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.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective To observe the effect of a Jianpi Huayu Jiedu formula on the NLRP3-mediated pyroptosis pathway in gastric precancerous lesion(GPL)associated with Helicobacter pylori(Hp)infection.Methods A GPL mouse model was prepared using Hp suspension gavage combined with Atp4a gene-deficient mice.The Jianpi Huayu Jiedu formula was administered as an intervention.Gastric mucosal tissue pathological damage was observed using hematoxylin and eosin(HE)staining.The presence of intestinal metaplasia(IM)was assessed using Alcian Blue-Periodic Acid Schiff(AB-PAS)staining.Ultrastructural changes in cell organelles were observed using transmission electron microscopy.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of gastrin-17(G-17),pepsinogen I(PGI),and proinflammatory cytokines IL-1β and IL-18.The expression of molecules related to the pyroptosis pathway was detected using Western blot and real-time quantitative PCR(RT-qPCR).Results Compared to the control group,Hp-related GPL mice exhibited gastric mucosal atrophy accompanied by IM and dysplasia.Damage to mitochondria and endoplasmic reticulum in parietal cells was observed.Levels of G-17,PGI,and proinflammatory cytokines IL-1β and IL-18 were elevated.The expression of molecules related to the pyroptosis pathway was increased.The Jianpi Huayu Jiedu formula significantly reduced gastric mucosal tissue pathological damage in GPL mice,decreased G-17 and PGI levels,mitigated inflammatory responses,and downregulated the expression of molecules related to the pyroptosis pathway.Conclusion The Jianpi Huayu Jiedu formula may exert its effects by inhibiting the NLRP3-mediated pyroptosis signaling pathway,thereby alleviating or even reversing the pathological damage of gastric mucosa in Hp-related GPL.

Berberine is a kind of isoquinoline alkaloid extracted from the roots and rhizomes of many medicinal plants,such as Coptis chinensis of Ranunculus family,Phellodendron chinensis of rutaceae family,and Berberine Sanacanthus family.In recent years,with the deepening of research,berberine has shown re-markable prevention and treatment effect in a variety of neuro-psychiatric disease models.This paper summarizes the research progress of berberine in neuropsychiatric diseases and provides theoretical support for further clinical prevention and treatment of neuropsychiatric diseases.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective To observe the effect of a Jianpi Huayu Jiedu formula on the NLRP3-mediated pyroptosis pathway in gastric precancerous lesion(GPL)associated with Helicobacter pylori(Hp)infection.Methods A GPL mouse model was prepared using Hp suspension gavage combined with Atp4a gene-deficient mice.The Jianpi Huayu Jiedu formula was administered as an intervention.Gastric mucosal tissue pathological damage was observed using hematoxylin and eosin(HE)staining.The presence of intestinal metaplasia(IM)was assessed using Alcian Blue-Periodic Acid Schiff(AB-PAS)staining.Ultrastructural changes in cell organelles were observed using transmission electron microscopy.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of gastrin-17(G-17),pepsinogen I(PGI),and proinflammatory cytokines IL-1β and IL-18.The expression of molecules related to the pyroptosis pathway was detected using Western blot and real-time quantitative PCR(RT-qPCR).Results Compared to the control group,Hp-related GPL mice exhibited gastric mucosal atrophy accompanied by IM and dysplasia.Damage to mitochondria and endoplasmic reticulum in parietal cells was observed.Levels of G-17,PGI,and proinflammatory cytokines IL-1β and IL-18 were elevated.The expression of molecules related to the pyroptosis pathway was increased.The Jianpi Huayu Jiedu formula significantly reduced gastric mucosal tissue pathological damage in GPL mice,decreased G-17 and PGI levels,mitigated inflammatory responses,and downregulated the expression of molecules related to the pyroptosis pathway.Conclusion The Jianpi Huayu Jiedu formula may exert its effects by inhibiting the NLRP3-mediated pyroptosis signaling pathway,thereby alleviating or even reversing the pathological damage of gastric mucosa in Hp-related GPL.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To explore the correlation between palm temperature,disease activity,and traditional chinese medicine syndrome types in patients with rheumatoid arthritis(RA).Methods:80 RA patients(RA group)who were admitted to our hospital from April 2022 to June 2024 were selected,they were divided into high group(DAS28 score＞5.1 score)and low to moderate group(2.6 score ≤ DAS28 score≤5.1 score)according to the 28 joint disease activity scores(DAS28).70 healthy volunteers who underwent physical examinations during the same period(control group)were selected.The palm temperature,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),and DAS28 scores between the control group and RA group were compared.The palm temperature,ESR,and CRP levels between low to moderate group and high group were compared.The correlation between palm temperature and disease activity,ESR,and CRP levels in RA patients was analyzed by Pearson correlation.The distribution of traditional chinese medicine syndrome types in RA patients was observed,the palm temperature,ESR,and CRP levels of RA patients with different traditional chinese medicine syndrome types were compared.Results:The palm temperature,ESR,CRP levels,and DAS28 score in the RA group were higher than those in the control group(P＜0.05).The palm temperature,ESR,and CRP levels in the high group were higher than those in the low to moderate group(P＜0.05).Pearson correlation analysis results showed that,the palm temperature of RA patients was positively correlated with DAS28 score,ESR,and CRP levels(P＜0.05).Among 80 RA patients,there were 17 cases(21.25％)of liver and kidney deficiency syndrome,23 cases(29.02％)of cold and dampness obstruction syndrome,14 cases(17.86％)of qi and blood deficiency syndrome,17 cases(21.47％)of damp heat obstruction syndrome,and 9 cases(11.52％)of phlegm and blood stasis obstruction syndrome.The palm temperature,ESR,and CRP levels of patients with Qi and blood deficiency syndrome,liver and kidney deficiency syndrome,and phlegm and blood stasis obstruction syndrome increased in sequence and were higher than those of patients with damp heat obstruction syndrome and cold and dampness obstruction syndrome(P＜0.05).There was no statistical difference in palm temperature,ESR,and CRP levels between the groups of damp heat obstruction syndrome and cold and dampness obstruction syndrome(P＞0.05).Conclusion:There is a certain correlation between the palm temperature and disease activity and traditional chinese medicine syndrome types of RA patients.Regular observation of palm temperature,ESR,CRP levels,and DAS28 score is helpful for assessing the condition of RA patients.