Objective To examine the safety, efficacy and durability of totally endoscopic minimally invasive (TEMI) mitral valve repair in Barlow’s disease (BD). Methods A retrospective study was performed on patients who underwent mitral valve repair for BD from January 2010 to June 2021 in the Guangdong Provincial People’s Hospital. The patients were divided into a MS group and a TEMI group according to the surgery approaches. A comparison of the clinical data between the two groups was conducted. Results A total of 196 patients were enrolled, including 133 males and 63 females aged (43.8±14.9) years. There were 103 patients in the MS group and 93 patients in the TEMI group. No hospital death was observed. There was a higher percentage of artificial chordae implantation in the TEMI group compared to the MS group (P=0.020), but there was no statistical difference between the two groups in the other repair techniques (P>0.05). Although the total operation time between the two groups was not statistically different (P=0.265), the TEMI group had longer cardiopulmonary bypass time (P<0.001) and aortic clamp time (P<0.001), and shorter mechanical ventilation time (P<0.001) and postoperative hospitalization time (P<0.001). No statistical difference between the two groups in the adverse perioperative complications (P>0.05). The follow-up rate was 94.2% (180/191) with a mean time of 0.2-12.4 (4.0±2.4) years. Two patients in the MS group died with non-cardiac reasons during the follow-up period. The 3-year, 5-year and 10-year overall survival rates of all patients were 100.0%, 99.2%, 99.2%, respectively. Compared with the MS group, there was no statistical difference in the survival rate, recurrence rate of mitral regurgitation, reoperation rate of mitral valve or adverse cardiovascular and cerebrovascular events in the TEMI group (P＞0.05). Conclusion TEMI approach is a safe, feasible and effective approach for BD with a satisfying long-term efficacy.

Objective To assess the current status of occupational radiation hazards in animal diagnosis and treatment institutions in Foshan City. Methods A total of 214 animal diagnosis and treatment institutions in Foshan City in 2024 were selected as the study subjects using the judgment sampling method. The radiation protection management status was investigated. Results A total of 178 out of the 214 animal diagnosis and treatment institutions were equipped with radiation diagnostic equipment in Foshan City. Among these 178 institutions, 98 (accounting for 55.1%) obtained permits from the ecology and environmental department, 21 (accounting for 11.8%) completed occupational hazard project declarations, 53 (accounting for 29.8%) conducted workplace radiation level monitoring, 132 (accounting for 74.2%) were equipped with radiation protection equipment, 40 (accounting for 22.5%) conducted occupational health examinations for the radiation staff, 39 (accounting for 21.9%) provided radiation protection knowledge training for the radiation staff, and 52 (accounting for 29.2%) performed personal radiation dose monitoring. However, none of the institutions implemented the “Three Simultaneities (design, construct, put into operation and use simultaneously with the main body of the construction project)” system for occupational disease prevention facilities in construction projects. Conclusion sAnimal diagnostic and treatment institutions in Foshan City have low levels of radiation protection management and inadequate occupational health monitoring. The radiation staff has low awareness of radiation protection, Relevant department should strengthen supervision and management, organize radiation protection knowledge training, and standardize occupational health management to effectively safeguard workers' health rights.

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

Objective To develop a novel transcatheter tricuspid valve replacement device and test its performance. Methods The transcatheter tricuspid valve stent consisted of double-layer self-expanding nitinol stent, biotissue-derived bovine pericardial leaflets, and PTFE woven. The delivery system, mainly consisting of a handle control unit and a delivery sheath, was sent to the correct position via right atrium or jugular vein. The sheath had a visualization feature, and the handle control unit could realize the functions of stable release and partial recovery of the interventional valve. In addition, this study performed animal survival experiments on the basis of in vitro experiments. A large-white pig was used as the experimental animal. Cardiopulmonary bypass was established through median thoracotomy, then the right atrium was opened, and the interventional valve was released under direct vision without cardiac arrest. Approximately 1 month after interventional valve implantation, the maneuverability and stability of the interventional tricuspid device were evaluated by autopsy. Results Through the animal experiment, the interventional valve was successfully released, and the anchoring was satisfactory. Postoperative transthoracic echocardiography showed that the interventional valve opened and closed well, the flow rate of tricuspid valve was 0.6 m/s, and there was no obvious tricuspid regurgitation. One month after the operation, we dissected the large-white pig and found the interventional valve was not deformed or displaced, the leaflets were well aligned, and there was thrombus attachment in the groove between the inner and outer layers of the interventional valve. Conclusion Animal experiment shows that the novel device can stably and firmly attach to the tricuspid annulus, with good anchoring effect, and effectively reduce paravalvular leakage.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Objective To research the procedure for creating an animal model of mitral regurgitation by implanting a device through the apical artificial chordae tendineae, and to assess the stability and dependability of the device. Methods Twelve large white swines were employed in the experiments. Through a tiny hole in the apex of the heart, the artificial chordae tendineae of the mitral valve was inserted under the guidance of transcardiac ultrasonography. Before, immediately after, and one and three months after surgery, cardiac ultrasonography signs were noted. Results All models were successfully established. During the operation and the follow-up, no swines died. Immediately after surgery, the mitral valve experienced moderate regurgitation. Compared with preoperation, there was a variable increase in the amount of regurgitation and the values of heart diameters at a 3-month follow-up (P<0.05). Conclusion In off-pump, the technique of pulling the mitral valve leaflets with chordae tendineae implanted transapically under ultrasound guidance can stably and consistently create an animal model of mitral regurgitation.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective: To explore the activity of auranofin against ovarian cancer cells and its possible molecular mechanism． Methods : The dose-response survival curve and IC50 of auranofin on ovarian cancer cell lines ，SKOV3，Caov3 and SW626 cells and immortalized normal human embryonic kidney HEK-293T cells were determined by CCK-8 method．Cell cycle was determined by flow cytometry．The levels of total glutathione ( GSH) ，reduced GSH and glutathione disulfide ( GSSG) ，thioredoxin reductase (TrxR) and reactive oxygen species (ROS) in cells were determined by microplate reader，and the reduced GSH / GSSG ratio was calculated．Western blot was used to determine the expression of cyclin dependent kinases( CDK) 4，CDK6，Cyclin D1，P53，p-P53 and MDM2 in SKOV3 and Caov3 ovarian cancer cells. Results : Compared with HEK-293T cells，the dose-response survival curves and IC50 values of SKOV3，Caov3 and SW626 cells showed that ovarian cancer cells were more sensitive to auranofin (P＜0. 05) ．After SKOV3 and Caov3 cells were treated with the dose of respective IC50 concentrations of auranofin，compared with the untreated cells group，the Auranofin IC50 group cells' intracellular levels of GSH，the ratio of reduced GSH / GSSG and the activity of TrxR decreased (t = 25. 11 /31. 18，14. 72 /19. 92，43. 30 /10. 74， all P＜0. 05) ，and the levels of ROS increased (t = 23. 82 /27. 71，P＜0. 05) ; cells number at G0 / G1 phases increased，with cells number at S and G2 phases decreased (P＜0. 05) ; and the expression levels of cell cycle-related proteins CDK4，CDK6，Cyclin D1 and the P53-specific E3 ubiquitin ligase MDM2 were down-regulated (t = 7. 51 /15. 59，17. 32 /11. 26，20. 78 /20. 78，24. 25 /17. 32，all P＜0. 05) ，while the expression levels of P53 and p-P53 were up-regulated (t = 17. 32 /24. 25，12. 12 /10. 39，all P ＜0. 05) ． Conclusion Auranofin causes oxidative stress in ovarian cancer cells by inhibiting TrxR activity，and by partially degrading MDM2 to stabilize and acti- vate P53，so as to block the cancer cells in G0 / G1 phase，and exert anti-ovarian cancer activities.

The prevalence and mortality of cancer have been on the rise， and it has been the global leading cause of death. The causes of cancer are diverse， such as heredity， radiation， and carcinogens. The abnormality of cell cycle regulation is also one of the causes. Cell cycle is a complex sequence of events through which a cell duplicates its contents and divides. Cell cycle is highly organized to ensure the integrity of genetic material. This process involves many regulatory genes and proteins. Cell cycle will be dysregulated when these proteins and genes change， resulting in the loss of control of cell proliferation， the inhibition of apoptosis， and finally the occurrence of tumor. At the moment， the therapies for cancer include traditional surgical resection， radiotherapy， chemical therapy， and targeted therapy. Chinese medicine has a wide range of sources and little side effect， which is worthy of further research and development. More and more studies have revealed that a variety of Chinese medicines play an anti-tumor role by inducing cell cycle arrest， so as to improve the quality of life and prolong the survival time of patients with advanced tumors. This article first introduces the characteristics and related regulatory factors of each phase of cell cycle， and enumerates the clinical and experimental examples of tumorigenesis caused by abnormal cell cycle. Then， we summarize the hot anti-tumor drugs targeting cell cycle in China and abroad， such as Cyclin-dependent kinase （CDK） inhibitors， cell division cycle 25 （CDC25） inhibitors， ataxia-telangiectasia-mutated-and-Rad3-related kinase （ATR） inhibitors， and checkpoint kinase 1 （CHK1） inhibitors. Finally， this article summarizes the recent research on the anti-tumor effect of Chinese medicine by inducing cell cycle arrest from the three aspects of cell cycle G₀/G₁ phase， S phase and G₂/M phase， in order to provide some reference for the research on the anti-tumor effect of Chinese medicine.

Thoracoscopic minimally invasive technology has been used in mitral valve plasty since 1990s. Totally thoracoscopic mitral valve plasty has the advantages of small trauma, beautiful incision and rapid postoperative recovery. It is favored by more and more patients and cardiac surgeons. However, according to the reports, the proportion of totally thoracoscopic mitral valve surgery in China is still low. Mitral valve plasty via the totally thoracoscopic approach is still controversial in terms of population adaptation, perioperative complications and long-term prognosis. In addition, the technical difficulty and the long training cycle of surgeons also limit the popularization of this technology. By summarizing the existing literature, this paper analyzes the application and development of totally thoracoscopic approach in comparison with the traditional median thoracotomy mitral valve plasty.