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 status of pain catastrophizing in patients with postherpetic neuralgia (PHN) and its influencing factors, and to analyze the correlation between pain catastrophizing and alexithymia. Methods A total of 243 PHN patients were recruited as study subjects and surveyed using a general information questionnaire, the Pain Catastrophizing Scale (PCS), and the 20-item Toronto Alexithymia Scale (TAS-20). Multiple linear regression analysis was conducted to explore the influencing factors of pain catastrophizing, and Pearson correlation analysis was used to explore the correlation between pain catastrophizing and alexithymia. Results The mean PCS score of the 243 PHN patients was (30.04±11.33), with the highest mean score for items in the helplessness dimension and the lowest for items in the magnification dimension. Multiple linear regression analysis showed that age, monthly family income per capita, disease duration, and pain intensity were independent influencing factors of pain catastrophizing in PHN patients (P < 0.05), collectively explaining 49.5% of the variance. Pearson correlation analysis showed a significant positive correlation between pain catastrophizing and alexithymia in PHN patients (P < 0.01). Conclusion PHN patients exhibit high levels of pain catastrophizing, which is influenced by age, disease duration, pain intensity, and monthly family income per capita. Furthermore, there is a significant positive correlation between pain catastrophizing and alexithymia.

Objective To explore the value of non-contrast CT findings of acute ischemic stroke(AIS)for predicting early prognosis after mechanical thrombectomy.Methods Data of 161 AIS patients from clinical center 1 who underwent mechanical thrombectomy were retrospectively analyzed.The patients were divided into training set(n=113)and internal test set(n=48)at the ratio of 7∶3,while 79 AIS patients who underwent mechanical thrombectomy from clinical center 2 were retrospectively enrolled as external test set.According to the National Institutes of Health stroke scale(NIHSS)scores 7 days after thrombectomy,patients'prognosis were classified as good(＜15 points)or poor(≥15 points).Pre-treatment non-contrast CT images of patients were reviewed,and CT findings were comparatively analyzed.Independent predictors of patients'early prognosis after mechanical thrombectomy were obtained with sequential univariate and multivariate logistic regressions,and a predicting model was established and visualized as a nomogram.The receiver operating characteristic curve was drawn,and the distinction was assessed with the area under the curve(AUC),then calibration was assessed with Hosmer-Lemeshow goodness of fit test,and the net benefit was evaluated with decision curve analysis(DCA).Results Alberta stroke program early CT score(ASPECTS),hyperdense middle cerebral artery sign(HMCAS)and basal ganglia calcification were all independent predictors of early prognosis of AIS after mechanical thrombectomy(all P＜0.05).The predictive model was established combining the above 3 variables and then visualized as a nomogram to predict prognosis of AIS after mechanical thrombectomy,with AUC of 0.776 in internal test set(χ2=6.052,P=0.417)and 0.800 in external test set(χ2=2.269,P=0.811).DCA showed that the nomogram might provide clinical net benefit within certain threshold probability ranges.Conclusion ASPECTS,HMCAS and basal ganglia calcification were all independent predictors of early prognosis of AIS after mechanical thrombectomy.The nomogram originated from predicting model combining the three could be used to somewhat accurately predict poor early prognosis after mechanical thrombectomy.

Objective To investigate associations between three-dimensional(3D)morphology of cervical vertebrae and skeletal mat-uration by cone-beam computed tomography(CBCT)and establish corresponding regression models for quantitatively evaluating cervical vertebral maturation(CVM).Methods The analyzed sample consisted of 358 CBCT images(175 male,183 female),of which 277 images were randomly selected as the model development group and 81 as the performance test group.Twenty-one 3D morphological pa-rameters were defined and measured,incorporating all parts of the cervical vertebrae,including the cervical vertebral bodies,transverse processes,spinous processes,pedicles,lamina,and articular processes.The cervical vertebral maturation index(CVMI)was determined by experienced orthodontists as reference standard.Spearman's rank correlation coefficient and multivariable stepwise regression analysis were used to identify the associations and build regression models.The performance test group was employed to ex-amine each model's reliability.Paired-samples Wilcoxon signed-rank test compared the CVMI of the model prediction with the reference standard.Results Three-dimensional morphological changes in various parts of the cervical vertebrae correlated with CVMI(P＜0.05).Six 3D morphometric parameters were each recognized for male and female models,three of which were identical.The adjusted R2 was 0.899 for males and 0.902 for females,with corresponding accuracies of 85.0%and 85.4%,respectively.These models showed no difference as compared with the reference standard(P＞0.05).Con-clusion New associations were found between 3D morphology of cer-vical vertebrae and skeletal maturation.The 3D-driven morphometric CVM assessment method and corresponding regression models exhibited good credibility and high consistency with experts.

【Objective】 To explore the mutation type, clinical characteristics, molecular genetics and the two-hit type of a patient with familial Von Hippel Lindau (VHL) syndrome. 【Methods】 The data of the patient were collected. DNA was extracted from the peripheral blood and renal cell carcinoma sample. The VHL gene germline mutation site was detected with high throughput sequencing next generation sequencing (NGS). The two-hit site was identified with UCSCXena database, methylation-specific PCR (MSP) and microsatellite stability detection. 【Results】 The mutation site of the embryo line was located in c.500G>A R167Q mutation. The patient had single nucleotide polymorphism, but no clear loss of heterozygosity, methylation or system mutation. 【Conclusion】 The germline mutation in exon 3 is the basis for the clinical features of this familial renal cell carcinoma proband. The identification of the two-hit site is key to the occurrence of the disease, which is significant for the diagnosis and treatment. The use of the databases can guide the screening of mutations and methylation sites in familial renal cell carcinoma.

Objective:According lung adenocarcinoma(LUAD)ferroptosis and non-coding RNA in patients with a long-chain(lncRNA)correlation,binding immunophenotyping constructing new risk rating model to assess the prognosis of LUAD patients.Methods:Based on bioinformatics technology,download the transcriptome data and clinical data of LUAD samples from the TCGA database,obtain genes related to ferroptosis from the FreeDb database,and used"caret"package to screen 504 cases of LUAD samples and randomly divided into training set and validation set according to the ratios of 50%and 50%.Pearson correlation analysis and univariate-factor Cox regression were used to screen ferroptosis-related lncRNA related to the prognosis of LUAD,and the"Conen-susClusterPlus"package of R software was used.Immune correlation analysis with CIBERSORT software,LASSO regression analysis to establish ferroptosis-related lncRNA model,receiver operating characteristic(ROC)curve and area under the curve(AUC)to test the performance of the prognostic model,and verified by validation set.Results:Univariate factor Cox and LASSO regression analysis constructed nine risk scoring models composed of lncRNA related to ferroptosis.Both univariate and multivariate Cox regression analy-sis showed that this prognostic model can be used as an independent prognostic factor(P<0.001).The model had good prediction performance in training set,internal validation set and external validation set.Conclusion:The risk score model of LUAD patients constructed in this study can be used as a new independent prognostic evaluation method,or it may have further application value.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the endoscopic modality of choice for the treatment of biliary and pancreatic diseases. However, patients with cirrhosis, particularly those with decompensated cirrhosis, are believed to be at increased risk for complications associated with ERCP. There is a paucity of literature describing the outcomes of ERCP for patients with cirrhosis. This study aimed to investigate the outcomes of ERCP for cirrhosis patients, especially adverse events, and evaluated its safety and efficacy. METHODS: We performed a multicenter, retrospective study of all patients at Beijing Friendship Hospital affiliated to Capital Medical University, Xijing Hospital affiliated to Air Force Military Medical University, Beijing Youan Hospital affiliated to Capital Medical University, and the Fifth Medical Center of the People's Liberation Army General Hospital from June 2003 to August 2019. The adverse events of inpatient ERCP for patients with ( n  = 182) and without liver cirrhosis (controls; n  = 385) were compared. RESULTS: A total of 567 patients underwent ERCP between January 2003 and December 2019 were enrolled in this study. Compared to patients without cirrhosis, patients with cirrhosis were at higher risk for postoperative complications (odds ratio [OR], 4.172; 95% confidence interval [CI], 1.232-7.031; P  < 0.001) such as postoperative pancreatitis (OR, 2.026; 95% CI, 1.002-4.378; P  = 0.001) and cholangitis (OR, 3.903; 95% CI, 1.001-10.038; P  = 0.036). The main indications for ERCP for patients with cirrhosis in this study included choledocholithiasis (101 cases; 55.5%), benign bile duct strictures (46 cases; 25.3%), and malignant bile duct strictures (28 cases; 15.4%). Among them, 23 patients (12.6%) underwent balloon dilation and 79 patients (43.4%) underwent sphincterotomy. Of the patients with cirrhosis, delayed bleeding occurred in ten patients (5.5%), postoperative pancreatitis occurred in 80 patients (44.0%), and postoperative cholangitis occurred in 25 patients (13.7%). An additional multivariate analysis showed that the total bilirubin (TBIL) level (OR, 4.58; 95% CI, 2.37-6.70) and Child-Pugh score of C (OR, 3.11; 95% CI, 1.04-5.37) were risk factors for postoperative complications in patients with cirrhosis. CONCLUSIONS Compared with the general population of patients undergoing ERCP, patients with cirrhosis were more prone to postoperative pancreatitis and cholangitis. TBIL levels and Child-Pugh scores were risk factors for postoperative complications in patients with cirrhosis.
Humans ; Cholangiopancreatography, Endoscopic Retrograde/adverse effects* ; Retrospective Studies ; Constriction, Pathologic ; Risk Factors ; Liver Cirrhosis/complications* ; Pancreatitis/etiology* ; Postoperative Complications/epidemiology* ; Cholangitis

Objective To externally validate the accuracy of combined use of neutrophil-lymphocyte ratio (NLR),V20,and Dmean in predicting the incidence of grade Ⅲ or higher radiation-induced lung injury (RILI) in lung cancer patients.Methods A total of 166 lung cancer patients,who participated in the model establishment were selected into the internal validation group,and 85 lung cancer patients who received intensity-modulated radiotherapy in our department between June 2016 and June 2018 were assigned into the external validation group.The incidence rate of grade 3 or higher RILI was statistically compared between the internal and external validation groups.Multivariate logistic analysis was performed for NLR,V20 and Dmean The discrimination degree of the predictive model was evaluated by using ROC curve in combination with NLR,V20 and Dmean The calibration degree of the predictive model was assessed by Hosmer-Lemeshow test.Results The incidence rate of grade 3 or higher RILI in the internal and external validation groups was 23.8％ and 22.9％.Multivariate logistic analysis demonstrated that NLR,V20 and Dmean significantly differed in the internal validation group (P=0.032,0.006 and 0.005).However,only V20 significantly differed in the external validation group (P=0.038).The discrimination and calibration degree of RILI was almost consistent between the internal and external validation groups (both P＞0.05).The area under the curve (AUC) predicted by NLR,V20,Dmean and the combination of three indexes were 0.611,0.646,0.682 and 0.775 in the internal validation group,and 0.544,0.702,0.658 and 0.754 in the external validation group,respectively.The calibration degree in the internal validation group was P=2.797and 0.834,P=2.452 and 0.653 in the external validation group.Conclusion Combined application of NLR,V20 and Dmean can accurately predict the incidence of grade Ⅲ or higher RILI in lung can cancer patients,which has been validated by external dataset.

Objective To assess the influence and early diagnosis treatment of bronchiectasis using severity score in patients with chronic obstructive pulmonary disease (COPD) combined with bronchiectasis. Methods Sixty patients with bronchiectasis in stable stage were selected from July 2016 to August 2017. The patients were divided into simple bronchiectasis group (32 cases) and bronchiectasis combined with COPD group (28 cases). The general clinical features, chest high-resolution CT (HRCT), pulmonary function, fractional exhaled nitric oxide (FENO) and bronchiectasis severity score between 2 groups were compared. The changes of the indexes 6 months after treatment with inhaled salmeterol fluticasone (50 μg/250 μg) in bronchiectasis combined with COPD group were observed. Results The bronchiectasis severity score and FENO in bronchiectasis combined with COPD group were significantly higher than those in simple bronchiectasis group: (4.82 ± 0.91) scores vs. (2.88 ± 0.83) scores and (39.04 ± 9.57) nmol/L vs. (28.66 ± 6.12) nmol/L, and there were statistical differences (P＜0.01). The forced expired volume in one second as a percentage of expected value (FEV1% Pred) and forced vital capacity as a percentage of expected value (FVC%Pred) in bronchiectasis combined with COPD group were significantly lower than those in simple bronchiectasis group: (61.36 ± 5.23)% vs. (71.28 ± 6.67)% and (61.57 ± 7.60)% vs. (72.84 ± 7.19)% , and there were statistical differences (P＜0.01). In bronchiectasis combined with COPD group, there were statistical differences in the bronchiectasis severity score, FEV1% Pred, FVC% Pred and FENO 6 months after treatment with inhaled salmeterol fluticasone and before treatment (P＜0.05). There was a negative correlation between FEV1% Pred and bronchiectasis severity score before and after treatment (r＝-0.802 and-0.618, P＜0.05); and there was a positive correlation between the FENO and bronchiectasis severity score (r ＝ 0.728 and 0.586, P＜0.05). Conclusions The pathogenetic condition of bronchiectasis combined with COPD is severe compared with simple bronchiectasis. Inhaled salmeterol fluticasone is effective in patients with bronchiectasis combined with COPD.

Objective Compared with chest CT,endoscopic ultrasonography (EUS) can more accurately determine the upper and lower margins of esophageal cancer,and marking the upper and lower margins of the esophageal cancer with titanium clip contributes to the delineation of target area of esophageal cancer during radiotherapy.To compare the effects of esophageal X-ray,chest computed tomography (CT)scan and EUS-assisted placement of marker clip in the determination of the length of gross target volume (GTV),aiming to provide reference for the determination of GTV during esophageal cancer radiotherapy.Methods Thirty patients who were initially diagnosed with thoracic esophageal cancer by histological and cytological examinations and scheduled to receive radiotherapy were recruited in this investigation.All patients received esophageal X-ray,CT scan,and EUS-assisted placement of marker clip.The length of GTV was quantitatively measured and statistically compared among three different methods.Results The length of GTV was (6.1 ± 1.4) cm,(6.8± 1.9) cm and (6.3± 1.9) cm determined by esophageal X-ray,CT scan and EUS-assisted placement of marker clip,respectively.Compared with CT scan,the length of GTV determined by EUS-assisted placement of marker clip did not significantly differ (P=0.11).The length of GTV determined by esophageal X-ray was significantly shorter than that by CT scan (P =0.03).Among all patients,the length of GTV determined by EUS-assisted placement of marker clip was longer compared with that by chest CT scan in 22.2％ of patients.The length of GTV determined by EUS-assisted placement of marker clip was the same as that by chest CT scan in 11.1％ of patients.The length of GTV determined by EUS-assisted placement of marker clip was shorter compared with that by chest CT scan in 66.7％ of patients.Conclusions EUS-assisted placement of marker clip differs from esophageal X-ray and CT scan in determining the length of GTV,which acts as one of the effective methods in the determination of the length of GTV during esophageal cancer radiotherapy.