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 analyze the risk factors associated with the occurrence of rectal neuroendocrine tumors (RNETs) and construct a risk prediction model. Methods Clinical data of patients who underwent electronic colonoscopy were collected. The clinical information on patients with and without RNETs were compared, and potential risk factors for RNETs were identified. Binary logistic regression was performed to analyze the relevant risk factors and construct a risk prediction model. Results Among 164 patients, 66 were diagnosed with RNETs, and 98 who did not have such a condition were randomly selected. Univariate logistic regression analysis revealed that age, fatty liver, anxiety and depression, total cholesterol, triglyceride levels, and carcinoembryonic antigen (CEA) were significant factors influencing the occurrence of RNETs (P<0.05). Multivariate logistic regression analysis identified age (P=0.015), anxiety and depression (P=0.031), cholesterol level (P=0.009), fatty liver (P=0.001), and CEA (P<0.001) as independent risk factors for RNETs. The participants were randomly divided into training and test sets at a 7:3 ratio. The training set was used to construct a nomogram-based risk prediction model, and the testing set was used for internal validation. The area under the curve values for the training and testing sets were 0.843 and 0.772, respectively (P>0.05). These findings indicate a good discriminative performance. The calibration curves for the training and testing sets were in good agreement with the 45° standard line, which suggests that the predicted probabilities were consistent with the actual outcomes. Decision curve analysis showed that the model provided a high net benefit within a threshold range of 0.2 to 0.7 for clinical decision making. Conclusion Young age, fatty liver, high CEA levels, high cholesterol levels, and anxiety and depression are independent risk factors for RNETs. The nomogram model constructed based on these risk factors exhibits a strong capability to predict the occurrence of RNETs, and clinical intervention can be considered based on the predicted probability values.

Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, possesses various biomedical activities and has garnered significant attention because of its notable anticancer properties. This article reviews the research progress on the antitumor mechanisms of EGCG, focusing on its roles in inducing tumor cell apoptosis; inhibiting tumor cell proliferation, angiogenesis, invasion and metastasis; modulating the tumor microenvironment; and influencing epigenetic modifications. Given its natural origin, safety, and low cost, EGCG could be a preferred option for the development of new cancer therapeutic drugs or enhancing the efficacy of combination therapies. This work aims to provide a theoretical foundation for further research and development of EGCG and scientific evidence for its application in cancer prevention and treatment.

ObjectiveTo investigate the preventive and therapeutic effects of Tiaogan Huaxian pills combined with entecavir on hepatic fibrosis in chronic hepatitis B with liver Qi stagnation， spleen deficiency， and blood stasis syndrome and its effect on diffusion-weighted imaging （DWI）. MethodClinical data of 117 patients with liver disease who visited the Department of Hepatology at the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2021 to April 2022 were retrospectively analyzed. According to different treatment plans， they were divided into a control group （59 cases） and a treatment group （58 cases）. Both groups of patients received entecavir-based etiology treatment， and the treatment group added Tiaogan Huaxian pills on the basis of basic treatment. Both groups were treated for 24 weeks. Before and after treatment， the two groups were compared in terms of alanine aminotransferase （ALT）， advanced surgical technologies （AST）， total bilirubin （TBil）， hepatitis B virus （HBV）-DNA conversion rate， liver stiffness measurement （LSM）， four items of liver fibrosis （hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， and laminin）， the fibrosis index based on four factors （FIB-4）， the aspartate aminotransferase to platelet ratio index （APRI）， the apparent diffusion coefficient （ADC） value in magnetic resonance imaging （MRI）， and traditional Chinese medicine symptom scores， so as to analyze the efficacy of the two groups. ResultBefore treatment， there was no significant difference in ALT， AST， TBil， LSM， four items of liver fibrosis， FIB-4， APRI， HBV-DNA conversion rate， ADC value， and traditional Chinese medicine symptom scores between the two groups. After treatment， both groups of patients showed significant reductions in ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， and APRI （P<0.05） and a significant increase in ADC value （P<0.05） and HBV-DNA conversion rate （P<0.01）. The traditional Chinese medicine symptom score of the treatment group decreased significantly （P<0.05）. Compared with the control group after treatment， the effective rate of clinical traditional Chinese medicine in the treatment group was 91.38% （53/58）， which was significantly higher than that of the control group （54.23%， 32/59） （Z=-4.325， P<0.01）. In the treatment group， ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， APRI， and traditional Chinese medicine symptom scores all decreased significantly （P<0.05）， and the increase in ADC values was more significant （P<0.05）， while the difference in HBV-DNA conversion rate was not statistically significant. There were no serious adverse reactions or events in either group. ConclusionTiaogan Huaxian pills combined with entecavir have significant clinical efficacy in the treatment of hepatic fibrosis in chronic hepatitis B， which can reduce liver inflammation activity， delay hepatic fibrosis progression， and reduce traditional Chinese medicine symptom scores. It is worthy of clinical promotion and application.

Objective To investigate the role of microRNA(miR)-567 in the proliferation,migration and cell cycle of non-small cell lung cancer(NSCLC)through regulation of cyclin dependent kinase 8(CDK8)and its clinical relevance.Methods Tumor tissues and adjacent tissues of 40 NSCLC patients were collected,and the expressions of miR-567 and CDK8 were detected by real-time quantitative fluorescent PCR(qRT-PCR).miR-NC mimic,miR-567 mimic,oe-NC,and oe-CDK8 were transfected into A549 and H1975 cells.The ex-pressions of miR-567 and CDK8 were detected using qRT-PCR.Cell proliferation was detected by CCK-8 method,and cell migration was detected by Transwell assay.Cell cycle changes were detected by flow cytome-try.The targeting of miR-567 and CDK8 was detected by luciferase reporter gene assay.Results In the tumor tissues of NSCLC patients,the expression of miR-567 was decreased,while the expression of CDK8 was in-creased,and the two were negatively correlated(P＜0.05).In A549 and H1975 cells,miR-567 mimic group was compared with miR-NC mimic group,the expression of miR-567 was increased,the expression of CDK8 was decreased,the proliferation and migration levels of cells were decreased,the proportion of G1 phase was increased,and the proportion of S phase was decreased.The fluorescence intensity of miR-567 mimic group was lower than that of miR-NC mimic group in normal CDK8.miR-567 mimic+oe-CDK8 group was compared with miR-567 mimic+oe-NC group,the expression of CDK8 was increased,the proliferation and migration levels of cells were increased,the proportion of cells in G1 phase was decreased,and the proportion of cells in S phase was increased.Conclusion miR-567 can inhibit NSCLC proliferation and migration by targeting CDK8 expression and controlling tumor cell arrest in the S phase.

Objective:To investigate the application effect of case-based learning (CBL) based on the clinical case library of stomatology in standardized residency training for comprehensive stomatology.Methods:A total of 52 residents in Department of Stomatology, Chongqing Medical University, were given CBL teaching based on the clinical case library of comprehensive stomatology, and a questionnaire survey was performed to evaluate the teaching effect. Theoretical and skill assessments were performed before and after CBL teaching, and a comparative analysis was performed. SPSS 19.0 software was used for the t-test. Results:The questionnaire survey showed that CBL teaching based on the clinical case library of stomatology effectively improved the ability of independent learning [92.31% (48/52)], the interest in learning [88.46% (46/52)], and the ability for case diagnosis and the accuracy of investigation and judgment [94.23% (49/52)]. This method helped with the mastery and understanding of the theoretical knowledge in stomatology [96.15% (50/52)] and improved the abilities for expression and communication [84.62% (44/52)] and the ability to find and solve problems [94.23% (49/52)]. It also helped to stimulate the interest in scientific research and teaching [82.69% (43/52)] and create an active classroom atmosphere [82.69% (43/52)]. Among these residents, 94.23% (49/52) liked CBL teaching, and 88.64% (46/52) thought the setting of the case library was reasonable. After the application of CBL teaching, there were significant increases in theoretical score [from (66.74±4.25) points to (81.44±7.16) points] and skill examination score [from (64.00±3.14) points to (81.96±7.50) points].Conclusions:CBL teaching based on the case library of stomatology has a good teaching effect in the standardized residency training for comprehensive stomatology and can not only improve the theoretical and skill assessments of residents, but also improve their learning interest and clinical thinking ability.

Objective To analyze the detection of helicobacter pylori(Hp)in different parts of gastric antrum,and to provide clinical guidance for finding the best biopsy site for Hp.Methods Patients who underwent 13C urea breath test and electronic gastroscopy from January 2020 to December 2022 were retrospectively analyzed and divided into 13C urea breath test positive group[delta over baseline(DOB)≥4]and 13C urea breath test negative group(DOB<4)according to DOB value.Gastroscopy reports and pathological data of patients were collected.According to different biopsy sites in gastric antrum,patients were divided into conventional biopsy site group,elevated erosive site group and flat erosive site group,and the detection rate of Hp in different biopsy sites was compared.13C urea breath test positive group was divided into group A(435)according to DOB value,and the gastric antral biopsy and pathology of each group were classified and analyzed.Combined with endoscopic reports and pathological data,patients were divided into atrophic gastritis group and non-atrophic gastritis group.Results In the 13C urea breath test positive group,the detection rate of Hp in the elevated erosive site group(96.4%)was higher than that in the conventional biopsy site group(92.7%)and the flat erosive site group(93.9%),and the difference was statistically significant(P = 0.036).In DOB group A,the detection rate of Hp was the highest at the site of elevated erosive and the lowest at the site of conventional biopsy,and the detection rate of Hp at the three biopsy sites was compared,the difference was statistically significant(P = 0.016);There was no significant difference in the detection rate of Hp at three biopsy sites between group B and group C(P = 0.622;P = 0.721);the non-atrophic gastritis group,the detection rate of Hp at the elevated erosive site(96.5%)was higher than that at the conventional biopsy site(91.2%)and the flat erosive site(92.0%),and the difference was statistically significant(P = 0.043).There was no significant difference in the detection rate of Hp at three biopsy sites in the atrophic gastritis group(P = 0.614).13C urea breath test negative group:There was no significant difference in Hp detection rate among the three biopsy sites(P = 0.255).Conclusion For patients with positive 13C urea breath test but low DOB value,the positive rate of Hp in the elevated erosive site is higher.For non-atrophic gastritis patients,the detection rate of Hp was higher in the elevated erosive sites than in the conventional biopsy sites.But for patients with atrophic gastritis,there was little difference in the detection rate of Hp in different parts of antrum.For patients with negative 13C urea breath test,there was no significant difference in Hp detection rate among the three biopsy sites.In future clinical work,for similar patients,precise biopsy can be performed to improve the detection rate of Hp.

Objective:To investigate the influencing factors of increased tube bleeding within 24 h after coronary artery bypass grafting(CABG) and its correlation with perioperative complications.Methods:This study was a prospective observational study. The patients with CABG surgery were enrolled in Beijing Anzhen Hospital affiliated to Capital Medical University from May 2018 to December 2021. The age, sex, complications, blood tests and other clinical data of outpatients were collected. Left ventricular ejection fraction(EF) and left ventricular enddiastolic diameter(LVED) were detected by echocardiography. MGF and PI of grafts were recorded during CABG. Perioperative troponin Ⅰ, blood clotting pentathlon, all-cause death, perioperative myocardial fraction, atrial fibrillation and stroke were collected. According to the tube bleeding within 24 h after operation, the patients were divided into increased group(tube bleeding>1 000 ml) and normal group(tube bleeding≤1 000 ml). The preoperative baseline data, intraoperative indexes and perioperative complications were compared between the two groups. Logistic regression, Spearman and linear regression models were used to analyze the correlation between tube bleeding within 24 h and clinical data.Results:304 patients underwent CABG were enrolled. There were 185 cases(60.9%) in the increased group and 119 cases(39.1%) in the normal group. After adjusting for age, sex and BMI, multivariate logistic regression analysis showed that male( OR=2.40, 95% CI: 1.38-4.18, P=0.002), history of stroke( OR=2.37, 95% CI: 1.07-5.26, P=0.034), and history of myocardial infarction( OR=1.81, 95% CI: 1.13-2.91, P=0.014) could significantly increase the risk of tube bleeding within 24 h after surgery. The average blood flow of the anterior descending branch( OR=0.99, 95% CI: 0.99-1.00, P=0.022) and the circumflex branch( OR=0.99, 95% CI: 0.98-1.00, P=0.003) during the operation was significantly negatively correlated with the increase of tube bleeding within 24 h after surgery, while the PI of anterior descending branch( OR=1.81, 95% CI: 1.26-2.61, P=0.001), circumflex branch( OR=1.45, 95% CI: 1.07-1.97, P=0.017), right coronary artery( OR=1.84, 95% CI: 1.29-2.62, P=0.001) were positively correlated with the increase of tube bleeding within 24 h after operation. In addition, prothrombin time significantly increased the risk of increased tube bleeding within 24 h after surgery( OR=1.16, 95% CI: 1.03-1.30, P=0.018). Linear regression analysis showed that there was a significant positive linear correlation between ICU time and tube bleeding within 24 h after surgery( OR=0.17, 95% CI: 0.96-4.58, P=0.003), and a significant negative linear correlation between postoperative ejection fraction and tube bleeding within 24 h( OR=-0.25, 95% CI: -33.18--13.07, P<0.001). Conclusion:Increased tube bleeding within 24 h after CABG is most common in males and patients with a history of cardiovascular and cerebrovascular infarction. Better graft hemodynamic parameters can reduce the tube bleeding within 24 h after the operation, further improve cardiac function and reduce ICU time.

OBJECTIVE To investigate the effect of nasal microflora on nasal function after endoscopic surgery in patients with chronic sinusitis and nasal polyps.METHODS There were 88 patients with chronic sinusitis with nasal polyps who underwent elective nasal endoscopic surgery in Daxing District People's Hospital from May 2021 to May 2022.High-throughput sequencing technology was used to analyze the distribution of microflora in nasal secretions,and the patients were divided into a microbial-negative group(24 cases),a bacteria-positive group(42 cases)and a fungus-positive group(22 cases).Visual analog scale,Lund-Kennedy endoscopic score and Lund-Mackay CT were used to evaluate the nasal function of the patients before and 6 months after surgery,respectively.After surgery,nasal endoscopy was used to evaluate the degree of nasal mucosal injury and the thickness of the basement membrane of the nasal mucosal tissue was measured.RESULTS There were 64 pathogens who were detected in nasal secretions of 88 patients with chronic sinusitis and nasal polyps,accounting for 47.73%of bacteria and 25.00%of fungi.After operation,the nasal function score of the three groups was significantly lower than that before operation,and the pair-to-pair comparison between the three groups had statistical significance(P<0.05).The damage degree and basement membrane thickness of nasal mucosal epithelium in bacteria positive group and fungi positive group were higher than those in microbial negative group(P<0.05),but there was no difference between groups(P>0.05).CONCLUSION Bacteria and fungi in nasal secretions can affect the recovery of nasal function after endoscopic surgery in patients with chronic sinusitis and nasal polyps,and affect the effect of endoscopic surgery.

ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang （XXMT） combined with electroacupuncture （EA） collaboratively in alleviating cerebral ischemia/reperfusion （I/R） injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling， rats in the XXMT+EA groups were administered XXMT at low （15 g·kg^-1）， medium （30 g·kg^-1）， and high （60 g·kg^-1） doses， alongside daily 20-min EA treatment （stimulating acupoints GV14 and GV20）. Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score， TTC staining， and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 （NLRP3）， Gasdermin D （GSDMD）， cysteinyl aspartate specific proteinase-1 （Caspase-1）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in the ischemic area of the cerebral cortex. ResultCompared with the sham group， the I/R group showed a significant increase in neurological deficit scores and infarct volume （P<0.01）， along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. In contrast， the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume （P<0.01）， and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway， thereby reducing neurological deficits， minimizing brain infarct size， and improving cortical neuronal damage.