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.

The pursuit of cosmetic effects in post-surgical wounds has led to the development of ultra-minimally invasive techniques in surgery. Minimal invasive surgery has replaced open surgery and has become the new gold-standard for treating diseases. One such technique is the single incision triangulated umbilicus surgery (SITUS), which offers several advantages over traditional laparoscopic and other scarless surgeries, including reduced trauma, faster recovery, and better cosmetic outcomes. SITUS also has a short learning curve, aligns with conventional instrumentation operating habits, and can be used for whole abdominal surgeries. Chinese scholars have made further improvements to the SITUS technology, including expanding its applicability in intra-abdominal surgery and refining its incision closure methods to achieve superior cosmetic results. Currently, SITUS technology is experiencing rapid development in urology applications and has demonstrated satisfactory results in both domestic and international reports. This review aims to discuss the effectiveness and development of the SITUS technique in urology.

Objective:To explore the risk factors for 30-day death in emergency department patients, and then construct a prediction model and validate it using nomogram.Methods:A retrospective cohort study was conducted. The clinical data of 1 091 patients admitted to the emergency department of the First People's Hospital of Changde from January 1 to June 30, 2021 was collected, including 741 patients from January 1 to March 31 in the development group and 350 patients from April 1 to June 30 in the validation group. General information, first vital signs admitted to the emergency department, and laboratory results were collected, the modified early warning score (MEWS) was calculated, and 30-day outcomes were recorded. Univariate and multivariate Logistic regression analysis was used to screen out the risk factors of 30-day death. According to the results of multivariate analysis, the nomogram was used to construct a 30-day death prediction model. The receiver operator characteristic curve (ROC curve) was used to evaluate the consistency of the prediction model, the calibration of the prediction model was evaluated by the Hosmer-Lemeshow goodness of fit test.Results:A total of 1 091 patients were enrolled. There were 741 patients in the development group, including 356 males and 385 females, aged (51.42±17.33) years old, and the 30-day mortality was 28.88%. There were 350 patients in the validation group, including 188 males and 162 females, aged (52.88±16.11) years old, and the 30-day mortality was 24.00%. The results of the univariate analysis showed that age, primary diagnosis on admission, consciousness, respiratory rate (RR), systolic blood pressure (SBP), heart rate (HR), pulse oxygen saturation (SpO 2), MEWS score, erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and body mass index (BMI) might be the risk factors for 30-day death in patients in the emergency department. The results of the multivariate analysis showed that the MEWS score [odds ratio ( OR) = 14.22, 95% confidence interval (95% CI) was 1.46-138.12], ESR ( OR = 46.71, 95% CI was 20.48-106.53), PCT ( OR = 4.97, 95% CI was 2.46-10.02), BMI (24.0-27.9 kg/m 2: OR = 37.82, 95% CI was 14.69-97.36; ≥28.0 kg/m 2: OR = 62.11, 95% CI was 25.77-149.72) were independent risk factors for 30-day death in the emergency department (all P < 0.05). Using the four variables with the results of multivariate analysis to construct a nomogram prediction model, the area under the ROC curve (AUC) was 0.974 (95% CI was 0.753-0.983) for the development group, and the AUC was 0.963 (95% CI was 0.740-0.975) for the validation group. The Hosmer-Lemeshow test showed no statistically significant difference between the predicted outcome of the nomogram prediction model and the actual occurrence ( χ2 = 1.216, P = 1.270). Conclusion:The prediction model developed by the MEWS score combined with BMI, ESR and PCT can scientifically and effectively predict the 30-day outcome of emergency department patients.

Objective:To investigate the effect of iguratimod (IGU) on transforming growth factor-β 1 (TGF-β 1)-induced primary human lung fibroblasts (pHLFs) activation and collagen secretion. Methods:Mice pulmonary fibrosis (PF) models were established in vivo and were divided into three groups: the control group (CTR group), the Bleomycin (BLM) group and the BLM+IGU group, hematoxylin-eosin (HE) staining was used to observe lung morphology, and Masson staining was used to observe the degree of collagen accumulation in lung. Fibronectin and smooth muscle 22 (SM22) were detected by immunofluorescence, and the content of hydroxyproline in lung tissue was detected by chloramine-T method. In vitro, pHLFs were used to assess the effect of IGU on TGF-β 1 stimulation in four groups: CTR group, IGU group, TGF-β 1 group and TGF-β 1+IGU group, the apoptosis of cells was detected by flow cytometry, and the mRNA expression of collagen type Ⅰ (COL-Ⅰ) and collagen type Ⅲ (COL-Ⅲ) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of α-smooth muscle actin (α-SMA), fibronectin, p-Smad2, p-Smad3 and transcription coactivator p300 were detected by Western blot and immunofluorescence. One-way ANOVA was used for all data, and LSD- t test or Kruskal-Wallis test was used for pair comparison. Results:The content of hydroxyproline in CTR group, the BLM group and the BLM+IGU group was (0.552±0.075) μg/mg, (1.293±0.081) μg/mg and (0.833±0.053) μg/mg ( F=169.672, P<0.01) respectively. IGU reduced the content of hydroxyproline in the lung tissue of mice, reduced the accumulation of collagen in the lung, and thus reduced the degree of BLM-induced pulmonary fibrosis, and improved the pathological changes in the lung of mice. In cell experiments, IGU had no significant effect on apoptosis ( F=0.83, P=0.54). The relative expression levels of COL-Ⅰ mRNA in the CTR group, TGF-β 1 group and TGF-β 1+IGU group were (100.4±1.2), (299.0± 13.0) and (202.5±7.0) respectively ( F=468.7, P<0.01). The relative expression levels of COL-Ⅲ mRNA in the CTR group, TGF-β 1 group and TGF-β 1+IGU group were (99.8±1.9), (350.6±8.0) and (220.3±9.9) respectively ( F=468.7, P<0.01). The relative expression levels of α-SMA protein were (0.193±0.038) in CTR group, (0.530±0.061) in TGF-β 1 group, and (0.410±0.065) in TGF-β 1+IGU group ( F=35.620, P<0.01); The relative expression levels of fibronectin in CTR group, TGF-β 1 group, and TGF-β 1+IGU group were (0.200±0.020), (0.700±0.020) and (0.410±0.066) respectively ( F=123.326, P<0.01). The relative expression levels of p-Smad3 protein in CTR group, TGF-β 1 group, and TGF-β 1+IGU group were (0.120±0.020), (0.573±0.586) and (0.327±0.252) respectively( F=92.987, P<0.01); The relative expression levels of p300 in CTR group, TGF-β 1 group and TGF-β 1+IGU group were (0.180±0.055), (0.923±0.025) and (0.650±0.050) respectively ( F=207.676, P<0.01). IGU significantly decreased the mRNA expression levels of COL-Ⅰ and COL-Ⅲ induced by TGF-β 1, inhibited the protein expression levels of α-SMA, fibronectin, p300, and phosphorylation of Smad2/3. Conclusion:Our results revealed the beneficial effect of IGU on the inhibition of TGF-β 1-mediated pHLFs activation and collagen secretion via the Smad3/p300 pathway, thus suggest that it might act as an effective anti-fibrotic agent in preventing the progression of PF.

Objective:To investigate the clinical value of sevoflurane inhalation combined with epidural anesthesia in the operation of digestive tract malignant tumors in the elderly.Methods:From August 2016 to September 2017, 74 elderly patients with digestive tract malignant tumors who were operated in the Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou were divided into two groups by random number table method, with 37 cases in each group.The control group was given sevoflurane inhalation anesthesia, while the observation group was given sevoflurane inhalation combined with epidural anesthesia.The changes of blood pressure, heart rate and cognitive function were observed.Results:There were no statistically significant differences in blood pressure and heart rate between the two groups at 5 minutes after tracheal intubation (all P>0.05). After 0 and 10 min of recovery of bilateral lung ventilation, the blood pressures of the observation group were (74.75±4.93)mmHg, (72.79±4.60)mmHg, respectively, which were lower than those of the control group [(82.44±3.62)mmHg, (75.70±5.14)mmHg] ( t=7.648, 2.562, all P<0.05). The heart rate of recovery of bilateral pulmonary ventilation in the observation group was (70.75±4.21) times/min, which in the control group was (75.91±3.89)times/min, the difference was statistically significant between the two groups( t=5.476, P<0.05). The cognitive function scores of the observation group were (25.74±0.69)points, (26.13±1.49)points, (27.90±0.77)points, (28.26±1.18)points, respectively, which were higher than those of the control group [(19.88±2.30)points, (22.85±0.96)points, (24.38±1.21)points, (24.35±1.63)points] ( t=14.844, 11.256, 14.929, 11.819, all P<0.05). Conclusion:Sevoflurane inhalation combined with epidural anesthesia is effective for elderly patients with digestive tract malignant tumors, which can avoid excessive fluctuation of physical signs and promote the recovery of cognitive function.

BACKGROUND/AIMS: To investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomarkers for differentiating S0–S2 (early fibrosis) from S3–S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection. METHODS: One hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative polymerase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0–S2 from S3–S4. RESULTS: Serum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis progressed from S0–S2 to S3–S4 (p < 0.05), but not miR-16. The multivariate logistic regression analysis identified a panel of three miRNAs and platelets that were associated with a high diagnostic accuracy in discriminating S0–S2 from S3–S4, with an area under the curve of 0.936. CONCLUSIONS: The levels of the studied miRNAs, with the exception of miR-16, varied with fibrosis progression. A panel was identified that was capable of discriminating S0–S2 from S3–S4, indicating that serum miRNA levels could serve as a potential noninvasive biomarker of fibrosis progression.
Biomarkers ; Biopsy ; Early Diagnosis* ; Fibrosis ; Hepatitis B virus ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Liver Cirrhosis* ; Liver* ; Logistic Models ; MicroRNAs* ; Polymerase Chain Reaction ; ROC Curve

Objective To study interleukin-23 (IL-23) levels in serum and dendritic cells of acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B (CHB) and to explore its relationship with the prognosis.Methods Peripheral blood mononuclear cells and serum were collected from 40 ACLF patients with CHB (including survival group 27 cases and non-survival group 13 cases) and 26 healthy controls.Monocytes were induced to immature dendritic cell in vitro and TNF-α was added to induce dendritic cell maturation.IL-23 mRNA of dendritic cells was detected by real time polymerase chain reaction (PCR), and serum IL-23 level was measured by enzyme-linked immuno sorbent assay (ELISA).Differences among the parameters with normal distribution were compared using t test, those with non-normal distribution were compared using non-parametric Mann-Whitney U-test, and the relationship between two variables was assessed by Spearman′s rank correlation.Results International normalized rate (INR) and model for end-stage liver disense (MELD) scores in non-survival group of ACLF were higher than those in survival group (INR: 2.32 vs 1.64, U=69.00, P=0.002 2;MELD:36 vs 30, U=64.50, P=0.001 4).However, there were no significant differences between two groups at gender, age, alanin aminotransferase (ALT), aspartate aminotrans ferase (AST), bilirubin, creatinine, hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and serum IL-23.IL-23 mRNA level in dendritic cells at baseline in non-survival group of ACLF was significantly higher than that in survival group (76 vs 43, U=71.50, P=0.002 8).After treatment, serum IL-23 was significantly declined in survival group ([160±75] ng/L vs [91±49] ng/L, t=4.012, P=0.000 2), but not in non-survival group.Significant positive correlation was observed between IL-23 mRNA level in dendritic cells and MELD score at baseline (r=0.7198,P<0.01).Conclusions Persistent high serum IL-23 level suggests poor prognosis in ACLF patients with CHB.IL-23 mRNA expression in dendritic cells has good consistency with MELD score and the patients with high IL-23 mRNA expression has poor outcome.

Objective To systematically evaluate the efficacy,safety and recent curative effects of delta-shaped anastomosis in totally laparoscopic distal gastrectomy (ICBI) for gastric carcinoma.Methods Literatures in English and Chinese comparing ECBI and ICBI published up to November 2015 were searched from international and national online databases.Meta-analysis was conducted by Review Manager 5.3 soft ware.Results There are eleven studies involved,with 2020 gastric cancer patients,including,1 169 ECBI cases and 851 ICBI cases.Meta-analysis showed that there was no significant statistical differences between ECBI group and ICBI group in operative time,resection margin length,overall postoperative complications and anastomosis-related complications.(all P ＞ 0.05).When compared to ECBI,the estimated blood loss was significantly less in ICBI,and ICBI with more retrieved lymph nodes,faster recovery of gastrointestinal function,less use of painkiller and shorter postoperative hospital stay (all P ＜ 0.05).Conclusion ICBI is safe and feasible in treatment of gastric cancer,and has a good short-term effect.

OBJECTIVE To determine the genetic cause of a child with blepharophimosis, ptosis, and epicanthus inverses syndrome and tetralogy of Fallot, and to correlate the phenotype with the genotype. METHODS Routine G-banding has been previously performed on the patient and her parents. Chromosome microarray analysis (CMA) was performed for the three individuals and the fetus. RESULTS Chromosomal analysis has suggested normal karyotypes for the child and her parents. However, a de novo 8.9 Mb deletion on chromosome 3q22.1-q23 was detected by CMA. The deleted region has encompassed 74 genes including 41 disease-related genes, and this is also the most frequent region involved in interstitial 3q deletion. Patients with deletion of this region often have a common feature of dysplasia of eyelids, as well as a spectrum of other anomalies according to different breakpoints, including microcephaly, skeletal anomalies, congenital heart defects, cranial anomalies, intellectual disability and developmental delay. The patient's phenotype was in accordance with such spectrum. Her parents and sib did not show this variation by CMA. CONCLUSION The de novo interstitial deletion of 3q22.1-q23 probably underlies the main clinical manifestation in this child. CMA can provide more detailed information and allow further investigation of the genotype-phenotype correlation.
Blepharophimosis ; genetics ; Child, Preschool ; Chromosomes, Human, Pair 3 ; Female ; Humans ; Mitochondrial Proteins ; genetics ; Phenotype ; Ribosomal Proteins ; genetics ; Skin Abnormalities ; genetics ; Tetralogy of Fallot ; genetics ; Urogenital Abnormalities ; genetics

Objective To explore a novel and highly specific small-molecule TNFβinhibitor by using computer-aid?ed virtual screening and cell-based assays in vitro. Methods Computer-aided drug design and virtual screening were used to design and identify chemical compounds that targeted TNFβbased on the crystal structure of the TNFβ-TNFR1 com?plex. The effect of the small-molecule compound against TNFβ-induced cytotoxicity of L929 cells was detected by MTT as?say, and the efficacy of the compound to inhibit TNFβ-induced apoptosis of L929 cells was determined by flow cytometry as?say. The impact of the compound on L929 cell cycle was examined by Propidium Iodide (PI) staining and flow cytometry, and the influence of the compound on TNFβ-triggered signal pathway was analyzed by Western blot assay and Ultra VIEW VOX 3D Live Cell Imaging System. Results No.35 compound (named as C35 thereafter) could effectively inhibit TNFβ-induced cell death in a dose dependent manner, and the half-maximum inhibition concentration (IC50) was 8.19μmol/L. Furthermore, C35 had lower cytotoxicity and minimal effect on L929 proliferation. Here we further revealed that C35 could affect TNFβ-induced apoptotic pathway by blocking the activation of Caspase 3, and markedly reduce L929 cell apoptosis induced by TNFβ. Conclusion A novel TNFβsmall-molecule inhibitor was identified by combining computer-aided virtual screening with functional assays, and which could block TNFβ-triggered apoptotic pathway and efficiently inhibit the cell death in?duced by TNFβ.