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 CT diagnosis and differential diagnosis of perivascular epithelioid cell neoplasms (PEComa), improve the accuracy of PEComa diagnosis, and reduce misdiagnosis. Methods CT findings of 8 cases of PEComa confirmed by pathology in Jining First People’s Hospital from January 2020 to April 2024 were retrospectively analyzed for the location, shape, size, boundary, plain scan density, and enhancement characteristics of the lesions. Results All 8 tumors were solitary, with 5 located in the kidney, 1 in the liver, 1 in the extraperitoneal space, and 1 in the retroperitoneal space. The tumors were round in 3 cases, oval in 1 case, and irregular in 4 cases. Seven cases were benign with clear boundaries and 1 case was malignant with unclear boundaries. On plain CT, 2 cases showed slightly low density, 3 cases showed slightly high density, and 3 cases showed low density. One tumor had uniform density, and 7 tumors had nonuniform density with internal necrosis and cystic changes. Contrast-enhanced CT revealed diverse enhancement patterns. Four cases showed a “fast in and fast out” enhancement pattern, with significant arterial-phase enhancement and reduced portal venous-phase enhancement. Three cases showed a “fast-in and slow-out” enhancement pattern, with significant enhancement in the arterial phase, persistent enhancement in the portal venous phase, and slightly reduced density in the delayed phase. One case showed mild enhancement in the arterial phase and significant enhancement in the portal venous phase. In 3 cases, multiple tortuous and thickened blood vessels were observed around the tumors, while 3 cases showed tortuous vascular shadows within the tumors. Conclusion PEComa demonstrates characteristic CT features, predominantly with “fast in and fast out” or “fast in and slow out” enhancement patterns. When thickened and tortuous blood vessels are observed within or around the tumor, PEComa should be considered in combination with clinical findings.

Objective To evaluate the effectiveness of screening-intervention management program for high risk population of stroke in community.Methods Participants aged≥60 years old in Tairi Community,Fengxian District,Shanghai from May 2019 to July 2022 were selected as screening and intervention objects.The first round of stroke high-risk group screening was conducted in 2019 and 2020 in two years respectively,and the second round of stroke high-risk group screening(re-screening)was conducted in 2021 and 2022 respectively for the 2019 and 2020 screening groups,and the groups who had received stroke high-risk screening in both rounds of screening(overlapping groups)were selected as the observation objects of this study.The cerebrovascular function score was used to screen the high-risk individuals of stroke,75-100 was classified as non-high-risk,＜75 were classified as high risk,among which 50-74,25-49,0-24 were light,medium and severe risk,in turn.Baseline and follow-up data were collected for all screening groups,including systolic blood pressure,diastolic blood pressure,overweight or obesity,fasting blood glucose,glycated hemoglobin,triglyceride,total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,and blood uric acid.After the completion of screening,the test report interpretation and first diagnosis intervention were carried out on the screening site,and the screening results were recorded into the health examination file.The first intervention includes lifestyle intervention,risk factor intervention and therapeutic intervention for high-risk individuals.Lifestyle intervention and risk factor intervention were conducted through the distribution of popular science handbook for stroke prevention and individualized face-to-face guidance.Therapeutic intervention for high-risk individuals was guided by anti-platelet aggregation drug therapy,statin therapy,and further examination and treatment of cerebral vessels according to stroke risk assessment results and the incidence of related chronic diseases.Prior to the implementation of the project,the incidence of stroke in the community in 2018 was retrospectively investigated to compare annual changes in stroke screening-intervention.In the process of implementation of intervention management,stroke incidence monitoring of the whole community registered population was carried out,and the monitoring method was to conduct stroke incidence registration once a year,and cooperate with the disease control and community police station to obtain the community stroke incidence monitoring data and death registration information provided by the police station from 2018 to 2022.Results A total of 5 188 subjects who completed both the initial screening and the follow-up screening and met the inclusion and exclusion criteria were identified,of whom 2 269 were male and 2 923 were female.The age of participants ranged from 60 to 93 years at the time of the first round of screening,with a mean age of(68±6)years.The proportions of subjects in the age groups of 60-64,65-69,70-74,and≥75 years were 30.3％,34.7％,21.1％,and 14.0％,respectively.(1)After screening and intervention,the proportion of individuals with increased systolic blood pressure,diastolic blood pressure,fasting blood glucose,triglyceride,and low-density lipoprotein cholesterol all decreased(respectively 49.4％vs.57.3％,26.6％vs.28.7％,9.6％vs.10.9％,14.7％vs.17.0％,2.4％vs.3.3％;all P＜0.05),but the proportion of individuals with hyperuricemia increased(15.8％vs.13.1％,P＜0.01),with statistically significant differences.(2)Before the implementation of the screening-intervention program in 2018,the stroke incidence rate in the community was 332.1/100 000.The stroke incidence rates in the community during the period from 2019 to 2022 after the implementation of the screening-intervention program were 335.0/100 000,270.8/100 000,235.0/100 000,and 193.6/100 000,respectively.The incidence rates of ischemic stroke(x2trend=8.350,P=0.004)and stroke(x2trend=9.910,P=0.002)decreased during the period from 2019 to 2022,while the incidence rate of hemorrhagic stroke did not show a decreasing trend(x2trend=1.636,P=0.201).(3)The median baseline and follow-up cerebrovascular function scores for the 5 188 elderly individuals undergoing residual stroke risk screening were 82.50(52.50,98.75)and 88.5(59.00,100.00),respectively,with stroke risk rates of 39.8％and 35.6％before and after intervention,respectively.After intervention,the follow-up cerebrovascular function scores increased compared to the baseline,and the stroke risk rate decreased.The distribution of stroke risk levels before and after screening-intervention had statistically significant differences(P＜0.01).Conclusion Implementing a stroke high-risk population screening-intervention management program for the elderly in the community,combined with health examinations and family doctor team services,can significantly reduce the incidence,high-risk rate,and exposure level of risk factors for stroke in the community.

Objectives:To explore the value of improving the sensitivity of Epstein-Barr virus(EBV) DNA detection for the diagnosis and efficacy assessment of nasopharyngeal carcinoma.Methods:This was an observational study. The precision of the EBV DNA detection system used in this study was verified at the level of 100 copies/ml in accordance with the requirements of verification experiments, and the accuracy of the detection system was evaluated by comparing with digital PCR method. Totally 52 plasma samples were collected from patients who were newly diagnosed with undifferentiated non-keratinizing carcinoma of the nasopharynx at Nanfang Hospital of Southern Medical University from December 2021 to May 2022 in addition to156 plasma samples from nasopharyngeal carcinoma patients treated at the Radiotherapy Department of the hospital, and a retrospective analysis was also performed on 5 488 plasma samples that had been submitted for quantitative EBV DNA detection over the same period at the hospital. The effetcs of raising the EBV DNA detection threshold from 500 copies/ml to 100 copies/ml on the detection rate of nasopharyngeal carcinoma and the therapeutic efficacy assessment were compared.Results:The bias between the logarithmic values of the detected quantities and the target quantities was below±0.4 ( CV=6.94%) for the testings of 30 repetitions of the sample at the level of 100 copies/ml. The circulating EBV DNA of 156 patients with nasopharyngeal carcinoma was measured by the detection system and by digital PCR, and the results of the two methods showed good consistency ( r=0.95, P<0.001). By raising the EBV DNA detection threshold from 500 copies/ml to 100 copies/ml, the detection rate of nasopharyngeal carcinoma in untreated patients increased from 67.31% (35/52) to 82.69% (43/52). For nasopharyngeal carcinoma patients under treatment, the peripheral blood EBV DNA detection rates were 12.82% (20/156) and 23.72% (37/156) with detection thresholds of 500 copies/ml and 100 copies/ml, respectively. Conclusion:This research improved the EBV detection rate by increasing the sensitivity of EBV DNA assays, which is of great significance for the auxiliary diagnosis and therapeutic efficacy assessment in nasopharyngeal carcinoma patients.

Objective:To study the experience and efficacy of treating the isolated left vertebral artery (ILVA) during total aortic arch replacement combined with stent-trunk surgery in patients with Stanford type A aortic dissection (TAAD) combined with ILVA.Methods:The clinical data of 21 patients with TAAD combined with ILVA from July 2017 to March 2022 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. All patients were treated with ILVA-left common carotid artery transplantation and total arch replacement combined with stent-trunk surgery under moderate hypothermia cardiopulmonary bypass and selective cerebral perfusion (SCP). Among them, aortic root repair surgery was in 15 cases, Bentall surgery in 6 cases, coronary artery bypass grafting performed simultaneously in 2 cases. The surgical details, postoperative complications and length of stay were recorded. The patients were followed up 1 and 12 months after surgery for CTA examination to observe the patency of transplanted ILVA. The follow-up was performed until October 1, 2022, and survival, aorta-related death and ILVA patency rate were recorded.Results:Three hundred and thirty-five TAAD patients were admitted during the same period, including 21 (6.27%) with ILVA. ILVA was reconstructed successfully in all patients. No complications related to ILVA were observed. Three cases died during the perioperative period: 1 case had preoperative myocardial infarction due to coronary artery involvement and the CPB could not be removed after operation; 1 case died of postoperative liver and renal failure due to severe organ hypoperfusion; 1 case suffered from postoperative acute renal failure and died of low cardiac output. The patients did not experience damage to the vagus nerve or recurrent laryngeal nerve, lymphatic leakage, chylothorax, ILVA thrombosis, paraplegia or cerebral vascular complications. The other 18 patients recovered and discharged from hospital. The median duration of follow-up was 30 (6 to 62) months. During the follow-up, aortic-related death did not observe, ILVA was unobstructed, and there were no manifestations of anastomotic stenosis or arterial stenosis.Conclusions:ILVA is a supra-aortic trunk variant, it is not so rare. ILVA may pose additional difficulties during total arch replacement surgery. The clinical effect of prior reconstruction of ILVA by ILVA-LCCA transposition is satisfactory, and it may be a simple and efficient method to complete reconstruction and optimize arch surgery before cardiopulmonary bypass.

Rheumatoid arthritis （RA）， as an autoimmune disease， is mainly characterized by persistent synovitis. It often involves multiple joints symmetrically and can lead to joint deformity， joint function loss， and even disability in severe cases. The pathogenesis of RA is complex， and the prevention and treatment are complicated. Therefore， it is difficult to cure the disease completely. Previous studies have validated important targets and mechanisms for the prevention and treatment of RA， including the nuclear factor-κB （NF-κB） signaling pathway that controls the inflammatory process， nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway that regulates oxidative stress， inhibits inflammation， and maintains cell homeostasis， Wnt/β-catenin signaling pathway that plays a key role in cell growth， differentiation， apoptosis， and inflammatory response， anti-inflammatory， anti-oxidation， and silent information regulator 1 （SIRT1） signaling pathway that regulates synovial cells， anti-inflammatory adenylate-activated protein kinase （AMPK） signaling pathway that regulates energy metabolism， and hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway related to angiogenesis in RA. At the same time， many studies have confirmed that traditional Chinese medicine prevents and treats RA by regulating the above signaling pathways and exerting their related effects， indicating the advantages of traditional Chinese medicine such as multiple regulatory pathways， long-term effects， and less adverse reactions. In this paper， by consulting many research reports， the role of the above-mentioned signaling pathways in RA was clarified， and the latest research results of traditional Chinese medicine intervention in the above-mentioned signaling pathways in the prevention and treatment of RA in recent years were summarized in detail. This paper aims to promote the in-depth study of the pathogenesis of RA and its treatment with traditional Chinese medicine， provide a scientific basis for the rational application of traditional Chinese medicine， and offer useful enlightenment for the development of new drugs and clinical practice for the treatment of RA in the future.

BACKGROUND:There is no consensus on the optimal bone tunnel position in the lateral clavicle,which guides coracoclavicular ligament reconstruction.Postoperative complications such as enlargement of the lateral clavicle bone tunnel,bone osteolysis,clavicle fracture,and failure of internal fixation are likely to occur.Bone mass density plays an important role in the strength and stability of endophytic fixation.Regional differences in the bone mass density of the distal clavicle should not be overlooked in the repair and reconstruction of acromioclavicular dislocation.Currently,there are no quantitative clinical studies in humans regarding the bone mass density of the distal clavicle. OBJECTIVE:To measure the magnitude of bone mass density in different regions of the distal clavicle by quantitative CT to provide a reference for surgeons to repair and reconstruct the coracoclavicular ligament. METHODS:101 patients undergoing quantitative CT checking in Fuyang People's Hospital Affiliated to Anhui Medical University from October to December 2022 were enrolled,from which 1 616 samples of subdivisional bone mass density of the distal clavicle were measured.For each of the quantitative CT samples,firstly,the distal clavicle was divided medially to laterally into the following four regions:conical nodal region(region A),inter-nodal region(region B),oblique crest region(region C)and distal clavicular region(region D).Secondly,each region was divided into the first half and the second half to determine eight subdivisions,then setting semiautomatic region of interest(ROI)in each subdivision:(ROI A1,A2,B1,B2,C1,C2,D1,and D2).Thirdly,each quantitative CT scan was transferred to the quantitative CT pro analysis workstation,and cancellous bone mass density was measured in the distal clavicle ROI.Finally,the clavicular cortex was avoided when measuring. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in bone mineral density on the different sides of the shoulder(P＞0.05).(2)The analysis of bone mineral density in eight sub-areas of the distal clavicle A1,A2,B1,B2,C1,C2,D1,and D2 showed statistically significant differences(P＜0.05).It could be considered that there were differences in bone mineral density in different areas of the distal clavicle.After pairwise comparison,there was no statistically significant difference in bone mineral density between A1 and A2,D1 and D2,A2 and B1(P＞0.05),and there was a statistically significant difference in bone mineral density between the other sub-areas(P＜0.05).(3)The bone mineral density in the region A2 of the anatomical insertion of the conical ligament was significantly higher than that in the inter-nodular area(region B)(P＜0.05).The bone mineral density in the region A1 was higher than that in the region A2,but the difference was not statistically significant(P＞0.05).The bone mineral density in the region C1 of the anatomical insertion of the trapezium ligament was higher than that in regions C2,D1 and D2,and the bone mineral density in the inter-nodular area(region B)was significantly higher than that in regions C and D(P＜0.05).(4)These results have suggested that there are differences in bone mass density in different regions of the distal clavicle;regional differences in bone mass density in the distal clavicle during repair and reconstruction of acromioclavicular dislocation cannot be ignored.Consideration should be given not only to biomechanical factors but also to the placement of implants or bone tunnels in regions of higher bone mass density,which could improve the strength and stability of implant fixation and reduce the risk of complications such as bone tunnel enlargement,osteolysis,fracture and implant failure.

Objective To analyze the perioperative outcomes of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection. Methods The perioperative clinical data of patients receiving heart valve replacement in the Department of Cardiovascular Surgery, the First Affiliated Hospital of University of Science and Technology of China from November 2022 to February 2023 were retrospectively analyzed. According to whether the patients were infected with SARS-CoV-2, they were divided into a non-infected group and an asymptomatic group. The perioperative data of the patients were compared between the two groups, and the effect of asymptomatic infection on the result of heart valve replacement surgery was analyzed. Results A total of 66 patients were enrolled including 36 males and 30 females with a mean age of 58.0±11.1 years. There were 51 patients in the non-infected group and 15 patients in the asymtomatic group. There were 2 patients of mitral valve replacement, 20 patients of aortic valve replacement, 1 patient of double valve replacement, 3 patients of aortic valve replacement with tricuspid valvoplasty, 22 patients of mitral valve replacement and tricuspid valvoplasty, 18 patients of double valve replacement and tricuspid valvoplasty. Asymptomatic infected patients received more emergency surgery than uninfected patients (26.7% vs. 0.0%, P<0.01). There was no statistical difference in the duration of extracorporeal circulation, aortic occlusion, mechanical ventilation time after the surgery, ICU stay, postoperative drainage volume, or postoperative complications between the two groups. Conclusion Perioperative results of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection and non-infection are almost the same.

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.

Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.