OBJECTIVE: To observe the effect of Guilu Taohong Formula on semen quality in varicocele (VC) models of rats, and to explore its possible mechanism. METHODS: Forty-eight male SD rats were randomly divided into four groups (sham group, model group, Guilu Taohong Formula group and L-carnitine group). After the establishment of models, the rats were treated with intragastric administration for eight consecutive weeks. The general condition of the rats was observed. After the gavage, the testicular and epididymal indices were calculated. Semen quality was assessed using an automatic semen analyzer. Apoptosis of testicular cells was assessed by TUNEL staining. And the expression levels of B-cell lymphocytoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine aspartate protease-3 (caspase-3) in testicular tissue were detected by Western blot. RESULTS: Compared with the sham group, testicular index, epididymal index, sperm concentration, the percentage of progressive motility of sperm (PR%) and the expression level of Bcl-2 decreased in model group(P<0.01). An increased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were observed in model group as well(P<0.01). Compared with the model group, the testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 in Guilu Taohong Formula group increased significantly (P<0.05, P<0.01). A decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were detected in Guilu Taohong Formula group as well(P<0.01). Similarly, the L-carnitine group showed increased testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 protein (P<0.05, P<0.01), where showed decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins compared with model group (P<0.01, P<0.05). CONCLUSION Guilu Taohong Formula improves semen quality in VC model rats and reduces the apoptosis rate of spermatogenic cells in testicular tissue, which may be related to the promotion of Bcl-2 protein expression and the inhibition of Bax and caspase-3 protein expression levels.
Male ; Animals ; Varicocele/drug therapy* ; Rats ; Apoptosis/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Semen Analysis ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal ; Spermatozoa/drug effects* ; Testis/drug effects*

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

BACKGROUND:Glucocorticoids can inhibit the expression of hub genes in the parathyroid hormone type Ⅰ receptor(PTH1R)/protein kinase A(PKA)signaling axis and interfere with the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells,leading to the disruption of blood supply in bone and bone tissue structures.Previous studies of the research team showed that Gubitongxiao granules can induce blood vessel formation and inhibit osteoblast apoptosis,which has a certain effect on the prevention and treatment of steroid-induced femoral head necrosis. OBJECTIVE:To observe the therapeutic effect of Gubitongxiao granules in a mouse model of steroid-induced femoral head necrosis,and to explore its mechanism from the PTH1R/PKA signaling axis. METHODS:An animal model of steroid-induced necrosis of the femoral head was established by intraperitoneal injection of lipopolysaccharide and gluteal muscle injection of prednisolone acetate.After identification by nuclear magnetic resonance method,60 mice that were successfully modeled were divided into model group,Gubitongxiao granule group and Tongluo Shenggu capsule group,with 20 mice in each group.Another 12 normal mice were used as control group.The corresponding groups were intragastrically given the corresponding drugs for 12 weeks,and then the samples were taken under anesthesia.Histomorphology of femoral head samples was observed by hematoxylin-eosin staining.Enzyme-linked immunosorbent assay was used to detect the serum levels of bone alkaline phosphatase,type Ⅰ amino-terminal extension peptide,parathyroid hormone,osteocalcin and alkaline phosphatase.Western blot and RT-qPCR were used to detect PTH1R,PKA,myocyte enhancer factor 2,sclerostin and guanylate-binding protein activity-stimulating peptide at protein and gene expression levels,respectively. RESULTS AND CONCLUSION:Gubitongxiao granules may reduce the serum PTH level in mice,inhibit the activation of the PTH1R/PKA signal axis,further up-regulate the protein expressions of sclerostin and myocyte enhancer factor 2,and increase the levels of bone alkaline phosphatase,type Ⅰ amino-terminal extension peptide,osteocalcin and alkaline phosphatase in mice,thus improving femoral head necrosis,which is comparable to the intervention effect of Tongluo Shenggu capsules.It is speculated that Gubitongxiao granules may prevent and treating hormonal femoral head necrosis by regulating the PTH1R/PKA signaling axis.

Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.

Acute myocardial infraction(AMI)has now become a threat to human health worldwide.Therefore,it is urgent to construct the standardized platform of integrated traditional Chinese and western medicine diagnosis and treatment for AMI.The Intensive Care Unit(ICU)team of the Second Clinical Medical School of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine)has taken up the mission of exploring the prevention and treatment of AMI with traditional Chinese medicine and promoting and the construction of the diagnosis and treatment system of integrated traditional Chinese and western medicine for AMI.The team pioneered the trinity mode of'saving heart,treating heart and nourishing heart'for AMI,focusing on the construction of standardized platform of integrated traditional Chinese and western medicine diagnosis and treatment for AMI,creating the key technology system of Yiqi Huoxue Huatan method(the therapy mainly for replenishing qi,activating blood and dissolving phlegm)for AMI and putting it into the practice,which highlighted the achievements in the construction of the standardized platform.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Using machine learning algorithms to construct an early prediction model of brucellosis to improve the diagnosis efficiency of Brucellosis. This study was a case-control study. 2 381 brucellosis patients from Beijing Ditan Hospital affiliated to Capital Medical University were retrospectively collected as case group, and healthy people from Beijing Chaoyang Hospital affiliated to Capital Medical University were collected as control group from May 9, 2011 to November 29, 2021. The relevant clinical information and full blood count results of 13 257 data were collected and five algorithms of machine learning were used to construct an early predication model of brucellosis by using machine learning: random forest, Naive Bayes, decision tree, logistic regression and support vector machine;14 074 data (2 143 cases incase group and 11 931 cases in control group) were used to establish the early predication model of brucellosis, and 1 564 (238 cases in case group and 1 326 cases in control group) data were used to test the predication efficiency of the brucellosis model. The results showed that the support vector machine algorithm has the best predication performance by comparing the five machine learning models. The area under receiver curve (AUC) of receiver operating characteristic (ROC) was 0.991, and the accuracy, precision, specificity and Recall were 95.6%, 95.5%, 95.4% and 95.9%, respectively. Based on the SHAP plot, platelet distribution width (PDW) and basophil relative value (BASO%) results were low, and men with high coefficient of variation (R-CV), erythrocyte hemoglobin concentration (MCHC), and platelet volume (MPV) were predicted to be at high risk of brucellosis. Platelet distribution width (PDW) contributed the most to the prediction model, followed by red blood cell distribution width coefficient of variation (R-CV). In conclusion, the establishment of a high-precision early predication method of brucellosis based on machine learning may be of great significance for the early detection and treatment of brucellosis patients.
Male ; Humans ; Retrospective Studies ; Case-Control Studies ; Bayes Theorem ; Algorithms ; Machine Learning

Objectives: To evaluate the feasibility and preliminary clinical results of transcatheter pulmonary valve replacement (TPVR) with the domestically-produced balloon-expandable Prizvalve system. Methods: This is a prospective single-center observational study. Patients with postoperative right ventricular outflow tract (RVOT) dysfunction, who were admitted to West China Hospital of Sichuan University from September 2021 to March 2023 and deemed anatomically suitable for TPVR with balloon-expandable valve, were included. Clinical, imaging, procedural and follow-up data were analyzed. The immediate procedural results were evaluated by clinical implant success rate, which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitationResults: A total of 5 patients were included, with 4 males, aged 14 to 37 years. The initial diagnosis included Tetralogy of Fallot (2 cases), truncus arteriosus (1 case), pulmonary atresia (1 case) and subaortic stenosis (1 case, prior Ross procedure). Four patients underwent RVOT reconstruction with homograft or artificial conduit, and one patient was treated with trans-annular patch technique. The indications of TPVR included RVOT obstruction and regurgitation (3 cases), isolated obstruction (1 case), and isolated regurgitation (1 case). Of the 4 patients with varying severity of ROVT obstruction, the average preprocedural peak jet velocity of RVOT was 3.5 m/s, and the average peak pressure gradient was 50.0 mmHg. Except for one patient, who had previously been implanted with a covered Cheatham-Platinum (CP) stent due to severe stenosis of the main pulmonary artery, other patients underwent pre-stenting with a covered CP stent before TPVR. Clinical implant success was achieved in all of the 5 patients, and there was no serious periprocedural complications. The average trans-pulmonary peak jet velocity and peak pressure gradient derived from postprocedural echocardiography was 2.3 m/s and 21.2 mmHg, respectively. All patients experienced significant symptom relief after the procedure. All patients completed 3-month follow-up, and 4 completed 6-month follow-up. There was no case of infectious endocarditis during follow-up. All patients were graded as NYHA functional class one at the latest follow-up. Conclusions: TPVR using the domestically-produced balloon-expandable Prizvalve system is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable landing-zone anatomy. The safety, effectiveness, and long-term valve durability of the Prizvalve system deserve further research.
Male ; Humans ; Pulmonary Valve/surgery* ; Heart Valve Prosthesis/adverse effects* ; Heart Valve Prosthesis Implantation ; Constriction, Pathologic/surgery* ; Prospective Studies ; Ventricular Outflow Obstruction/surgery* ; Treatment Outcome ; Cardiac Catheterization/methods* ; Transcatheter Aortic Valve Replacement

Using machine learning algorithms to construct an early prediction model of brucellosis to improve the diagnosis efficiency of Brucellosis. This study was a case-control study. 2 381 brucellosis patients from Beijing Ditan Hospital affiliated to Capital Medical University were retrospectively collected as case group, and healthy people from Beijing Chaoyang Hospital affiliated to Capital Medical University were collected as control group from May 9, 2011 to November 29, 2021. The relevant clinical information and full blood count results of 13 257 data were collected and five algorithms of machine learning were used to construct an early predication model of brucellosis by using machine learning: random forest, Naive Bayes, decision tree, logistic regression and support vector machine;14 074 data (2 143 cases incase group and 11 931 cases in control group) were used to establish the early predication model of brucellosis, and 1 564 (238 cases in case group and 1 326 cases in control group) data were used to test the predication efficiency of the brucellosis model. The results showed that the support vector machine algorithm has the best predication performance by comparing the five machine learning models. The area under receiver curve (AUC) of receiver operating characteristic (ROC) was 0.991, and the accuracy, precision, specificity and Recall were 95.6%, 95.5%, 95.4% and 95.9%, respectively. Based on the SHAP plot, platelet distribution width (PDW) and basophil relative value (BASO%) results were low, and men with high coefficient of variation (R-CV), erythrocyte hemoglobin concentration (MCHC), and platelet volume (MPV) were predicted to be at high risk of brucellosis. Platelet distribution width (PDW) contributed the most to the prediction model, followed by red blood cell distribution width coefficient of variation (R-CV). In conclusion, the establishment of a high-precision early predication method of brucellosis based on machine learning may be of great significance for the early detection and treatment of brucellosis patients.
Male ; Humans ; Retrospective Studies ; Case-Control Studies ; Bayes Theorem ; Algorithms ; Machine Learning

Objective:To evaluate the efficacy and safety of immediate intraoperative transapical beating-heart septal myectomy (TA-BSM) in patients with hypertrophic obstructive cardiomyopathy (HOCM) and explored the clinical value of three-dimensional transesophageal echocardiography (3D-TEE) during the procedure of TA-BSM.Methods:One hundred and thirty-seven HOCM patients who underwent TA-BSM surgery in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from April 2022 to March 2023 were selected.During the operation, 3D-TEE was used to locate the position of the myocardial circumcision system and navigate the range of myocardial circumcision. The interventricular septal thickness( IVST) and peak pressure gradient of the left ventricular outflow tract (LVOT-PG) were measured, and the degree of mitral systolic anterior motion (SAM) and mitral regurgitation (MR) were evaluated in HOCM patients before and after the operation. The range of the incisal margin was measured, and the number of resection knives and the weight of the removed myocardium were recorded.Results:TA-BSM under 3D-TEE navigation was successfully performed in 137 HOCM patients. The number of resection was 7(5, 9), and the weight of the removed myocardium was 5.6(3.4, 8.9)g. During the operation, there were no adverse events such as death, aortic valve injury, and iatrogenic interventricular septal perforation. Compared with those before the operation, the wall thickness of basal and middle segments of the anterior and posterior interventricular septum decreased significantly (all P<0.001), and LVOT-PG decreased significantly ( P<0.001). After TA-BSM, the number of patients with SAM≥3 decreased from 94 cases (68.6%) to 2 cases (1.5%), and the number of patients with MR≥3+ decreased from 86 cases (62.8%) to 9 cases (6.6%)(all P<0.001). For the patients with different degrees of ventricular septal hypertrophy (mild, moderate, and severe), the postoperative IVST and LVOT-PG were significantly lower than the preoperative values, and the degree of MR and SAM signs was relieved considerably. The length of the incisal margin, the weight of excised myocardium, and the number of resection in the group with extensive septal hypertrophy in all three regions were significantly higher than those in the group with localized interventricular septal hypertrophy in single or two areas (all P<0.05). Conclusions:3D-TEE can guide and monitor the process of TA-BSM myocardial resection in real-time. By accurately evaluating the IVST and the range and hemodynamic characteristics of HOCM patients, it can effectively relieve LVOTO and significantly reduce MR to ensure the safety and effectiveness of TA-BSM in HOCM patients with different degrees and ranges of hypertrophy.