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.

BACKGROUND:Studies have found that nicotine can activate the dopamine system,slowing the progression of Parkinson's disease,but the specific mechanism is still unclear.Research on the neuroprotective mechanism of nicotine in animal models of Parkinson's disease is lacking. OBJECTIVE:To investigate the neuroprotective effect of nicotine on rotenone-induced Parkinson's disease in mice. METHODS:Twenty-eight C57BL/6 mice were randomly divided into vehicle group,rotenone group,autophagy agonist group and nicotine group,with seven mice in each group.Dopaminergic nerve damage was induced by rotenone in C57BL/6 mice,and the autophagy agonist(rapamycin)or nicotine was given before modeling.The spatial exploration function of the mice was observed by open field test.Western blot and Q-PCR were used to detect the expression of α-synuclein,autophagy related factors Beclin-1 and P62,and apoptosis-related factors Bax,Bcl-2 and Cleaved-caspase3 in the nigra of each group.The deposition of mitochondria,autophagosomes and lipofuscin in nigra cells were observed by transmission electron microscopy.The survival of neurons was observed by Nissl staining.The expression of tyrosine hydroxylase was observed by immunofluorescence and immunohistochemical staining. RESULTS AND CONCLUSION:The open field test showed that the distance,average speed and time of movement were reduced in the rotenone group compared with the solvent group.Compared with the rotenone group,the exercise distance,average speed and exercise time of mice were increased in the nicotine group and autophagy agonist group(P＜0.05).The results of immunofluorescence and immunohistochemistry showed that the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase in the rotenone group decreased compared with that in the solvent group.Compared with the rotenone group,the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase were increased in the nicotine group and autophagy agonist group.Western blot and Q-PCR results showed that compared with the solvent group,the expressions of α-synuclein and P62 in the rotenone group were increased,while Beclin-1 expression was decreased(P＜0.05);compared with the rotenone group,the expression of α-synuclein and P62 decreased in the nicotine group and autophagy agonist group,and the expression of Beclin-1 increased(P＜0.05).Compared with the solvent group,the expressions of Bax and Cleaved caspase3 were increased and Bcl-2 expression was decreased in the rotenone group(P＜0.05);compared with the rothenone group,the expressions of Bax and Cleaved-caspase3 were decreased and the expression of Bcl-2 was increased in the nicotine and autophagy agonist groups(P＜0.05).To conclude,nicotine may have a dopaminergic neuroprotective effect on rotenone-induced Parkinson's disease mouse models by improving autophagy dysfunction and reducing apoptosis.

Objective:To conduct a scoping review to analyse the types, performance, advantages and disadvantages of cognitive function assessment tools for ICU patients, to provide a reference for the evaluation of cognitive function in ICU patients in future.Methods:A scoping review study was conducted, literature on cognitive function assessment tools for ICU patients in 9 domestic and foreign databases including China National Knowledge Infrastructure, Wanfang Database, VIP Database, China Biology Medicine disc, PubMed, Web of Science, Cochrane Library, Embase and CINAHL were systematically searched. The search period was from the establishment of the database to May 20, 2024. Literature was independently screened by 2 researchers and relevant information was extracted and summarized.Results:Totally 17 studies were included, with 9 tools for assessing cognitive function in ICU patients, including 6 questionnaires, 1 test battery, 1 assessment software, and 1 telephone interview questionnaire. All of above were generalizable tools, except for the Chinese and English versions of the John-Hopkins Adapted Cognitive Exam as ICU-specific tools. The Mini-Mental State Examination was the most widely used assessment scale.Conclusions:Appropriate assessment tools should be selected according to the specific clinical setting, but there is still a lack of specialized and standardized assessment tools for cognitive dysfunction in ICU patients. In the future, standardized tools which fit our cultural context for evaluating cognitive function in ICU patients should be developed.

The aim of this study was to investigate the correlation between porcine epidemic diar-rhea virus(PEDV)S1 IgG antibody levels and neutralizing antibody potency in sow sera.Sera from 5 PEDV-infected farms with a clear immune background,5 non-infected farms and 5 infected farms with an unclear immune background,and sera from return-fed reserve pigs,totaling 716 copies,were collected and measured,and the correlation between PEDV S1 IgG antibodies and neutralizing antibodies was analyzed.The results showed that the PEDV S1 IgG and neutralizing antibodies of sow sera showed highly significant positive correlation,the correlation coefficient was 0.892(P＜0.000 1).Previous studies have shown that the level of PEDV neutralizing antibodies in sow serum correlates with the ability of piglets'maternal antibodies to resist PEDV infection.Therefore,the a-bility of maternal antibodies against PEDV in piglets can be evaluated by detecting PEDV S1 IgG antibodies in the serum of sows.In 10 PEDV-infected farms,the neutralizing antibodies to PEDV in the sera of sows after immunization were generally high,and the S1 IgG antibodies were also high,and their S/P values were higher than 3.5 in 66.9％of the farms(347/519),and the highest anti-body levels were found in the four farms in which PED did not occur,whereas the neutralizing an-tibodies in the immunized sows in the five PEDV-uninfected farms were generally low,and their S1 IgG antibodies were also low,and only 8.1％(13/161)having S/P values higher than 3.5.The re-sults suggest that most sows in PEDV-infected farms can provide good immunoprotection to pig-lets after immunization,while pigs in PEDV-uninfected farms need further immunization if they need to achieve a higher level of immunoprotection.The present study provides a substantial clini-cal basis for the use of PEDV S1 IgG antibody levels to assess the effectiveness of PEDV antibody protection in swine herds.

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.

Biapenem is a carbapenem antibiotic， and can be used for the treatment of sepsis， pneumonia， lung abscess， chronic respiratory lesions secondary infection， complex urinary tract infection and pyelonephritis， etc. This article reviewed the studies on the pharmacokinetics， pharmacodynamics and therapeutic drug monitoring （TDM） of biapenem. The pharmacokinetic parameters of biapenem are not significantly different in healthy subjects， and there is no accumulation after multiple doses of biapenem. However， there are large differences in pharmacokinetic parameters in patients with severe disease and patients with abnormal renal function compared with healthy subjects， which leads to conventional treatment regimens not achieving the desired outcome. In terms of pharmacodynamics， biapenem can improve the rate of reaching the target value by increasing the frequency of administration and prolonging the infusion time. For patients with anuria in end-stage renal disease， dosing intervals can be extended to avoid drug accumulation. However, for patients with severe infection, a daily dose of 1.2 g still can not control infections caused by Acinetobacter baumannii or Pseudomonas aeruginosa, which limits its use in patients with severe disease. It is recommended to implement TDM in severe patients and patients with abnormal renal function， and explore the best dosing regimen for biapenem in combination with pharmacokinetic models to ensure that the time that the free blood concentration of biapenem remains above minimum inhibitory concentration as a percentage of the time between doses （%fT＞MIC） is within the effective range，so that biapenem can exert a greater efficacy in severe patients and patients with abnormal renal function. For medical institutions that cannot carry out TDM， the efficacy of biapenem can be maximized by increasing the frequency of administration and prolonging the infusion time. For infections caused by P. aeruginosa， A. baumannii and Serratia marcescens with high drug resistance rates， it is recommended to combine or replace other antibiotics.

Alzheimer's disease （AD） is a deleterious neurodegenerative disorder， which has become a significant public health concern and economic burden. The pathogenesis of AD is complex and involves several hypotheses such as amyloid β-protein （Aβ） deposition， Tau protein hyperphosphorylation， oxidative stress， and inflammation. There is an urgent need for a holism-based comprehensive intervention with multi-pathway， multi-level， and multi-target characteristics， which demonstrates the unique advantage of traditional Chinese medicine （TCM）. Therefore， it is of great significance to conduct and promote research on TCM treatment of AD. Danggui Shaoyaosan （DSS） from the Synopsis of Golden Chamber （《金匮要略》） by ZHANG Zhongjing （150 AD-219 AD） was originally designed for reliving gynecological ailments. It is a classic TCM formula that modulates liver and spleen and dispels blood stasis and water retention. Since the late 1980s when Japanese researchers reported its therapeutic effect on AD， it has been widely used in the clinic with clear effects. The elucidation of the mechanism of this formula helps exert its effects. Hereby， this paper reviewed relative research progress and made an analysis in terms of attenuating aberrant accumulation of Aβ and hyperphosphorylated Tau protein， anti-inflammatory and antioxidant activities， mediating neurotransmitters， ameliorating lipid metabolism， modulating gut microbiota， reduced neuron apoptosis， decreasing intracellular Ca²⁺ overloading， and increasing the expression of estradiol. This paper is expected to provide references for understanding the scientific connotation of DDS in the treatment of AD and lay a solid foundation for further investigation.

ObjectiveTo investigate the protective effect of Danggui Shaoyaosan （DSS）-contained serum on β-amyloid （Aβ）_1-40-injured rat adrenal pheochromocytoma PC12 cells and its mechanism in regulating ubiquitin-proteasome pathway （UPP）. MethodAβ_1-40 was used to intervene PC12 cells to prepare the cell models of Alzheimer's disease （AD）， and the experiment was divided into the blank， model， and DSS-contained serum high， medium， and low-dose groups （10%， 5%， and 2.5%）. Cell viability and apoptosis were detected using cell counting kit-8 （CCK-8） method and flow cytometry， respectively. The content of Aβ and p-Tau protein was determined by enzyme-linked immunosorbent assay （ELISA）. The ubiquitin （Ub）， ubiquitin ligase E3 （E3）， 26S proteasome， ubiquitin carboxyl terminal hydrolase1 （UCHL1）， and UCHL3 protein expressions of UPP were displayed using immunofluorescence cytochemistry （ICC）， and the mRNA and protein expression levels of Ub， E3-parkin， 26S， UCHL1， and UCHL3 were determined by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultThe data of the CCK8 experiment verified that 5 μmol·L^-1 and 48 hours were the optimal conditions for modeling Aβ_1-40-injured PC12 cells. As compared with the blank group， the cell viability rate in the model group decreased （P<0.05） with an increased apoptosis rate （P<0.05）， the content of Aβ and p-Tau contents was elevated （P<0.05）， the mRNA and protein expression levels of Ub increased， and the mRNA and protein expression levels of 26S， E3， and UCHL1+3 decreased （P<0.05）. As compared with the model group， the cell viability rate in the DSS-contained medium-dose group increased （P<0.05）， whereas the apoptosis rate in each DSS-contained group decreased （P<0.05）. The content of Aβ in each DDS-contained group decreased （P<0.05）， and the content of p-Tau in the DDS-contained high and medium-dose groups decreased （P<0.05）. The mRNA expression level of Ub decreased， and that of 26S increased in each DDS-contained group （P<0.05）. The mRNA expression level of UCHL1 in the DDS-contained medium-dose group increased （P<0.05）， and the mRNA expression levels of E3 and UCHL 3 in the DDS-contained high and medium-dose groups increased （P<0.05）. The protein expression level of Ub in each DDS-contained group decreased， and the protein expression levels of 26S， E3， and UCHL1+3 in the DDS high and medium-dose groups increased. The DSS-contained serum medium-dose group exerted the optimal effect. ConclusionDSS-contained serum can increase cell viability rate， reduce cell apoptosis rate， eliminate Aβ and p-Tau protein deposits， and exert protective effects on Aβ_1-40-injured PC12 cells. Its mechanism may involve UPP via decreasing the expression of Ub and increasing that of 26S， E3， UCHL1， and UCHL3.

Objective: To analyze the recent postoperative and long-term postoperative complications of open-splenectomy and disconnection in patients with portal hypertension. Methods: There were 1 118 cases with portal hypertension who underwent open splenectomy and azygoportal disconnection from April 2010 to September 2015 at Department of Surgery, People′s Liberation Army 302 Hospital. Retrospective case investigation and telephone follow-up were conducted in October 2016. All patients had history of upper gastrointestinal bleeding before operation. Short-term complications after surgery were recorded including secondary laparotomy of postoperative abdominal hemostasis, severe infection, intake disorders, liver insufficiency, postoperative portal vein thrombosis and perioperative mortality. Long-term data including postoperative upper gastrointestinal rebleeding, postoperative survival rate and incidence of postoperative malignancy were recorded, too. GraphPad Prism 5 software for data survival analysis and charting. Results: Postoperative short-term complications in 1 118 patients included secondary laparotomy of postoperative abdominal hemostasis(1.8%, 21/1 118), severe infection(2.9%, 32/1 118), intake disorders(1.0%, 11/1 118), liver dysfunction (1.6%, 18/1 118), postoperative portal vein thrombosis(47.1%, 526/1 118)and perioperative mortality(0.5%, 5/1 118). After phone call following-up, 942 patients′ long-term data were completed including 1, 3, 5 years postoperative upper gastrointestinal rebleeding rate(4.4%, 12.1%, 17.2%), 1, 3, 5-year postoperative survival rate(97.0%, 93.5%, 90.3%); the incidence of postoperative malignant tumors in 1, 3 and 5 years were 1.7%, 4.4% and 6.2%. Conclusions Reasonable choosing of surgical indications and timing, proper performing the surgery process, effective conducting perioperative management of portal hypertension are directly related to the patient′s short-term prognosis after portal hypertension. Surgical intervention can reduce the rates of patients with upper gastrointestinal rebleeding, improve survival, and do not increase the incidence of malignant tumors.

Objective From the perspective of making full use of database comparison function, giving certain guidelines to analyze mixed DNA profile,compare database,screen comparison results. Methods Using CPI to describe the identification of mixed DNA profile.Using CPBI to estimate reliability of individual samples being included. Results When CPI is less than 10-7, mixed DNA Profile is worth to be compared in database.When the number of alleles at one locus is more than 2, retain an additional allele will not reduce identification too much. According to the CPBI of the included samples,we can find the most reliable sample.