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.

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.

This study was aimed at analyzing the effectiveness of vector control efforts at the 19th Asian Games in Hang-zhou,to provide a reference for future vector control at similar large-scale events.We collected and analyzed vector organism monitoring data for various venues at Asian Games(branch)villages and designated reception hotels(hotels and guesthouses)associated with the Asian Games in Hangzhou from April to October of 2023.Excel 2019 software and SPSS 20.0 software were used to organize the data.Paired t tests(for normally distributed data)or Wilcoxon signed rank tests(for data not nor-mally distributed)were performed,and count data were analyzed statistically with x2 tests.The larva mosquito path index at Asian Games venues peaked in June and then declined month by month.The first circle area of the adult mosquito human trapping index peaked in June,and the second circle area peaked in July.The mosquito indicators reached the corre-sponding control standards before the Asian Games.Moreo-ver,the differences in mosquito density before and after the Asian Games were statistically significant(all P＜0.05).Both the positivity rate and density of flies in rooms reached level A in the first and second circle areas from April to October.The proportion of indoor fly-proof facilities meeting the standards was lowest in May,then gradually increased.The corresponding control standards were reached in the first round in the fourth week of September,and in the second round in the first week of October.The difference in the density of positivity for room flies before and after the Asian Games was statistically significant(all P＜0.05).Rodent density reached the corre-sponding control standards in the second week of September.The proportion of anti-rodent facilities meeting the standards was lowest in June,and then gradually increased.The first round began to meet the corresponding control standards in the fourth week of September,and the second round began to meet the corresponding control standards in the first week of October.Ex-cept for the outdoor rat density path index,which was statistically significant before and after the Asian Games,the other indi-cators showed no statistical significance(P＞0.05).The cockroach density in the first circle area reached level A in all months,and that in the second circle area reached level B in mid-August.Vector control in the Hangzhou Asian Games achieved the ex-pected results,with no vector infringement or local vector-borne infectious diseases occurring.In future vector control for large-scale events,vector density monitoring should be performed as early as possible,and comprehensive prevention and control measures should be taken to maintain low vector density and prevent vector infringement incidents.

It is the focus of higher education reform in the new era to comprehensively promote the con-struction of ideology and political education based on the characteristics of professional courses and en-hancing the effectiveness of ideology and political education.As an important basic course for medical students in colleges,molecular biology is closely related to basic medical disciplines and clinical medi-cine,and is a rapidly developing cutting-edge discipline,which has the natural advantage of serving as a carrier of ideology and political education.In this study,the innovative integration of project-based group study (PBGS) with the outcome-oriented behavior (OBE) of moral education is applied to the teaching of the ideology and politics of the medical molecular biology course,and the integration of the two has made a useful exploration to enhance the effectiveness of the ideology and politics teaching of the course.Taking students as the center,we have constructed an ideology and politics teaching system for medical molecular biology courses by combining on-line and off-line teaching activities through improving the teaching objectives,innovating the teaching design,digging into the case of ideology and politics,intro-ducing a variety of teaching methods,strengthening the management of teaching practice,and optimizing the evaluation mode.After two years of teaching practice,this model has effectively improved the teach-ing effect of the medical molecular biology course.The academic performance of the students in the prac-tice group has improved significantly,and the teachers and students have been given excellent evalua-tion.The results of the questionnaires before and after class showed that more than 80％ of the students believed that their horizons had been broadened and their knowledge had been increased through learn-ing.More than 50％ of the students believed that their learning ability and innovation consciousness had been improved;their scientific research quality had been improved;and their confidence in studying medicine had been strengthened.By strengthening the cultivation of students' scientific research and in-novation capabilities,we guided students to participate in subject competitions and won many national a-wards.Throughout the teaching process,we aim to expand the breadth and depth of ideology and political education,cultivate scientific spirits,innovation ability,moral cultivation,and humanistic qualities.In sum,our work provides experiences for the cultivation of high-quality medical talents.

Objective:To explore the influence of environment temperature on the incidence of testicular torsion.Methods:We collected the clinical data on 172 cases of testicular torsion diagnosed in the Second Hospital of Hebei Medical University from De-cember 2013 to December 2020.According to the local environment temperature on the day of onset,we divided the patients into groups A(below 0℃),B(0-10℃),C(10-20℃)and D(above 20℃),and compared the incidence rates of testicular torsion among the four groups,followed by correlation analysis.Results:The incidence rate of testicular torsion was 12.8％(n=22)in group A,35.5％(n=61)in B,34.9％(n=60)in C and 16.9％(n=29)in D,the highest at 0-10℃ in group B,with sta-tistically significant difference among the four groups(x2=29.07,P＜0.001).Spearman correlation analysis indicated that the inci-dence of testicular torsion was negatively correlated with the environment temperature(r=-0.261,P＜0.01),with no statistically significant difference among different seasons(x2=5.349,P＞0.05),but higher in autumn and winter than in the other two sea-sons.Conclusion:The incidence of testicular torsion is negatively correlated with the environment temperature,elevated when the temperature decreases,but has no statistically significant difference among different seasons,though relatively higher in autumn and winter.

Objective:To assess the deformation of the bladder-neck opening and the impact of the bladder-neck angle(BNA)on urination in male patients by fluid-structure interaction(FSI)analysis.Methods:We established geometric models of the blad-der,prostate and urethra were established,incorporating both normal and enlarged BNAs,and assessed the effects of BNA alteration on urinary flow by FSI simulation of the flow rate and pressure of the urine within the bladder,bladder neck and urethra,and that of pros-tate displacement as well.We retrospectively analyzed the clinical data on 145 male patients from the Second Hospital of Hebei Medical University between June 2020 and June 2023,39 with acute urine retention(the AUR group)and 106 without(the non-AUR group),and evaluate the impact of BNA on urination based on the urinary flow rate and prostate volume.Results:Comparative simulation a-nalysis showed significant differences in the total urethral pressure and flow rate between the normal and enlarged BNA models(P＜0.05).The maximum prostate displacement was found at the bladder neck,with moderate displacement and unchanged urethral diame-ter in the normal BNA model,but significant displacement and a reduced urethral opening diameter in the enlarged BNA model.FSI analysis confirmed an evident impact of enlarged BNA on urination,more significant in the AUR than in the non-AUR patients(P＜0.05).The BNAs in the patients with the maximum urinary flow rate(Qmax)of＜10,10-15 or＞15 ml/s were 83.7°±2.5°,67.5°±1.8° and 65.1°±4.8° respectively,with statistically significant difference between the former one and the latter two groups(P＜0.05).The BNAs in the patients with normal prostate volume or BPH of grade Ⅰ,Ⅱ,Ⅲ or Ⅳ were 65.0°±3.7°,67.2°±3.1°,71.5°±2.0°,82.8°±3.5° and 105.8°±6.0°,respectively(P＜0.05),with statistically significant difference between BPH grades Ⅲ and Ⅳ(P＜0.05)as well as between these two and the other three groups(P＜0.05),but not among the normal prostate volume,BPH grade Ⅰ and BPH grade Ⅱ groups(P＞0.05).Spearman correlation analysis indicated that BNA was strongly correlated with total prostate volume(TPV),transition zone volume(TZV),intravesical prostatic protrusion(IPP),prostatic urethral angle(PUA),IPSS,and Qmax(P＜0.05).Conclusion:Changes in BNA affect urination and are closely associated with the se-verity of prostate hyperplasia.The BNA may be an important anatomical factor for assessing the severity of lower urinary tract symptoms in BPH patients.

AIM To study the chemical constituents form the leaves of Castanopsis orthacantha Fance and their α-glucosidase inhibitory activities.METHODS The methanol extract form the leaves of C.orthacanth was isolated and purified by various column chromatography methods,such as MCI gel CHP 20P,Sephadex LH-20,Diaion HP20SS,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The α-glucosidase inhibitory activities were determined by PNPG method.RESULTS Eighteen compounds were isolated and identified as protocatechuic acid(1),gallic acid(2),3-O-α-L-arabininopyranosyl-4-hydroxybenzoic acid(3),3-O-galloyl shikimic acid(4),methyl 4-epi-shikimate-3-O-gallate(5),5-O-galloyl shikimic acid(6),5-O-caffeoylshikimic acid(7),6-O-galloyl-glucoside(8),1,6-di-O-galloyl-β-D-pyranogluloside(9),1,3-di-O-galloyl-α-D-glucoside(10),2,3-di-O-galloyl-D-glucoside(11),β-O-methylgluco-2,3-digalloyl esters(12),(3R,1'S)-[1'-(6"-O-galloyl-β-D-gluco-pyranosyl)oxyethyl]-3-hydroxy-dihydrofuran-2(3H)-one(13),4-O-D-(6'-O-galloyl)glucopyranyl-(E)-p-coumaryl acid(14),chestanin(15),1-desgalloyl eugeniin(16),picrorhiza acid(17),11-methyl chebulate(18).The IC50 values of compounds 2 and 16 were(0.12±0.059),(0.00089±0.00025)mmol/L,respectively.CONCLUSION All compounds are isolated from the leaves of C.orthacantha for the first time.Compounds 2 and 16 have strong α-glucosidase inhibitory activities.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.