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.

ObjectiveTo analyze the factors influencing meropenem-related liver injury （MRLI） and to explore their clinical predictive value. MethodsA retrospective case-control study was conducted， and the Chinese Hospital Pharmacovigilance System （CHPS） was used to establish a retrieval scheme. A total of 1 625 hospitalized cases using meropenem from January 2018 to December 2022 were collected. Patients were divided into case group （n=62） and control group （n=1 563） based on the presence or absence of liver injury. Clinical data and laboratory indicators from both groups were collected and analyzed. The t-test was used for comparison of normally distributed continuous data between the two groups， while the Mann-Whitney U test was used for comparison of continuous data not conforming to a normal distribution. The chi-square test was used for comparison of categorical data between the two groups. A multivariate Logistic regression analysis was performed to identify the influencing factors for MRLI. A Logistic regression equation was established， and the predictive value of these factors was assessed using the receiver operating characteristic （ROC） curve. ResultsThe results of univariate analysis indicated that the rates of male patients， hypoproteinemia， shock， intensive care unit （ICU） admissions， sepsis， and liver， gallbladder， and cardiovascular diseases， the levels of alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， aspartate aminotransferase （AST）， creatinine （CREA）， and procalcitonin （PCT）， and the number of hospitalization days were significantly higher in the case group than in the control group （P<0.05）， and that the platelet levels in the case group were significantly lower than those in the control group （P<0.05）. The multivariate Logistic regression analysis showed that male sex （odds ratio ［OR］=2.080， 95% confidence interval ［CI］： 1.050 — 4.123， P=0.036）， admission to the ICU （OR=8.207， 95%CI： 4.094‍ ‍—‍ ‍16.453， P<0.001）， comorbidity with gallbladder disease （OR=8.240， 95%CI： 3.605‍ ‍—‍ ‍18.832， P<0.001）， ALP （OR=1.012， 95%CI： 1.004‍ ‍—‍ ‍1.019， P=0.004）， GGT （OR=1.010， 95%CI： 1.005‍ ‍—‍ ‍1.015， P<0.001）， and PLT （OR=0.997， 95%CI： 0.994‍ ‍—‍ ‍0.999， P=0.020） were the influential factors for MRLI. The areas under the ROC curve of ALP， GGT， and PLT were 0.589， 0.637， and 0.595， respectively， and the AUC of them combined was 0.837. ConclusionMale sex， ICU admission， comorbidity with gallbladder disease， increased ALP， increased GGT， and decreased PLT were influencing factors for MRLI， and a combination of factors has a better predictive value for the occurrence of MRLI.

To analyze the biological characteristics of Pasteurella multocida in bovine respiratory tract and its prevalence in large-scale cattle farms,bacterial isolation,culture,and morphological observation were conducted on the lungs and liver samples of dead cows suffering from respiratory diseases in Hohhot,Inner Mongolia.The isolated strains were studied through biochemical testing,16S rRNA gene sequencing,specific primer PCR identification,capsule serotyping,pathogenicity testing,virulence gene testing,drug sensitivity testing,and drug resistance gene detection methods.The results showed that six strains of Pasteurella multocida serotype A were isolated and identi-fied from the lungs of diseased and dead cows.After sequencing the 16S rRNA sequence of the bac-teria,it was found that the six strains of Pasteurella multocida had the closest genetic relationship with the Chongqing isolate CQ2(CP033599.1).The results of mouse pathogenicity test and viru-lence gene detection showed that all isolates were pathogenic and carried at least 16 or more related virulence genes such as exbB,nanB,sodC,oma 87,etc.,but no hsf1 and toxA were detected.The results of drug sensitivity tests and resistance gene detection showed that the isolated strains were sensitive to different degrees of antibiotics such as ciprofloxacin,ofloxacin,and cefotaxime.They were resistant to streptomycin,clindamycin,and lincomycin,and resistance genes of str A,strB,and tet(H)were detected.The results indicate that there is a certain correlation between the pathoge-nicity and virulence genes,drug resistance phenotype,and drug resistance genes of Pasteurellamultocida type A in cattle.It is recommended to use quinolones(such as ciprofloxacin)and cepha-losporins(such as cefotaxime)antibacterial drugs in clinical practice,which can provide scientific basis and prevention and control plans for the prevention and treatment of respiratory diseases caused by Pasteurella multocida in cattle farms,and lay a foundation for the epidemiological mo-nitoring of bovine respiratory multocida pasteurellosis.

Objectives:To clarify the radiological anatomy features of adrenal arteries derived from digital subtraction angiography(DSA)in patients with primary aldosteronism(PA). Methods:The DSA images of 119 patients diagnosed with PA and underwent percutaneous selective adrenal artery embolization from January 2018 to December 2019 at the 2nd Affiliated Hospital of Nanchang University were retrospectively analyzed,and the number,origin,distribution,angle and diameter of adrenal arteries were analyzed. Results:The mean age of 119 PA patients was(49±11)years,with 71(59.7%)males,and at least one adrenal artery was successfully identified in all patients,a total of 192 adrenal arteries were analyzed.There were 20(10.4%)upper,40(20.8%)middle and 132(68.8%)lower adrenal arteries.Adrenal arteries originating from renal arteries accounted for 42.7%(82/192),adrenal arteries originating from the abdominal aorta accounted for 37.5%(72/192),and those from the inferior diaphragmatic arteries accounted for 19.8%(38/192).72.8%(83/114)of left adrenal arteries and 60.3%(47/78)of right adrenal arteries distributed at the level of the first lumbar vertebrae.28.1%(54/192)adrenal arteries distributed at the level of the second lumbar vertebrae,and 4.2%(8/192)adrenal arteries at the level of the 12th thoracic vertebrae.The angle range of left adrenal arteries intersecting with the origin arteries was 35.90° to 160.07°(renal artery),27.08° to 171.99°(accessory renal artery),0° to 158.70°(abdominal aorta);for right adrenal arteries,it was 18.43° to 172.53°(renal artery),69.26° to 114.62°(accessory renal artery),12.32° to 232.85°(abdominal aorta),respectively.The average diameters of left and right adrenal arteries were(0.98±0.45)mm and(1.27±0.42)mm,respectively. Conclusions:This study provides more detailed radiological anatomy data of adrenal arteries in PA patients.As a supplement to human anatomical features,the described data can provide practical guidance for adrenal artery interventional treatment.

Objective:To consolidate the current evidences regarding the efficacy of vitamin D supplementation in age-related sarcopenia.Methods:In this systemic review, a comprehensive literature search of scientific research including journal articles and academic dissertations was performed in prominent databases such as PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Database platforms, spanning from January 31, 2014 to January 31, 2024. Two search protocols integrating keywords and citation tracking were adopted to ensure comprehensiveness of the literature. Using “vitamin D” “ergocalciferols” “cholecalciferol” “sarcopenia” “muscle mass” “muscle strength” “myopenia” “muscle loss” “muscle reduction” “gait speed” “grip strength” “handgrip” as the main key words, focusing on the systematic reviews, meta-analyses of randomized controlled trials (RCT), and individual RCT, the scientific evidence of individual vitamin D intervention on age-related sarcopenia was evaluated and summarized. Research concerning particular disease conditions, children and adolescents, menopausal women, athletes and other specific populations were excluded.Results:A initial search yielded 2 448 articles in Chinese or English. A total of 8 systemic reviews/meta-analysis and 22 individual RCT literatures were included in the final analysis. Although some earlier lower-quality studies reported subtle improvements in skeletal muscle strength with vitamin D supplementation, high-quality systematic reviews/meta-analysis over the past three years had not shown significant positive effects of vitamin D intervention on sarcopenia and its breakdown parameters, such as skeletal muscle mass, muscle strength, and muscle function. Furthermore, the efficiency was influenced to some extent by the participants′ baseline status, such as muscle health and vitamin D nutritional status.Conclusions:Present evidence does not robustly support the efficacy of sole vitamin D supplement on age-related sarcopenia. High-quality clinical trials are imperative to accumulate more robust evidence in the future.

Objective To understand the research status and development trend in the field of molecular and cell biology of thyroid cancer.Methods Relevant literature published in the field of molecular and cell biology of thyroid cancer from January 1,2013 to December 31,2022 was obtained in the web of science core collection(WoSCC)according to the search conditions,and bibliometric and visual analysis were performed using the bibliometric software VOSviewer and Excel.Results A total of 1 627 literatures were included.Among them,113 papers were published in 2013,and 214 were published in 2022.The annual number of publications was on the rise.There were 9 274 authors in total,of whom 6 published no less than 10 literatures.There were a total of 2 042 institutions,of which the top 10 institutions were mostly Chinese universities.There were 68 countries in total,and the largest number of publications was China,followed by the United States.There were 513 journals in total,and the top 10 journals with the largest number of literatures were mainly in the field of oncology,followed by the field of endocrinology and metabolism.A total of 62 563 references from 5 887 journals were cited.The most co-cited journal was Journal of Biological Chemistry(1 608 times),and the most co-cited references was Molecular Pathogenesis and Mechanisms of Thyroid Cancer(89 times).Conclusion The field of molecular and cell biology of thyroid cancer is currently developing steadily.Ferroptosis,glycosylation,telomerase reverse transcriptase and oxidative stress are the research frontiers in this field.

Objective To investigate the predictive value of serum Nesfatin-1 and 25-hydroxyvitamin D3[25(OH)D3]levels for the short-term prognosis of status epilepticus(SE)in children.Methods A total of 104 children with SE admitted to the hospital from March 2020 to March 2023 were enrolled in the study,and the clinical data of the children were collected.According to the Glasgow outcome Scale(GOS)score at dis-charge,the children were divided into a good prognosis group(equal to 5 points)and a poor prognosis group(＜5 points).Univariate analysis and multivariate Logistic regression were used to analyze whether serum Nesfatin-1 and 25(OH)D3 levels were risk factors for poor short-term prognosis in children with SE.The re-ceiver operating characteristic(ROC)curve was drawn to analyze the predictive value of serum Nesfatin-1 and 25(OH)D3 levels for the short-term poor prognosis in children with SE.Results At discharge,85 children[81.73％(85/104)]with a GOS score of 5 were included in the good prognosis group,and 19 children[8.27％(19/104)]with a GOS score of＜5 were included in the poor prognosis group.There was no significant differ-ence in gender,age,previous history of epilepsy,and seizure types between the two groups(P＞0.05).There were significant differences in the duration of SE,the time from medication to seizure cessation,electroenceph-alogram(EEG)results,head CT results,and serum Nesfatin-1 and 25(OH)D3 levels between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that SE duration＞60 min,abnormal head CT results,serum Nesfatin-1 and 25(OH)D3 levels were independent risk factors for the short-term poor progno-sis of children with SE(OR=1.945,2.343,1.731,1.505;P＜0.05).The area under the ROC curve of serum Nesfatin-1 and 25(OH)D3 levels combined to predict poor short-term prognosis of children with SE was 0.840(95％CI:0.732-0.949),which was better than that of serum Nesfatin-1 and 25(OH)D3 levels alone[0.607(95％CI:0.453-0.761),0.742(95％CI:0.604-0.880)],respectively.Conclusion Serum Nesfatin-1 and 25(OH)D3 levels are risk factors for poor prognosis in children with SE,and the combination of them has high predictive value for poor prognosis in children with SE.

Objective·To evaluate the quality of clinical practice guidelines of obstructive sleep apnea(OSA)published worldwide.Methods·The guidelines of OSA were retrieved in PubMed,Embase,China National Knowledge Infrastructure(CNKI),Wanfang Data,SinoMed,MedSci,The Cochrane Library,and the websites such as Medlive,U.S.Preventive Services Task Force(USPSTF),National Institute for Health and Care Excellence(NICE),New Zealand Guidelines Group(NZGG),Scottish Intercollegiate Guidelines Network(SIGN),and Guidelines International Network(GIN)from establishment to December 2022.Two reviewers screened the literature and extracted the main information independently,using the Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ)and Reporting Items for Practice Guidelines in Healthcare(RIGHT)to evaluate the quality of the included OSA guidelines.Subgroup analysis was performed according to the publication regions of guidelines.The inter-evaluator consistency test was also performed and the results were expressed as the intra-class correlation coefficient(ICC).All the included guidelines were read entirely and the clinical questions they raised were summarized.Results·A total of 35 OSA guidelines were included.The ICC value of 0.975 showed a good inter-evaluator agreement.The results of AGREE Ⅱ showed that the average score of all guidelines was(63.60±16.45)%,with a minimum of 23.40%and a maximum of 91.67%.In the six domains,the scores of"Rigor of development"[(56.07±25.89)%]and"Applicability"[(53.57±15.52)%]were relative low.The average reporting rate of RIGHT of all the included guidelines was(67.84±20.03)%,with a minimum of 14.29%and a maximum of 94.29%,and the three domains with the lowest reporting rates were"Review and quality assurance"[(31.40±45.51)%],"Funding and conflict of interest declaration and management"[(56.43±33.95)%]and"Other aspects"[(56.19±36.85)%].Subgroup analysis showed that guidelines in Asian had a lower score in"Rigor of development"and a lower overall score of AGREE Ⅱ than the guidelines in America and Europe(both P<0.05),and the reporting rates in the domains of"Evidence"and"Other information"of RIGHT of the Asian guidelines were also lower than those in the guidelines in America and Europe(P<0.05).These guidelines focused on 42 clinical questions which were classified to 3 aspects,i.e.screening and diagnosis,treatment and long-term management of OSA.Conclusion·The quality of current global OSA guidelines varies a lot,and they need to be strengthened in terms of rigor of development,applicability,review and quality assurance,funding and conflict of interest declaration and management,especially those in Asia.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.