Objective: To investigate the effect of intraarticular hemorrhage on extending knee joint contracture model in rats . Methods: 18 mature male SD rats were divided into 3 groups by random number table method . The control group ( group C) was not immobilized and was killed after 4 weeks of feeding . In the simple fixation group( M1 group) , the left lower limb knee joint was immobilized in straight position for 4 weeks . The blood fixationgroup (M2 group) was injected into the knee cavity with body blood and immobilized in a straight position for 4 weeks . The knee joint motion of each group was measured by the joint motion measuring instrument under a stand⁃ard torque . The contracture degree was calculated by the joint range of motion of the knee joint before and after muscles separation . HE staining and Masson staining were used to detect the number of cells and collagen deposi⁃tion in the anterior joint capsule . The protein expressions of transforming growth factor 1 (TGF⁃ β1) , wingless⁃type MMTV integration site family , member 1 ( Wnt1) and beta⁃catenin ( β⁃catenin) in the anterior articular capsule were detected by Western blotting . Results: Compared with group C , total knee contracture and arthrogenic con⁃tracture of rats in M1 and M2 groups increased , and the difference was statistically significant (P < 0. 05) . At the same time , the degree of total contracture and arthrogenic contracture in M2 group was higher than that in M1 group , and the difference was statistically significant (P < 0. 05) . Compared with group C , the number of anterior joint capsule cells and collagen deposition in M1 and M2 groups increased , and the difference was statistically sig⁃group were higher than those in M1 group , and the difference was statistically significant (P < 0. 05) . Compared with group C , the protein expressions of TGF⁃ β1 , Wnt1 and β ⁃catenin in the anterior articular capsule of rats in M1 expressions of TGF⁃ β1 , Wnt1 and β ⁃catenin in the anterior articular capsule of the knee joint in M2 group were sig⁃nificantly higher than those in M1 group , with statistical significance (P < 0. 05) . Conclusion Joint immobiliza⁃ tion can lead to joint contracture , and joint bleeding aggravates the degree of joint capsule fibrosis induced by im⁃mobilization .

Natural product-based drug combinations (NPDCs) present distinctive advantages in treating complex diseases. While high-throughput screening (HTS) and conventional computational methods have partially accelerated synergistic drug combination discovery, their applications remain constrained by experimental data fragmentation, high costs, and extensive combinatorial space. Recent developments in artificial intelligence (AI), encompassing traditional machine learning and deep learning algorithms, have been extensively applied in NPDC identification. Through the integration of multi-source heterogeneous data and autonomous feature extraction, prediction accuracy has markedly improved, offering a robust technical approach for novel NPDC discovery. This review comprehensively examines recent advances in AI-driven NPDC prediction, presents relevant data resources and algorithmic frameworks, and evaluates current limitations and future prospects. AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
Artificial Intelligence ; Biological Products/chemistry* ; Humans ; Drug Combinations ; Drug Discovery/methods* ; Machine Learning ; Algorithms

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

OBJECTIVES: To investigate the incidence of ipsilateral upper urinary tract stones after partial nephrectomy and its risk factors. METHODS: We retrospectively analyzed baseline patient characteristics (age, gender, and body mass index), smoking, alcohol consumption, comorbidities (hypertension, diabetes, hypertriglyceridemia, hyperuricemia, and cardiovascular diseases), preoperative tumor conditions (tumor diameter, multiple foci, location, hemorrhage, necrosis, cystic changes, and endophytic growth), preoperative glomerular filtration rate and intraoperative factors (renal collecting system damage, ischemia time, operation time, surgical approach, and estimated intraoperative blood loss) to identify the risk factors for ipsilateral upper urinary tract stones following partial nephrectomy in our center. RESULTS: The overall incidence of upper urinary tract stones following partial nephrectomy was 7.80% (112/1435). The incidence of ipsilateral upper urinary tract stones was significantly higher than those of contralateral stones (4.95% vs 1.46%, P<0.001) and bilateral stones (4.95% vs 1.39%, P<0.001). Intraoperative damage to the renal collecting system was identified as a significant risk factor for ipsilateral upper urinary tract stones (OR=4.550, 95% CI: 2.237-9.252, P<0.001). Diabetes was a probable risk factor for secondary ipsilateral upper urinary tract stones after partial nephrectomy (OR=2.419, 95% CI: 0.973-6.012, P=0.057). CONCLUSIONS The incidence of ipsilateral upper urinary tract stones after partial nephrectomy is higher than that of contralateral and bilateral stones. Intraoperative renal collecting system damage is a risk factor for secondary ipsilateral upper urinary tract stones after partial nephrectomy.
Humans ; Nephrectomy/methods* ; Retrospective Studies ; Risk Factors ; Male ; Female ; Case-Control Studies ; Middle Aged ; Aged ; Kidney Neoplasms/surgery* ; Adult ; Intraoperative Complications ; Kidney Tubules, Collecting/injuries* ; Propensity Score ; Incidence ; Kidney Calculi/etiology* ; Urinary Calculi/epidemiology*

The international dissemination of Chinese acupuncture represents a successful model of medical and cultural exchange between the East and the West, as well as an exemplary case of Chinese culture going global. In 1971, following the announcement by Xinhua News Agency that "acupuncture anesthesia technology had achieved success", American medical educator Professor Edmunds Grey Dimond became the first foreign doctor to visit China for an investigation of acupuncture anesthesia. His efforts significantly contributed to the promotion of Chinese acupuncture within western medical communities. From the perspective of acupuncture humanities, this article reviews and analyzes Dimond's academic background, his journey to study acupuncture anesthesia in China, and his unique insights into acupuncture, exploring how his open-minded and objective approach facilitated the acceptance and dissemination of acupuncture anesthesia and acupuncture techniques in the West.
China ; Humans ; History, 20th Century ; Acupuncture Therapy/history* ; Acupuncture/history* ; Acupuncture Analgesia/history* ; History, 21st Century

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

Objective To investigate the incidence of ipsilateral upper urinary tract stones after partial nephrectomy and its risk factors.Methods We retrospectively analyzed baseline patient characteristics(age,gender,and body mass index),smoking,alcohol consumption,comorbidities(hypertension,diabetes,hypertriglyceridemia,hyperuricemia,and cardiovascular diseases),preoperative tumor conditions(tumor diameter,multiple foci,location,hemorrhage,necrosis,cystic changes,and endophytic growth),preoperative glomerular filtration rate and intraoperative factors(renal collecting system damage,ischemia time,operation time,surgical approach,and estimated intraoperative blood loss)to identify the risk factors for ipsilateral upper urinary tract stones following partial nephrectomy in our center.Results The overall incidence of upper urinary tract stones following partial nephrectomy was 7.80%(112/1435).The incidence of ipsilateral upper urinary tract stones was significantly higher than those of contralateral stones(4.95%vs 1.46%,P<0.001)and bilateral stones(4.95%vs 1.39%,P<0.001).Intraoperative damage to the renal collecting system was identified as a significant risk factor for ipsilateral upper urinary tract stones(OR=4.550,95%CI:2.237-9.252,P<0.001).Diabetes was a probable risk factor for secondary ipsilateral upper urinary tract stones after partial nephrectomy(OR=2.419,95%CI:0.973-6.012,P=0.057).Conclusions The incidence of ipsilateral upper urinary tract stones after partial nephrectomy is higher than that of contralateral and bilateral stones.Intraoperative renal collecting system damage is a risk factor for secondary ipsilateral upper urinary tract stones after partial nephrectomy.

Glycoengineering was carried out in the mammalian cell line CHO for the production of pro-tein-based drugs.Firstly,the genome sequence of the Rosa26 locus of CHO cells was determined,the gRNA sequences were designed,and the landing pad was integrated into the Rosa26 locus of CHO cells by CRISPR/Cas9 technology.Three targeting vectors co-expressed by glycosyltransferases,which are β-1,4 galactosyltransferase(B4GALT1),α-2,6-sialyltransferase 1(ST6GAL1)and N-acetaminoglycosyl-transferase Ⅲ(GnT Ⅲ),were constructed by overlapping PCR and seamless ligation technology,and the three glycosyltransferase genes were integrated into the CHO Rosa26 locus by Cre enzyme-mediated cassette exchange technology.PCR confirmed that three glycosyltransferases had been successfully site-directed integrated into the Rosa26 site.The mRNA expression levels of the three glycosyltransferases were more than 50 000-fold by qRT-PCR,and the protein expression levels of the three glycosyltrans-ferases were more than 4-fold via western blotting(P＜0.001).A CHO-engineered cell line with three glycosyltransferases integrated into Rosa26 site was successfully constructed.

Reporting guidelines are structured checklists for researchers to follow when reporting spe-cific types of studies.As researches conducted in real-world settings to address practical issues,implementa-tion research has stringent requirements for the replicability of result and the transparency of reporting,making its reporting guidelines particularly important.This paper systematically introduces the reporting guidelines in the field of implementation science,outlines their classification systems and scopes of applica-tion,and focuses on explaining the core characteristics and functions of five key reporting guidelines,inclu-ding the Standards for Reporting Implementation Studies(StaRI),Reporting guidelines for implementation and operational research,the Template for Intervention Description and Replication(TIDieR),the Frame-work for Reporting Adaptations and Modifications-Enhanced(FRAME),and recommendations for specifying and reporting implementation strategies.Furthermore,combined with the PEDALs research paradigm in im-plementation science,this paper further clarifies the specific application pathways for reporting guidelines and discusses directions for refinement,aiming to provide references for researchers to select appropriate reporting guidelines.

Objective:To explore the application effect of early enteral nutrition combined with optimized blood glucose management in patients with stress hyperglycemia after cardiac surgery.Methods:A study was conducted to construct an early enteral nutrition and blood glucose optimization management plan for patients with stress hyperglycemia after cardiac surgery.A prospective analysis was conducted from May 2022 to May 2023 in the Cardiothoracic Surgery Intensive Care Unit(CICU)of a tertiary hospital in Shanghai.200 patients with stress hyperglycemia after cardiac surgery were divided into control group(n=100)and observation group(n=100)by random number table method.The control group received routine enteral nutrition and blood glucose management plan,while the observation group received early enteral nutrition combined with blood glucose optimization management plan.Nutrition related outcome indicators,blood glucose management quality indicators,and patient prognosis indicators were compared between two groups of patients.Results:After implementing the early enteral nutrition combined with optimized blood glucose management plan,the nutritional indicators(serum prealbumin,hemoglobin,and 7-day calorie compliance rate)of the observation group were higher than those of the control group,and the differences were statistically significant(P<0.05);The maximum blood glucose fluctuation amplitude,insulin use time,and incidence of hypoglycemia in the observation group were significantly lower than those in the control group(P<0.05),and the time within the glucose target range was significantly higher than that in the control group,with statistical significance(P<0.05);The mechanical ventilation time,ICU stay time,and total hospital stay in the observation group were significantly lower than those in the control group,and the differences were statistically significant(P<0.05).Conclusions:Early enteral nutrition combined with optimized blood glucose management can effectively improve the nutritional status of patients with stress hyperglycemia after cardiac surgery,reduce blood glucose fluctuations,improve blood glucose management quality,and promote patient outcomes and prognosis.