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 analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.

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

Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis

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 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.

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27％),74 patients with BD-Ⅱ(19.42％)and 5 patients with other specific and related disorders(1.31％).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95％CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95％CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95％CI:1.76-75.30),and had lower education level(OR=10.22,95％CI:1.16-89.77),and less family history of psychosis(OR=2.34,95％CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.

Objective To analyze the safety and efficacy of neuroendoscopic minimally invasive surgery and traditional extraventricular drainage in the treatment of severe hypertensive intraventricular hemorrhage.Methods The clinical data of 50 cases with neuroendoscopic ventricular hematoma evacuation(endoscopy group)and 44 cases with traditional ventricles external puncture drainage(drainage group)from July 2020 to July 2023 were retrospectively analyzed,and the hematoma clearance rates,classification of activities of daily living(ADL)scale,incidence of hydrocephalus,secondary bleeding,intracranial infection,and pulmonary infection were observed between the two groups of patients.Results After surgery,the proportion of patients with hematoma clearance rate>60％and ADL grades Ⅰ,Ⅱ,and Ⅲ in the endoscopy group were significantly higher than those in the drainage group[the proportion of patients with hematoma clearance rate>60％:88.0％(44/50)vs.47.7％(21/44),χ2=17.794,P<0.001;the proportion of individuals with ADL grades Ⅰ,Ⅱ,and Ⅲ:94.0％(47/50)vs.77.3％(33/44),respectively,χ2=5.459,P=0.019],the incidence of complications in endoscopy group was significantly lower in the drainage group[8.0％(4/50)vs.34.1％(15/44),χ2=9.879,P=0.002].Conclusion Compared with traditional ventricular puncture drainage surgery,neuroendoscopic minimally invasive surgery for the treatment of severe hypertensive intracerebral hemorrhage with ventricular casting can achieve better treatment outcomes,a higher hematoma clearance rate,and fewer postoperative complications.

Objective To evaluate the efficacy of Jianpi Yang'er Ointment for children with anorexia of spleen deficiency type in Lingnan area;To analyze its effects on children's intestinal flora and functional information by means of metagenome sequencing.Methods Totolly 144 children with anorexia in Guangzhou Women and Children Medical Center of Guangzhou Medical University from August 2022 to January 2023 were orally treated with Jianpi Yang'er Ointment,one bag per time,twice a day,after meal,for 28 d.Visits were conducted at 0 and 28 days,respectively,to measure height and body mass,record symptoms and signs,observe adverse reactions,collect feces,and fill out the"Clinical Index Scoring Table for Children with Spleen Deficiency Type Anorexia in Lingnan Area".Clinically cured children were included in the anorexia group,with healthy children as a healthy control group(HC group),perform metagenomic analysis on feces of HC group and anorexia group 0 and 28 days of treatment.Results Compared with 0 d of treatment,there was no significant difference in the height of children(P>0.05),while there was a significant difference in body mass(P<0.05),the total syndrome score,main symptom score,and secondary symptom score decreased at 28 d of treatment(P<0.05).The efficacy index was 57.03%,and the total effective rate was 99.31%(143/144).All patients did not experience symptoms such as allergies,vomiting,or diarrhea.7 clinically cured children and 6 healthy children were included in metagenome analysis on feces.PCoA showed that the structure of intestinal flora in anorexia group with 28 d treatment(JP2 group)was more similar to that in HC group at the phylum and genus levels;at the phylum level,there was no significant difference in the distribution of intestinal flora between anorexia group with 0 d treatment(JP1)group and JP2 group and HC group.At the genus level,compared with JP1 group,the abundance of Bacteroides in JP2 group decreased,but the difference was not statistically significant(P>0.05);at the species level,both JP1 and JP2 groups were mainly composed of Phocaeicola plebeius et al.and Bifidobacterium pseudocatenatum et al.The biomarker with significant differences between the two groups was s_Phascolarctobacterium_faecium,while the HC group was mainly composed of Prevotella copri and Bifidobacterium pseudocatenatum.The functional annotation results indicated that a significant change in microbial functional genes related to carbohydrate metabolism occurred after the treatment with Jianpi Yang'er Ointment.Conclusion Jianpi Yang'er Ointment can effectively improve the clinical symptoms of children with spleen deficiency anorexia in Lingnan area,adjust the structure of intestinal flora,increase the content of key probiotics,and regulate the production of intestinal microbiota short-chain fatty acids.

OBJECTIVE To optimize the water extraction process of Flos Lonicerae-Fructus Forsythuae and determine the range of water extraction process parameters.METHODS The active components were screened by network pharmacology,and the indica-tor ingredients were determined in combination with the quality markers under the relevant terms of Chinese Pharmacopoeia 2020 edition and the literature.Take extraction yield and the extraction rate of the indicative component as the critical quality attributes of the water extraction process to screen critical process parameters.The mathematical model was established by Box-Behnken experimental design to investigate the interaction between CQAs and CPPs and build the design space of the water extraction process of Flos Lonicerae-Fruc-tus Forsythuae.RESULTS The extraction percentages of phenolic acids,forsythoside A and forsythin were screened as the index components;specifications of medicinal slices,extraction time and water addition were the key process parameters.Based on the estab-lishment and optimization of the design space,the optimum water extraction process was obtained as follows:the medicinal slice of Lian-Qiao was broken into 0.8-1.2 cm,adding 12 times the amount of water in the first and extract for 30-50 min,10 times the a-mount of water in the second and extract for 25-30 min.CONCLUSION The verification results show that the measured value ob-tained by using the design space method to optimize the water extraction process is close to the predicted value,indicating that the method is stable and reliable,which can provide ideas for its further process development and quality control for the couple medicines of Flos Lonicerae-Fructus Forsythuae.