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 effects of G protein-coupled receptor 55 (GPR55) antagonist CID16020046 on renal fibrosis in mice, and provide a new method and idea for the treatment of renal fibrosis.Methods:(1) GPR55 overexpression and GPR55 antagonist CID16020046 were used in renal fibroblasts (NRK-49F) of rats, respectively. Meanwhile,transforming growth factor-β1 (TGF-β1) was applied in the NRK-49F cells to observe the expression of fibrosis-related factors and inflammatory factors. (2) A mouse model of renal fibrosis with unilateral ureteral obstruction (UUO) was established in vivo. Eight-week-old male C57BL/6J mice (20-25 g) were randomly divided into three groups according to the random number table method: sham group ( n=6), model group (UUO group, n=7), model + CID16020046 drug (UUO+CID group, n=8). The drug CID16020046 (10 mg/kg) was intraperitoneally injected 1 day before modeling, on the day of modeling and every day after surgery in UUO+CID group, and the corresponding dose of 0.9% normal saline was injected intraperitoneally in sham and UUO groups.The mice were sacrificed for sampling 7 days after UUO surgery, and their renal function indicators, liver transaminase, and cardiac markers were examined. Western blotting and quantitative real-time PCR were used to detect the expression of renal fibrosis-related factors and inflammatory factors. Immunohistochemistry staining, Sirius red staining and Masson trichrome staining were used to detect the pathological changes of renal tissues. Results:(1) After NRK-49F cells were stimulated by TGF-β1, the mRNA and protein expression levels of GPR55 were significantly increased (both P<0.05). There was no statistically significant difference in the mRNA expression of fibrosis-related factors fibronectin and collagen Ⅰ, and inflammatory factors interleukin-1β and tumor necrosis factor-α between TGF-β1 group and TGF-β1 + GPR55 overexpression group (all P>0.05). Compared with the TGF-β1 group, the protein expression levels of fibrosis-related factors alpha-smooth muscle actin (α-SMA) and vimentin, and the mRNA expression levels of collagen Ⅰ and α-SMA were lower in the TGF-β1 + CID group (all P<0.05). (2) Compared with sham group, the mRNA and protein expression levels of GPR55 in UUO group were higher (both P<0.05). The serum creatinine in the UUO+CID group was lower compared to the UUO group ( P<0.05). There was no statistically significant difference in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase isoenzyme between UUO group and UUO+CID group (all P>0.05). Compared with the UUO group, the protein expression levels of renal fibrosis-related factors fibronectin, collagen Ⅰ and vimentin, and the mRNA expression levels of fibronectin, collagen Ⅰ, collagen Ⅲ and α-SMA were lower in the UUO+CID group (all P<0.05). The degree of renal tubular dilation and interstitial collagen fiber deposition in the UUO+CID group was significantly reduced compared to the UUO group (all P<0.05). Conclusions:CID16020046 can reduce serum creatinine in UUO mice, protect renal function, and simultaneously decrease the expression of fibrosis-related factors in renal fibroblasts and mouse kidney tissues, thereby alleviating renal fibrosis.

Objective To explore the effect and mechanism of chemokine CX3CL1 on mouse liver fibrosis model.Methods C57BL/6 mice were randomly divided into CCl-4 model group and normal control group with 8 animals in each group.The model group was injected with 10%CCl-4 intra peritoneally for 6 weeks.After 6 weeks,the mice were sacrificed,and the pathological changes of the mouse liver were observed by HE staining.The level of CX3CL1 in peripheral blood of the mice was measured,and the expression level of CX3CL1 mRNA in the liver tis-sue of the mice was detected.In addition,in order to explore the mechanism of CX3CL1,the level of IFN-γ in mouse serum was detected as well.Results After the 6-week modeling,the liver pathology microscopy showed a successful modeling of liver fibrosis.The serum CX3CL1 level and liver tissue CX3CL1 expression in the model group were found to be significantly up-regulated,which suggested a potential impact on the pathogenesis of liver fi-brosis.In addition,the level of IFN-γ in the serum of mice in the model group increased significantly.Conclusions CX3CL1 is related to liver fibrosis in mice,and its mechanism might be explained by promoting the production of IFN-γ so to prevent liver fibrosis.

OBJECTIVE: To investigate the value of T2 mapping in the assessment of myocardial changes and prognosis in patients with acute ST segment elevation myocardial infarction (STEMI). METHODS: A retrospective study was conducted. A total of 30 patients with acute STEMI admitted to Tianjin First Central Hospital from January 2021 to March 2022 were enrolled as the experimental group. At the same time, 30 age- and sex-matched healthy volunteers and outpatients with non-specific chest pain with no abnormalities in cardiac magnetic resonance (CMR) examination were selected as the control group. CMR was performed within 2 weeks after the diagnosis of STEMI, as the initial reference. A plain CMR review was performed 6 months later (chronic myocardial infarction, CMI). Plain scanning includes film sequence (CINE), T2 weighted short tau inversion recovery (T2-STIR), native-T1 mapping, and T2 mapping. Enhanced scanning includes first-pass perfusion, late gadolinium enhancement (LGE), and post-contrast T1 mapping. Quantitative myocardial parameters were compared between the two groups, before and after STEMI myocardial infarction. The receiver operator characteristic curve (ROC curve) was used to evaluate the diagnostic efficacy of native-T1 before myocardial contrast enhancement and T2 values in differentiating STEMI and CMI after 6 months. RESULTS: There were no statistically significant differences in age, gender, heart rate and body mass index (BMI) between the two groups, which were comparable. The native-T1 value, T2 value and extracellular volume (ECV) were significantly higher than those in the control group [native-T1 value (ms): 1 434.5±165.3 vs. 1 237.0±102.5, T2 value (ms): 48.3±15.6 vs. 21.8±13.1, ECV: (39.6±13.8)% vs. (22.8±5.0)%, all P < 0.05]. In the experimental group, 12 patients were re-examined by plain CMR scan 6 months later. After 6 months, the high signal intensity on T2-STIR was still visible, but the range was smaller than that in the acute phase, and the native-T1 and T2 values were significantly lower than those in the acute phase [native-T1 value (ms): 1 271.0±26.9 vs. 1 434.5±165.3, T2 value (ms): 34.2±11.2 vs. 48.3±15.6, both P < 0.05]. ROC curve analysis showed that the area under the ROC curve (AUC) of native-T1 and T2 values in differentiating acute STEMI from CMI was 0.71 and 0.80, respectively. When native-T1 cut-off value was 1 316.0 ms, the specificity was 100% and the sensitivity was 53.3%; when T2 cut-off value was 46.7 ms, the specificity was 100% and the sensitivity was 73.8%. CONCLUSIONS The T2 mapping is a non-invasive method for the diagnosis of myocardial changes in patients with acute STEMI myocardial infarction, and can be used to to evaluate the clinical prognosis of patients.
Humans ; ST Elevation Myocardial Infarction/diagnosis* ; Contrast Media ; Prognosis ; Retrospective Studies ; Magnetic Resonance Imaging, Cine/methods* ; Gadolinium ; Myocardium/pathology* ; Myocardial Infarction ; Predictive Value of Tests

Background: The emergence of the severe acute respiratory syndrome coronavirus 2 omicron variant has been triggering the new wave of coronavirus disease 2019 (COVID-19) globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after diagnosis) of omicron infected patients are still unknown. Methods: Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19. The chest computed tomography (CT) images and clinical data obtained at baseline (at the time of the first CT image that showed abnormalities after diagnosis) and 1 month after diagnosis were longitudinally analyzed. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at baseline and residual pulmonary abnormalities after 1 month. Results: We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at baseline and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21 × 10 -9 /L, interleukin-6 (IL-6) ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at baseline. The age ≥ 47 years, presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up. For residual abnormalities group, the patients with less consolidations and more parenchymal bands at baseline could progress on CT score after 1 month. There were no significant changes in the number of involved lung lobes and total CT score during the early convalescent stage. Conclusion The higher IL-6 level was a common independent risk factor for CT abnormalities at baseline and residual pulmonary abnormalities at 1-month follow-up. There were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.

Objective:To explore the diagnostic performance of cardiac magnetic resonance imaging (CMR) with T1 mapping and T2 mapping for detection of acute phase of ischemic cardiomyopathy.Methods:Twenty-four patients with acute myocardial infarction (AMI) detected by coronary angiography from May 2020 to April 2021 in Tianjin First Center Hospital were selected. All patients underwent CMR (Philips Ingenia 3.0-T) at (9±4) days after definite diagnosis, which was defined as the first diagnosis. After 3 months and 6 months of chronic myocardial infarction (CMI) phase, one CMR was performed. On the same period with age and sex matching, a total of 26 cases of healthy volunteers and outpatient with non-specific chest pain and CMR examination without abnormality as control group. Plain scan included Cine, T2-weighted (STIR), and native T1/T2 mapping. The enhanced scan included perfusion, late gadolinium enhancement, post-T1 mapping. The changes of myocardial quantitative parameters before and after myocardial infarction were compared. Receiver operator characteristic curves (ROC curve) were developed to evaluate, compare, and distinguish the changes in the AMI group and the CMI group after 6 months.Results:Pre-enhanced T1 value, T2 value and extracellular volume (ECV) of AMI group were significantly higher than those of control group [pre-enhanced T1 value (ms): 1 438.7±173.4 vs. 1 269.2±42.3, pre-enhanced T2 value (ms): 49.8±9.3 vs. 21.7±4.0 , ECV (%): 33.2±10.2 vs. 27.2±2.1, all P < 0.05]. ECV was significantly higher in AMI (%: 33.2±10.2 vs. 27.2±2.1), but stabilized after 3 months (%: 33.2±10.2 vs. 32.4±5.1), and after 6 months later (%: 27.7±4.9 vs. 32.4±5.1), there were no significant difference (all P > 0.05). Pre-enhanced T1 and T2 values were significantly higher in AMI, lower after 3 months, but significantly decreased after 6 months [pre-enhanced T1 values (ms): 1 438.7±173.4 vs. 1 272.1±25.2, pre-enhanced T2 values (ms): 49.8±9.3 vs. 29.0±4.0, all P < 0.05]. The ROC curve showed that the specificity of pre-enhanced T1 and T2 values between AMI and CMI were 100%, and the sensitivity were 72.7%, 100%, respectively, pre-enhanced T1 and T2 value could be better distinguish between AMI and CMI diagnosis method. Conclusion:T1 mapping and T2 mapping with ECV can clearly diagnosis ischemic cardiomyopathy, especially pre-enhanced myocardial T1 and T2 values which is non-invasive diagnosis method of AMI, and can distinguish AMI or CMI, has a great significance to the patient's clinical treatment and follow-up.

Objective To summarize the computed tomographic (CT) manifestations of pulmonary aspergillosis after organ transplantation and compare different signs between pulmonary aspergillosis and bacterial pneumonia.Methods CT images of pulmonary aspergillosis (n =62) and bacterial pneumonia (n =68) in post-transplantation patients were reviewed.The signs were categorized with consolidation,mass,large nodule (≥1crn),small nodule and bud-in-tree pattern.Some detailed useful differentiating signs such as halo sign,air bronchogram sign,reversed halo sign,hypodensity sign and cavitation were also analyzed.Results CT patterns of pulmonary aspergillosis included consolidation,mass,large nodule,small nodule and bud-in-tree pattern.The most common was large nodule (75.8％),followed by consolidation (48.4％)and mass (29.0％).And small nodule (16.1 ％) and bud-in-tree (12.9％) patterns were concurrent.For consolidation pattern,the proportion of bacterial pneumonia (69.1％) was the larger;For mass pattern,the proportion of pulmonary aspergillosis (29.0％) was the larger.For large nodule pattern,there was no difference.The detail sign of large nodule in two groups had no difference In detailed signs of consolidation pattern,air bronchogram sign was more often seen in bacterial pneumonia while cavitation was more frequently found in pulmonary aspergillosis.In detailed signs of mass pattern,pulmonary aspergillosis often has single lesion (66.7％),cavitation (83.3％)and air crescent sign (77.8％) is more common.The proportion of halo sign was 30.7％.Conclusions CT manifestations of pulmonary aspergillosis are diverse after organ transplantation.There is some difference and yet overlap with bacterial pneumonia.

OBJECTIVE: To explore the effect of reactive oxygen species(ROS) and cell cycle in bone marrow cells in benzene-induced aplastic anemia(AA) mouse model. METHODS: Specific pathogens free male CD1 mice were randomly divided into control group and exposure group(n=10, each group). The mice in exposure group were subcutaneously injected with benzene at a dose of 2 mL/kg body weigh diluted 1 ∶1 in corn oil, while the mice in control group were treated with equal volume of corn oil, 3 times a week for a total of 25 times. After exposure, the blood routine and reticulocyte percentage of peripheral blood of mice were examined. The femur histopathology was performed. The levels of benzene and its metabolites hydroquinone, and phenol in blood, liver and bone marrow were tested by solid-phase extraction gas chromatography mass spectrometry. The level of ROS and the changes of cell cycle in bone marrow mononuclear cells(BMMNCs) were determined by flow cytometry. The protein expression of Cyclin D1 and cyclin-dependent kinase 4(CDK4) in BMMNCs was detected by Western blot. RESULTS: Since the 10 th benzene exposure, the body mass of mice in the exposure group was lower than that in the control group at the same time point(P<0.05). After the benzene exposure, all the counts of white blood cell, red blood cell, platelet, and hemoglobin level and reticulocyte percentage in peripheral blood of mice in the exposure group were decreased when compared with the control group(P<0.05). Bone marrow histopathological examination showed that bone marrow hematopoietic cells were decreased and non-hematopoietic cells were increased in the exposure group. In this study, a mouse model of AA induced by benzene was successfully established. The levels of benzene, hydroquinone and phenol in exposure group increased in blood, liver, and bone marrow compared to control group(P<0.05). Furthermore, the level of benzene from high to low were blood, liver and bone marrow, while the levels of hydroquinone and phenol were mainly stored in the blood and bone marrow in exposure group. Compared with the control group, the level of ROS, S phase fraction, and the relative protein expression of Cyclin D1 and CDK4 in BMMNCs increased, while the G1 phase fraction decreased in exposure group(P<0.01). CONCLUSION: The results suggest that benzene and its metabolites induce an increase of ROS level and S phase cell arrest, that play an important role in the pathogenesis and development of benzene-induced AA.

BACKGROUND: Chronic kidney disease is a severe threat to human health with no ideal treatment strategy. Mature mammalian kidneys have a fixed number of nephrons, and regeneration is difficult once they are damaged. For this reason, developing an efficient approach to achieve kidney regeneration is necessary. The technology of the combination of decellularized kidney scaffolds with stem cells has emerged as a new strategy; however, in previous studies, the differentiation of stem cells in decellularized scaffolds was insufficient for functional kidney regeneration, and many problems remain. METHODS: We used 0.5% sodium dodecyl sulfate (SDS) to produce rat kidney decellularized scaffolds, and induce adipose-derived stem cells (ADSCs) into intermediate mesoderm by adding Wnt agonist CHIR99021 and FGF9 in vitro. The characteristics of decellularized scaffolds and intermediate mesoderm induced from adipose–derived stem cells were identified. The scaffolds were recellularized with ADSCs and intermediate mesoderm cells through the renal artery and ureter. After cocultured for 10 days, cells adhesion and differentiation was evaluated. RESULTS: Intermediate mesoderm cells were successfully induced from ADSCs and identified by immunofluorescence and Western blotting assays (OSR1 + , PAX2 +). Immunofluorescence showed that intermediate mesoderm cells differentiated into tubular-like (E-CAD + , GATA3 +) and podocyte-like (WT1 +) cells with higher differentiation efficiency than ADSCs in the decellularized scaffolds. Comparatively, this phenomenon was not observed in induced intermediate mesoderm cells cultured in vitro. CONCLUSION: In this study, we demonstrated that intermediate mesoderm cells could be induced from ADSCs and that they could differentiate well after cocultured with decellularized scaffolds.
Animals ; Blotting, Western ; Fluorescent Antibody Technique ; Humans ; In Vitro Techniques ; Kidney ; Mesoderm ; Nephrons ; Rats ; Regeneration ; Renal Artery ; Renal Insufficiency, Chronic ; Sodium Dodecyl Sulfate ; Stem Cells ; Ureter