Objective To compare the mid- and long-term clinical results of mitral valve plasty (MVP) and mitral valve replacement (MVR) in the treatment of functional mitral regurgitation (FMR). Methods Patients with FMR who underwent surgical treatment in the Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command from 2012 to 2021 were collected. The patients who underwent MVP were divided into a MVP group, and those who underwent MVR into a MVR group. The clinical data and mid-term follow-up efficacy of two groups were compared. Results Finally 236 patients were included. There were 100 patients in the MVP group, including 53 males and 47 females, with an average age of (61.80±8.03) years. There were 136 patients in the MVR group, including 72 males and 64 females, with an average age of (61.29±8.97) years. There was no statistical difference in baseline data between the two groups (P＞0.05). There was no statistical difference between the two groups in the extracorporeal circulation time, aortic occlusion time, postoperative hospital and ICU stay, intraoperative blood loss, or hospitalization death (P＞0.05), but the time of mechanical ventilation in the MVP group was significantly shorter than that in the MVR group (P=0.022). The total follow-up rate was 100.0%, the longest follow-up was 10 years, and the average follow-up time was (3.60±2.55) years. There were statistical differences in the left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac function between the two groups compared with those before surgery (P<0.05). The postoperative left ventricular ejection fraction in the MVP group was statistically higher than that before surgery (P=0.002), but there was no statistical difference in the MVR group before and after surgery (P=0.658). The left atrial diameter in the MVP group was reduced compared with the MVR group (P=0.026). The recurrence rate of mitral regurgitation in the MVP group was higher than that in the MVR group, and the difference was statistically significant (10.0% vs. 1.5%, P=0.003). There were 14 deaths in the MVP group and 19 in the MVR group. The cumulative survival rate (P=0.605) and cardiovascular events-free survival rate (P=0.875) were not statistically significant between the two groups by Kaplan-Meier survival analysis. Conclusion The safety, and mid- and long-term clinical efficacy of MVP in the treatment of FMR patients are better than MVR, and the left atrial and left ventricular diameters are statistically reduced, and cardiac function is statistically improved. However, the surgeon needs to be well aware of the indications for the MVP procedure to reduce the rate of mitral regurgitation recurrence.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

A 72-year-old patient with quadricuspid aortic valve underwent transcatheter aortic valve replacement due to severe valve stenosis accompanied by moderate insufficiency. As initially planned, the right coronary artery was protected during the procedure. However, after the artificial valve was released, the left coronary artery was found to be blocked, so a coronary protection stent was implanted in the left coronary artery ostium under the guidance of intravascular ultrasonography. This case indicates that for patients with a quadricuspid aortic valve undergoing transcatheter aortic valve replacement, in addition to preoperative measurement of the aortic root, attention should also be paid to the coronary artery obstruction caused by the displacement of the artificial valve frame during the procedure.
Aged ; Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Coronary Vessels ; Stents ; Transcatheter Aortic Valve Replacement/methods*

Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.
Humans ; Neoplasms/metabolism* ; Cyclin-Dependent Kinases/antagonists & inhibitors* ; Cyclins/metabolism* ; Proteolysis ; Antineoplastic Agents/pharmacology* ; Molecular Targeted Therapy ; Proteasome Endopeptidase Complex/metabolism* ; Animals

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

Objective To investigate the safety and efficacy of mitral valve replacement combined with cryoablation Maze surgery in patients with atrial functional mitral regurgitation (AFMR). Methods From January 2014 to June 2020, patients with AFMR who underwent mitral valve replacement in our department were enrolled. They were divided into two groups, a cryoablation Maze group who received cryoablation Maze surgery during mitral valve replacement, and a non-cryoablation Maze group who did not receive cryoablation Maze surgery. The baseline data, surgical data, efficacy, and prognosis between the two groups were compared. Results Finally 85 patients were enrolled. There were 16 males and 24 females with an average age of 58.65±6.86 years in the cryoablation Maze group, and 24 males and 21 females with an average age of 61.29±8.30 years in the non-cryoablation Maze group. There was no statistical difference in baseline data between the two groups (P＞0.05). The aortic occlusion time and extracorporeal circulation time of the cryoablation Maze group were longer than those of the non-cryoablation Maze group with statistical differences (P＜0.01). There was no statistical difference in postoperative ICU retention time, ventilator assistance time, length of hospital stay, intraoperative blood loss, drainage volume on the first day or occurrence rate of complications (temporary pacemaker application, electrical cardioversion, thoracic puncture drainage, hospitalization death) between the two groups (P＞0.05). At the time of discharge, postoperative 3-month, 6-month, 12-month, and 24-month, the maintenance rates of sinus rhythm in the non-cryoablation Maze group were statistically different from those of the cryoablation Maze group (P＜0.001). Compared with the non-cryoablation Maze group, the decrease values of left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and pulmonary artery systolic pressure were statistically different (P＜0.05). Postoperative cardiac function grading of both groups was grade Ⅰ or Ⅱ, which was significantly improved compared with preoperative level, but there was no statistical significance between the two groups (P＞0.05). There was no statistical difference in the incidence of adverse events during follow-up (P＞0.05). Conclusion Cryoablation Maze surgery combined with mitral valve replacement is safe and effective in the treatment of AFMR patients, which is conducive to the recovery and maintenance of sinus rhythm, and is beneficial to the remodeling of the left atrium and left ventricle, the reduction of pulmonary systolic blood pressure, and the improvement of life quality of the patients.

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

Objective To evaluate the incidence of postoperative atrial fibrillation (POAF) after dexmedetomidine and diazepam in patients undergoing coronary artery bypass grafting (CABG). Methods A retrospective cohort study was conducted in the patients who underwent CABG in the General Hospital of Northern Theater Command from October 2020 to June 2021. By propensity score-matching method, the incidence of POAF after dexmedetomidine and diazepam application in patients undergoing CABG was evaluated. Results Finally 207 patients were collected, including 150 males and 57 females, with an average age of 62.02±8.38 years. Among the 207 patients, 53 were treated with dexmedetomidine and 154 with diazepam before operation. There was a statistical difference in the proportion of hypertension patients and smoking patients between the two groups before matching (P<0.05). According to the 1∶1 propensity score-matching method, there were 53 patients in each of the two groups, with no statistical difference between the two groups after matching. After matching, the incidence of POAF in the dexmedetomidine group was lower than that in the diazepam group [9.43% (5/53) vs. 30.19% (16/53), P=0.007]. There was no death in the two groups during hospitalization, and there was no statistical difference in the main adverse events after operation. The ICU stay (21.28±2.69 h vs. 22.80±2.56 h, P=0.004) and mechanical ventilation time (18.53±2.25 h vs. 19.85±2.01 h, P=0.002) in the dexmedetomidine group were shorter. Regression analysis showed that age, smoking and diabetes were related to the increased incidence of POAF (P<0.05), and preoperative use of dexmedetomidine was associated with a reduced incidence of POAF (P=0.002). Conclusion For patients undergoing CABG, the incidence of POAF with dexmedetomidine before operation is lower than that with diazepam. Preoperative application of dexmedetomidine is the protective factor for POAF, and old age, smoking and diabetes are the risk factors for POAF.

To fulfill the calibration requirements for absorbed dose to water in external beam radiotherapy,the summary offers a streamlined calibration procedure and recommendations in accordance with TRS-398(version 7)published by International Atomic Energy Agency in 2024.It addresses various considerations for reference measurement conditions in external beam radiotherapy and defines the appropriate scope for ionization chambers.In terms of ionization chamber measurements,it elaborates on the methods for measuring various correction factors and provides a table of beam quality conversion factors.The calibration uncertainty is examined by comparing the contributions of different factors before and after the update.The results demonstrate that using IBA FC65-G ionization chamber to calibrate high-energy photon beams,high-energy electron beams,proton beams and light ion beams results in relative deviations of-0.4％,0.5％,-1.7％and-1.3％as compared with the earlier versions,with relative standard uncertainties of 1.0％,1.1％,1.7％and 2.6％,respectively.The guideline which is tailored to the national radiotherapy dose calibration standards and practices presents an optimized calibration approach for TRS-398,allowing clinicians to conduct absolute dose calibration more efficiently and accurately.

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.