiety disorder(AD)and various highly prevalent cancers from the genetic perspective.Methods:Sum-mary statistics from large-scale genome-wide association studies(GW AS)were analyzed using a bidirectional two-sample Mendelian randomization(MR)approach.The inverse variance weighting method(IVW)was usedas the main analytical approach.The intercept term of MR-Egger regression and the MR-PRESSO method were adopted for the pleiotropy test.Results:The IVW analysis revealed potential causal relationships between MDD and breast cancer[OR(95％CI):1.11(1.01-1.22),P＜0.05],AD and lung cancer[OR(95％CI):1.30(1.02-1.65),P＜0.05],and between colon cancer and MDD[OR(95％CI):1.05(1.00-1.11),P＜0.05].The results of the pleiotropy test showed that the intercept terms of the MR-Egger regression were not statistically significant,indica-ting the absence of pleiotropy.The MR-PRESSO method detected outliers only in the relationship between MDD and breast cancer.The association between MDD and breast cancer remained significant after correction for outliers[OR(95％CI):1.10(1.03-1.17),P＜0.05].Conclusion:The study suggests that MDD may be a risk factor for breast cancer,AD may increase the risk factor for lung cancer,and colon cancer may elevate the risk factor of MDD.Moreover,the possibility of reverse causal relationships has been excluded in all these cases.

One of its primary surgical treatments of tricuspid regurgitation is tricuspid valve biological valve replacement. Catheter tricuspid valve-in-valve implantation is a novel interventional alternative for biological valve failure. The non-invasive lung fluid measuring device remote dielectric sensing (ReDSTM) has been increasingly incorporated into clinical practice as a means of monitoring chronic heart failure in recent years. This report describes the process and outcomes of the first instance of perioperative lung fluid volume evaluation following transcatheter tricuspid valve implantation utilizing ReDSTM technology. The patient has a short-term, substantial increase in postoperative lung fluid volume as compared to baseline.

Objective To explore the clinical significance and to investigate the expression of TOMM40L in the tis-sue of triple-negative breast cancer(TNBC).Methods The expression of TOMM40L in TNBC tissues and normal tissues was analyzed with TCGA and UALCAN databases.Univariate and multivariate Cox regression analysis and Nomogram model were used to evaluate the prognostic value of TOMM40L in TNBC patients.Furthermore,the ex-pression of TOMM40L in breast cancer cell lines was evaluated using Western blot analysis and quantitative real-time PCR.Specific siRNA knockdown was performed to evaluate the migration,and cell proliferation of TOMM40L.The potential signaling pathways of TOMM40L were identified by GO and KEGG and GSEA.Results TOMM40L was highly expressed in the TNBC compared to non-TNBC tumor tissues(P＜0.001).TOMM40L levels were en-hanced in TNBC cell lines as compared to other non-TNBC cell lines.CCK-8 and Transwell assay demonstrated that TOMM40L knockdown reduced the proliferation and migration of TNBCcell lines.Functional enrichment analysis showed that TOMM40L was involved in glucose metabolism-related pathways.Conclusions The expression of TOMM40L is increased in TNBC and is correlated with poor prognosis.TOMM40L may promote TNBC migration and proliferation.

Objective:To explore the potential causal relationships between major depressive disorder(MDD),anxiety disorder(AD)and various highly prevalent cancers from the genetic perspective.Methods:Sum-mary statistics from large-scale genome-wide association studies(GW AS)were analyzed using a bidirectional two-sample Mendelian randomization(MR)approach.The inverse variance weighting method(IVW)was usedas the main analytical approach.The intercept term of MR-Egger regression and the MR-PRESSO method were adopted for the pleiotropy test.Results:The IVW analysis revealed potential causal relationships between MDD and breast cancer[OR(95％CI):1.11(1.01-1.22),P＜0.05],AD and lung cancer[OR(95％CI):1.30(1.02-1.65),P＜0.05],and between colon cancer and MDD[OR(95％CI):1.05(1.00-1.11),P＜0.05].The results of the pleiotropy test showed that the intercept terms of the MR-Egger regression were not statistically significant,indica-ting the absence of pleiotropy.The MR-PRESSO method detected outliers only in the relationship between MDD and breast cancer.The association between MDD and breast cancer remained significant after correction for outliers[OR(95％CI):1.10(1.03-1.17),P＜0.05].Conclusion:The study suggests that MDD may be a risk factor for breast cancer,AD may increase the risk factor for lung cancer,and colon cancer may elevate the risk factor of MDD.Moreover,the possibility of reverse causal relationships has been excluded in all these cases.

Transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR) is known as M-TEER. Its strengths include: precise targets and fewer implants; simple and clear principles for catheterization; originating from dependable medical concepts and broad applicability. Furthermore, TEER offers advantages in real-time hemodynamic and effectiveness measurement throughout the procedure over surgical edge-to-edge repair (SEER). When it comes to patients with degenerative mitral regurgitation , M-TEER should aim to deliver more optimum procedural outcomes. In functional mitral regurgitation, a modest transvalvular gradients or moderate residual shunt can be tolerated with M-TEER, which reduces the risk of problems and has no bearing on the patient's prognosis.

Objectives:To observe the mitochondrial morphology of normal and triple-negative breast cancer cells, extract mitochondria from normal cells, and investigate the effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of triple-negative breast cancer cells.Methods:The morphology of mitochondria was observed by transmission electron microscope. Mitochondria were extracted by mitochondrial extraction kit, mitochondrial protein was identified by western blot, and mitochondrial activity was detected by mitochondrial membrane potential detection kit. MitoTracker Green or MitoTracker Deep Red fluorescent probes were used to label the mitochondria of living cells, and the degree of mitochondria entering LTT cells was observed by confocal laser microscopy at 12, 24, and 96 hours. The effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of breast cancer cells were examined by CCK8, colony formation assay, flow cytometry, and sphere formation assay after 24 hours of mitochondrial transplantation.Results:The mitochondria of normal cells were rod-shaped or elongated, while the mitochondria of triple-negative breast cancer cells were swollen and vacuolated. Western blot results showed that cytochrome c oxidase subunit I (MT-CO1) protein encoded by mitochondria was present in the isolated mitochondria. The content of heat shock protein 60 (HSP60) was higher in mitochondria than that in cytoplasm. The result of the multi-mode microplate reader showed that the content of mitochondrial J-aggregates/monomer was 1.67±0.06, which was significantly higher than 0.35±0.04 of the control group ( P＜0.001). Exogenous mitochondria were observed in LTT cells at 12, 24, and 96 hours after mitochondrial transplantation. The results of the CCK8 experiment showed that OD450 of LTT cells was 0.27±0.13 after 48 hours transplantation, which was lower than 0.62±0.36 of the control group ( P=0.023). The OD450 of MDA-MB-468 cells was 0.30±0.03, which was lower than 0.65±0.10 of the control group ( P=0.004). After 120 hours of mitochondrial transplantation, OD450 in both groups was still significantly lower than that in the control group (P＜0.01). The number of clones formed by mitochondrial transplantation of LTT cells was 21.33±7.31, which was lower than 35.22±13.59 of the control group ( P=0.016). Flow cytometry showed that the early apoptosis rate of LTT cells was (30.07±2.15)% after 24 hours of mitochondrial transplantation, which was higher than 2.07±1.58 of the control group ( P＜0.001). The proportion of early apoptosis in MDA-MB-468 cells was 24.47%±5.22%, which was higher than (7.83±2.06)% in the control group ( P=0.007). In addition, the number of mitochondria transplanted LTT cells into the cell sphere was 46.25±5.40, which was significantly lower than 62.58±6.43 of the control group ( P＜0.001). Conclusion:Normal mitochondria can enter triple-negative breast cancer cells by co-culture, inhibit the proliferation and stemness of triple-negative breast cancer cells, and promote the apoptosis of triple-negative breast cancer cells.

Objectives:To observe the mitochondrial morphology of normal and triple-negative breast cancer cells, extract mitochondria from normal cells, and investigate the effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of triple-negative breast cancer cells.Methods:The morphology of mitochondria was observed by transmission electron microscope. Mitochondria were extracted by mitochondrial extraction kit, mitochondrial protein was identified by western blot, and mitochondrial activity was detected by mitochondrial membrane potential detection kit. MitoTracker Green or MitoTracker Deep Red fluorescent probes were used to label the mitochondria of living cells, and the degree of mitochondria entering LTT cells was observed by confocal laser microscopy at 12, 24, and 96 hours. The effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of breast cancer cells were examined by CCK8, colony formation assay, flow cytometry, and sphere formation assay after 24 hours of mitochondrial transplantation.Results:The mitochondria of normal cells were rod-shaped or elongated, while the mitochondria of triple-negative breast cancer cells were swollen and vacuolated. Western blot results showed that cytochrome c oxidase subunit I (MT-CO1) protein encoded by mitochondria was present in the isolated mitochondria. The content of heat shock protein 60 (HSP60) was higher in mitochondria than that in cytoplasm. The result of the multi-mode microplate reader showed that the content of mitochondrial J-aggregates/monomer was 1.67±0.06, which was significantly higher than 0.35±0.04 of the control group ( P＜0.001). Exogenous mitochondria were observed in LTT cells at 12, 24, and 96 hours after mitochondrial transplantation. The results of the CCK8 experiment showed that OD450 of LTT cells was 0.27±0.13 after 48 hours transplantation, which was lower than 0.62±0.36 of the control group ( P=0.023). The OD450 of MDA-MB-468 cells was 0.30±0.03, which was lower than 0.65±0.10 of the control group ( P=0.004). After 120 hours of mitochondrial transplantation, OD450 in both groups was still significantly lower than that in the control group (P＜0.01). The number of clones formed by mitochondrial transplantation of LTT cells was 21.33±7.31, which was lower than 35.22±13.59 of the control group ( P=0.016). Flow cytometry showed that the early apoptosis rate of LTT cells was (30.07±2.15)% after 24 hours of mitochondrial transplantation, which was higher than 2.07±1.58 of the control group ( P＜0.001). The proportion of early apoptosis in MDA-MB-468 cells was 24.47%±5.22%, which was higher than (7.83±2.06)% in the control group ( P=0.007). In addition, the number of mitochondria transplanted LTT cells into the cell sphere was 46.25±5.40, which was significantly lower than 62.58±6.43 of the control group ( P＜0.001). Conclusion:Normal mitochondria can enter triple-negative breast cancer cells by co-culture, inhibit the proliferation and stemness of triple-negative breast cancer cells, and promote the apoptosis of triple-negative breast cancer cells.

[摘 要] 目的：探索抗HSP90单克隆抗体28C10通过靶向肿瘤干细胞促进顺铂（cisplatin，DDP）对人胃癌细胞PAMC82恶性生物学行为的抑制效果及其可能的作用机制。方法: 28C10单独或与DDP联合处理人胃癌细胞PAMC82，采用不同实验方法检测该细胞的无血清成球能力、迁移和侵袭能力与克隆形成能力，CCK-8法检测28C10对PAMC82细胞恶性生物学行为和协同DDP抗癌能力的影响。采用细胞免疫荧光及流式细胞术检测PAMC82细胞中HSP90及eHSP90（extracellular HSP90）的表达、定位、eHSP90+亚群比例，以及28C10处理后对ALDH+、CD44+、eHSP90+细胞亚群的影响。采用WB实验检测28C10作用后PAMC82细胞中HSP90、干性相关蛋白以及PI3K/AKT/mTOR信号通路蛋白表达的变化。结果：胃癌细胞PAMC82膜表面表达eHSP90，具有2%~3%的eHSP90+细胞亚群，且eHSP90+细胞多为与ALDH+或CD44+共阳性细胞。28C10处理能显著抑制PAMC82细胞的成球、克隆形成、增殖、耐药、迁移及侵袭能力，而且和DDP联用的效果更明显（P<0.05或P<0.01）。流式细胞术分析发现28C10处理显著抑制PAMC82细胞的eHSP90+、ALDH+和CD44+亚群数量（均P<0.01）。免疫荧光实验发现28C10作用后eHSP90发生内吞，WB实验结果显示eHSP90、CD44、ALDH和干性相关蛋白OCT4、SOX2表达量均降低（P<0.05或P<0.01）。结论：抗HSP90单克隆抗体28C10可靶向胃癌PAMC82细胞的ALDH+、CD44+肿瘤干细胞相关亚群、内化eHSP90且降低细胞总HSP90的水平、抑制PI3K/AKT/mTOR信号通路，从而有效地抑制PAMC82细胞的干性、耐药和其他恶性生物学行为，协同DDP显著提高抗癌效果。

Mitral regurgitation is one of the most common heart valve diseases. Transcatheter edge-to-edge repair (TEER) is currently the most developed and commonly used interventional technique for mitral regurgitation and is recommended by the latest European and American guidelines for patients who are at high surgical risk. TEER device usually consists of a clamping device and a delivery system. The trajectory of the clamping device is called the trajectory, and the trajectory can be well established with the five dimensions movement of the delivery system: left-right oscillation, anterior-posterior oscillation, overall parallel movement, the clamping device's own clockwise rotation, and vertical up-and-down movement. The delivery system's anteroposterior and lateral oscillations are concentrated on the virtual puncture site. Furthermore, the location of the septal puncture site has a significant impact on the establishemnt of the trajectory. The evulation of three variables and adherence to the "4M principles" are necessary for the successful TEER. The three variables are: the position of the clip in the center of the regurgitation,the arm orientation of the clip perpendicular to the boundary of anterior and posterior leaflets, as well as the appropriate length of clamping. The "4M principles" include favorable valve morphology, residual mitral regurgitation below grade 2+, mean transvalvular pressure≤5 mm Hg, and an appropriate amount of leaflets clamping. Patients' baseline situation, the degree of mitral regurgitation and ventricular remodeling, as well as the valve morphology and the outcome of the procedure, are the factors determining the prognosis of patients after TEER.

Transcatheter edge-to-edge repair (TEER) originated from surgical edge-to-edge repair. MitraClip is the first mature TEER device, and the TEER based on MitraClip is far ahead of many transcatheter mitral valve repair (TMVr) technologies in terms of safety, effectiveness and popularity, so it is named separately in the latest guidelines. The TEER has the following advantages: consistent with basic medical principles, few implants, precise target, less invasive and repeatable. However, there are also some shortcomings, such as the relatively complex design of transfemoral device, target single and relatively narrow indications. At present, the main clinical data of TEER are mainly from the clinical practice of MitraClip. Based on the three-year outcomes of COAPT study, both 2020 ACC/AHA guideline and 2020 ACC expert consensus decision pathway on the management of mitral regurgitation recommend in patients with chronic heart failure with left ventricular dysfunction and severe mitral regurgitation in nonresponders to medicine treatment. Edward's PASCAL, another TEER device, has two models. Among the domestic TEER devices, the ValveClamp of Hanyu medical technology has many distinct advantages, such as simple operation, large clamping area, high clamping efficiency and no need of X-ray. DragonFly, another domestic TEER device, has also completed its feasibility study. There are five trends of TEER in the future: further expansion of indications, combination with other interventional techniques, repeatable operations, transcatheter mitral valve replacement after TEER, and continuous improvement and innovation of equipment.