BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Objective To explore the relationship between preoperative coronary angiography and postoperative acute kidney injury (AKI) in cardiac surgery. Methods The clinical data of patients who underwent coronary angiography within 30 days before cardiac surgery in the First Affiliated Hospital of Xi’an Jiaotong University from January 2015 to April 2019 were retrospectively analyzed. Univariate analysis and multivariate logistic regression analyses were used to explore the relationship between the interval from preoperative coronary angiography to cardiac surgery and postoperative AKI. Results Finally 1 112 patients were collected, including 700 males and 412 females, with a median age of 61 (55, 66) years. The incidence of postoperative AKI was 40.8% (454/1 112), of which grade 2-3 AKI accounted for 11.9%. Multivariate analysis showed that age (OR=1.049, 95%CI 1.022-1.077, P<0.001), body mass index (OR=1.065, 95%CI 1.010-1.123, P=0.020) and time interval between preoperative coronary angiography and cardiac surgery within 24 hours (OR=1.625, 95%CI 1.116-2.364, P=0.011) were independent predictors of postoperative AKI. Patients who underwent coronary angiography within 24 hours before surgery had a 10.6% higher incidence of postoperative AKI compared to those who underwent angiography ≥24 hours before surgery (P=0.004). Patients who underwent valve surgery with or without coronary artery bypass grafting (CABG) had a higher risk of AKI than those who only underwent CABG. The in-hospital stay of patients who developed AKI was 2 days longer than those without AKI. However, undergoing coronary angiography within 24 hours before cardiac surgery did not prolong the length of ICU stay or hospital stay, nor did it increase the risk of death or renal failure after the operation. Conclusion Undergoing coronary angiography within 24 hours before cardiac surgery increases the risk of postoperative AKI.

Objective:To explore the core issues in the implementation of"packaged payment"in China's compact county medi-cal community,in order to provide useful references for the innovative reform of medical insurance payment methods in compact coun-ty medical community.Methods:By constructing the problem system through the macro model of the health system,analyzing the re-lated literature using multidimensional scale analysis and social network analysis,and comprehensively evaluating the results using the entropy-weighted TOPSIS method,it summarizes the core issues of"packaged payment"in compact county medical community.Results:There are core issues in China's compact county medical community,such as inadequate distribution of benefits and incen-tive and constraint mechanisms within the medical community(Ci= 1.000),lack of effective supervision and assessment mechanism for medical communities(Ci= 0.732),suppressed quality and efficiency of medical services(Ci= 0.652),lagging medical informatiza-tion construction(Ci= 0.595),and incomplete supporting policy measures(Ci= 0.579).Conclusion:The"packaged payment"of com-pact county medical community can be optimized from the following three aspects:a multi-level collaborative incentive mechanism should be improved to ensure the service quality and efficiency;optimize the total amount calculation method and improve the de-tailed supporting measures;accelerate information construction and strengthen supervision and assessment management.

Although immunotherapy has made a breakthrough in the treatment of cancer,the emergence of drug resistance has limited be-nefits in most patients,and reversing immunotherapy resistance remains a hotly debated and unresolved issue.The tumor microenviron-ment(TME)comprises a large number of T lymphocytes.During the biological processes of proliferation,activation,and the effect of tumor-infiltrating lymphocytes(TILs),TILs face severe local metabolic stress,resulting in metabolic reprogramming to meet the markedly increased energy demand and biosynthesis requirements.This process of adaptive changes in the metabolic pattern is closely related to the pheno-type and function of TILs,affecting immunotherapy efficacy and mediating immunotherapy resistance.In recent years,with the study of TIL metabolism and the search for specific metabolic regulatory points,targeting the TIL metabolic pathway could restore the tumor-killing func-tion and reverse immunotherapy resistance.This review explores the relationship between the metabolic reprogramming of TILs and im-mune resistance,and provides a new strategy for reversing immune resistance.

Objective:To investigate the value of 18F-FDG PET/CT combined with conventional imaging modalities in the evaluation of the depth of tumor invasion, regional lymph node metastasis, distant organ and lymph node metastasis (TNM staging), and the adjacent structure invasion of rectal cancer. Methods:Fifty-four patients (28 males, 26 females, age (65.8±11.0) years) with pathologically confirmed rectal cancer admitted to the Affiliated Qingdao Central Hospital of Qingdao University between September 2019 and June 2021 were retrospectively analyzed. 18F-FDG PET/CT examination, conventional imaging modalities including high-resolution MRI (HR-MRI), chest CT plain scan, upper abdominal MRI or CT plain scan+ enhanced examination were performed within 2 weeks before or after the rectal cancer being confirmed. The TNM staging and adjacent structural invasions including circumferential resection margin (CRM), extramural vascular invasion (EMVI), anal sphincter complex involvement were evaluated by 18F-FDG PET/CT and conventional imaging modalities separately or in combination, and those results based on imaging were compared with the pathological results or clinical follow-up results. χ2 test was used to compare the differences of diagnostic sensitivity, specificity and accuracy between the 18F-FDG PET/CT or conventional imaging modalities and combined examination. Results:The accuracy for T staging and the sensitivity and accuracy for N staging of the combined examination were 96.30%(52/54), 98.65%(73/74) and 93.91%(185/197), respectively, which were significantly higher than those of 18F-FDG PET/CT (85.19%(46/54), 66.22%(49/74), 81.73%(161/197); χ2 values: 3.97, 26.88, 13.66, all P<0.05). The specificity (91.06%, 112/123) and accuracy of the combined examination for N staging were higher than those of the conventional imaging modalities (77.24%(95/123), 83.76%(165/197); χ2 values: 8.81, 10.23, both P<0.05). The sensitivity and accuracy of the combined examination for M staging were higher than those of the conventional imaging modalities (97.01%(65/67) vs 73.13%(49/67), 95.95%(71/74) vs 68.92%(51/74); χ2 values: 15.05, 18.66, both P<0.001). The sensitivities of the combined examination in evaluating CRM and EMVI were 100%(22/22) and 95.00%(19/20), and the accuracies were 98.15%(53/54) and 96.30%(52/54), all of which were higher than those of 18F-FDG PET/CT (CRM: 54.55%(12/22), 74.07%(40/54); EVMI: 30.00%(6/20), 74.07%(40/54); χ2 values: 12.94, 13.08, 18.03, 10.56, all P<0.01). The accuracy of the combined examination in evaluating EMVI was higher than that of the conventional imaging modalities (85.19%(46/54); χ2=3.97, P=0.046). Conclusion:18F-FDG PET/CT combined with conventional imaging modalities can improve the diagnostic efficacy for TNM staging and assessment of adjacent structural invasion in rectal cancer.

Objective To evaluate the clinical value of optic nerve sheath diameter(ONSD)measured on thin-slice CT scan in the diagnosis and prognostic assessment of cerebral venous sinus thrombosis(CVST).Methods The clinical data of patients with CVST,who were admitted to the First Affiliated Hospital of Nanjing Medical University of China to receive treatment from January 1,2016 to December 31,2022,were retrospectively analyzed.The difference in ONSD was compared between CVST patients and normal population,the postoperative changes in ONSD was analyzed.Results A total of 49 patients with CVST(CVST group)and 49 normal persons having no brain disorders(control group)were enrolled in this study.In CVST group,the preoperative ONSD was(5.33±0.50)mm,which was significantly higher than(4.40±0.40)mm in control group(P＜0.001),the postoperative ONSD remarkably decreased to(4.98±0.59)mm(P＜0.01).The difference value between postoperative ONSD and preoperative ONSD in the patients receiving pure anticoagulation treatment was not statistically significant different from that in the patients receiving endovascular treatment[(-0.43±0.22)mm vs.(-0.40±0.42)mm,P=0.84].The preoperative ONSD in the patients having intracranial hemorrhage and in the patients having no intracranial hemorrhage was(5.26±0.51)mm and(5.41±0.49)mm respectively(P=0.31),and the difference value between postoperative ONSD and preoperative ONSD was(-0.39±0.40)mm and(-0.45±0.25)mm respectively(P=0.66).At the three-month follow-up visit,the difference in ONSD between the patients having a good prognosis(mRS score being 0-2 points)and the patients having a poor prognosis was not statistically significant(P＞0.05).Conclusion ONSD that is measured on plain head CT scan can be used as a response indicator of elevated intracranial pressure in CVST patients,which can be used to monitor the changes in intracranial pressure before and after treatment,but its value in assessing the curative efficacy of different therapeutic methods needs to be further explored.

The aim of this study is to establish a simple and accurate method for vaccine immune e-valuation of porcine pseudorabies virus.In this research,PRV-gD recombinant protein was ex-pressed from mammalian cell HEK-293F as coating antigen,and then the reaction conditions of gD-iELISA were optimized according to checkerboard titration method.The gD-iELISA was used to detect the antibody levels of 211 clinical pig serum samples and the consistency with the neu-tralizing antibody levels wasanalyzed.The results showed that the antigen coating concentration was 0.90 mg/L;the serum to be detected was diluted 1∶100 and incubated at 37 ℃ for 30 min;goat anti-pig IgG-HRP antibody was diluted 1∶55 000 and incubated at 37 ℃ for 30 min;TMB sub-strate was developed at 37 ℃ for 20 min.The method could detect 1∶6 400 diluted PRV positive serum.The results of CSFV,PRRSV,PCV-2,PEDV and FMDV positive sera were all negative by gD-iELISA,and there was no cross-reaction between the method and the above positive sera.The coincidence rate of gD-iELISA and commercial kits was 95.26％,and the intra-and inter-batch co-efficients of variation were both less than 10％.Correlation analysis showed that the correlation coefficient(r)between gD antibody level and neutralizing antibody level was significantly greater than that of gB antibody level,and the gD antibody level had a good linear relationship with the neutralizing antibody level.The results indicated that gD-iELISA was more suitable for vaccine im-mune evaluation of PRV than gB-iELISA.Therefore,the method will have a good prospect of ap-plication in the immunization control of the PRV.

Purpose: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. Methods: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. Results: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. Conclusions This study aimed to improve clinicians’ ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

ObjectiveTo explore the mechanism of Renshen Baidusan in repairing intestinal mucosa in ulcerative colitis （UC） by regulating autophagy to scavenge peroxides. MethodThe mouse model of UC was induced by free drinking of 3.0% dextran sulphate sodium （DSS） solution. Sixty male C57BL/6J mice were randomized into normal， model， mesalazine （0.3 g·kg^-1）， and high-， medium-， and low-dose （12.35， 8.22， 4.11 g·kg^-1， respectively） Renshen Baidusan groups （n=10）. The mice were administrated with corresponding drugs by gavage for 7 consecutive days. The colon tissue was stained with hematoxylin-eosin （HE） to reveal the pathological changes， and Alcian blue-Periodic acid Scheff （PAS/AB） staining was employed to observe the goblet cell changes. The fluorescence expression of reactive oxygen species （ROS） in the colon tissue was detected by the immunofluorescence assay. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were measured by the biochemical methods. Western blot was employed to determine the expression levels of proliferating cell nuclear antigen （PCNA）， microtubule-associated protein 1 light chain 3 （LC3）， leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5）， and p62. ResultDestroyed mucosal epithelial structure， intestinal gland destruction， loss of goblet cells， and massive infiltration of inflammatory cells appeared in the model group. Compared with the normal group， the model group showed increased tissue damage injury （TDI） score of the colon tissue， decreased SOD activity and LC3Ⅱ/Ⅰ， PCNA value， and elevated levels of p62， MDA， ROS， and LGR5 （P<0.05）. Compared with the model group， different doses of Renshen Baidusan decreased the TDI score， promoted the generation of new goblet cells， elevated the levels of PCNA， LGR5， SOD， and LC3Ⅱ/Ⅰ， and lowered the levels of p62， MDA， and ROS （P<0.05）. Moreover， the low dose group showed the best performance （P<0.05）. ConclusionRenshen Baidusan can promote intestinal epithelial repair by activating intestinal autophagy， alleviating oxidative stress， and promoting intestinal stem cell proliferation and differentiation.

ObjectiveTo explore the mechanisms of internal treatment （Renshen Baidusan）， external treatment （Yurui Enema）， and combination of the two methods in treating intestinal mucosal injury in the rat model of ulcerative colitis （UC） from the changes of phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt）/nuclear factor-κB （NF-κB） pathway. MethodFifty SPF-grade SD rats were randomized into blank， model， Renshen Baidusan （15.6 g·kg^-1）， Yurui Enema （25 g·kg^-1）， and combined treatment （15.6 g·kg^-1 Renshen Baidusan + 25 g·kg^-1 Yurui Enema） groups （n=10）. The rat model of UC was established in other groups except the blank group by 2，4， 6-trinitrosulfonic acid （TNBS）/ethanol. The rats were administered with corresponding drugs once a day for 14 consecutive days since the 8th day after modeling. The histopathological changes of colon were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interferon （IFN）-γ， interleukin （IL）-4， and IL-10 in the colon tissue. The apoptosis of colon epithelial cells was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The location and expression of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， TNF-α， and IL-6 in the colon tissue were examined by immunohistochemistry. Real-time quantitative fluorescence polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of the proteins in the PI3K/Akt/NF-κB pathway in the colon tissue. ResultIn the model group， HE staining showed a large number of inflammatory cell infiltration in the mucosa and submucosa. Compared with the blank group， the model group showed elevated levels of TNF-α and IFN-γ and lowered levels of IL-4 and IL-10 in the colon tissue， increased apoptosis rate of colon epithelial cells， increased positive expression of Bax， TNF-α， and IL-6， and decreased positive expression of Bcl-2 （P<0.05）. Moreover， the model group showed up-regulated mRNA levels of PI3K， Akt， and NF-κB and protein levels of PI3K， p-PI3K， Akt， p-Akt， p65， p-p65， Bax， and cleaved Caspase-3， increased Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios， and down-regulated protein levels of NF-κB suppressor protein α（IκBα）， Bcl-2， and Caspase-3 in the colon tissue （P<0.05）. Compared with the model group， the internal treatment， the external treatment， and the combination （referred to as the three groups） alleviated the colonic mucosal injury， lowered the levels of TNF-α and IFN-γ and elevated the levels of IL-4 and IL-10 in the colon tissue， decreased the apoptosis rate of colon cells， inhibited the positive expression of Bax， TNF-α， and IL-6， and promoted the positive expression of Bcl-2 （P<0.05）. Furthermore， the combination group down-regulated the mRNA level of PI3K （P<0.05）. The three groups down-regulated the mRNA levels of Akt and NF-κB and the protein levels of p-PI3K， Akt， p-Akt， p65， p-p65， Bax， and cleaved Caspase-3 in the colon tissue， decreased the Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios， and up-regulated the protein levels of IκBα， Bcl-2， and Caspase-3 （P<0.05）. ConclusionRenshen Baidusan， Yurui Enema， and their combination may inhibit the activation of PI3K/Akt/NF-κB signaling pathway and regulate the expression of genes and proteins related to this pathway to achieve anti-inflammatory and anti-apoptotic effects， thus restoring the intestinal mucosal barrier function of UC rats.