Study of synovial mesenchymal stem cells combined with PRP in cartilage repair / 中国医学装备

Objective:To compare the repair effects of three kinds of treatment methods included synovial mesenchymal stem cells(SMSCs),platelet rich plasma(PRP)and the combination of them with knee joint cavity injection on cartilage injury of rabbit.Methods:A total of 24 New Zealand rabbits were selected to establish a cartilage injury model of knee joint by using surgery in knee joint of them.The rabbits with cartilage injury model were divided into four groups using a random number table method,which included blank group,single SMSCs with joint cavity injection group(SMSCs group),PRP with joint cavity injection group(PRP group)and the combination of SMSCs and PRP with joint cavity injection group(SMSCs+PRP group),with 6 rabbits in each group.The synovium of four groups of rabbits were scraped off their joints to conduct in vitro culture of SMSCs,as well as the morphological observation and identification of SMSCs.The venous bloods of rabbits were extracted to prepare PRP by centrifugation.The contents of PRP,platelet and growth factor in blood were compared.The SMSCs and PRP were injected into the knee joint cavity of three groups of rabbits with model.After 2,4 and 6 weeks of injection treatment,the repair statuses of cartilages at defection area of different groups were evaluated according to cartilage repair scoring table of International Association for Cartilage Repair(ICRS).Results:The primary synovial cells of rabbit knee joint synovium were initially round in shape after isolation,but almost all of them were spindle shaped after passage.The positive detection rates of SMSCs surface antigen CD73,CD90 and CD105 of 4 group were respectively 100%,99.22%and 99.99%.The CD45 detection was 0.5%,which indicated that they possessed the property of stem cell.The platelet count of 4 groups showed that the platelet concentration in PRP was approximate 6 times of that in whole blood.The concentrations of platelet derived growth factor(PDGF),transforming growth factor-β(TGF-β)and vascular endothelial growth factor(VEGF)were respectively(569.15±57.48)ng/mL,(633.56±63.90)ng/mL and(1 243.55±106.04)ng/mL in PRP,which were approximately 5 times,6 times and 7 times of that in whole blood,respectively.After 2 weeks of injection treatment for joint cavity,there was no significant statistical difference in the scores of cartilage repair among 4 groups(P>0.05).At 4 and 6 weeks of injection treatment,the morphological and histological score of cartilage repair of the SMSCs+PRP group were significantly higher than those of the blank group,and the differences were significant(t4 week=6.35,9.15,t6 week=8.16,8.60,P<0.05),respectively.Conclusion:The repair effect of SMSCs combined with PRP on cartilage injury of rabbit is significantly better than that of single PRP and single SMSCs,respectively,and all of them are better than those without treatment.SMSCs combined with PRP can significantly improve the effect of self-repair of cartilage injury.

The comparative study on the extraction methods of exosomes from synovial fibroblasts in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective:To compare the efficiency and purity of exosomes extracted from synovial fibroblasts of patients with rheumatoid arthritis by ultracentrifugation, size exclusion chromatography and modified polymer precipitation.Methods:The exosomes were extracted from human synovial fibroblasts by ultracentrifugation, size exclusion chromatography and modified polymer precipitation. Transmission electron microscopy, particle size detection and western Blot were used to identify the morphological characteristics, particle size distribution, concentration, and expression of marker proteins. One-way analysis of variance (ANOVA) was used for comparison among the three groups, and LSD- t test was used for pairwise comparison. P<0.05 was considered statistically significant. Results:Exosomes could be successfully obtained with all three extraction methods. The typical "saucer-like" structure could be observed under transmission electron microscope. The marker proteins of exosomes TSG101, Syntenin-1 and CD63 were all detectable by western blot. The peaks of main particle size were located within 30~150 nm. As for purity, the exosomes obtained by ultracentrifugation showed the highest purity, while modified polymer precipitation was the worst, with a large number of polymer particles and impurities protein. The purity of exosomes obtained by size exclusion chromatography was the moderate. For extraction efficiency, concentrations of exosomes particles obtained by the three methods were different ( F=9.61, P=0.049), and modified polymer precipitation was significantly higher than ultracentrifugation in terms of concentration of exosomes particles [(98.0±17.0)×10 10 particles/ml vs (11.6±7.7)×10 10 particles/ml, t=-4.34, P=0.023]. Conclusion:Human synovial fibroblasts derived exosomes canbe obtained by three methods. Ultracentrifugation is time-consuming, but can produce high-purity exosomes, which may be considered in the situation when high purity requirement with large volume samples are needed. Size exclusion chromatography is a good choice with high yield and purity exosomes, and suitable for small volume samples. Modified polymer precipitation is not recommended due to production of lowest purity exosomes.

Development and validation of a nomogram diagnostic model for the diagnosis of Prosthetic Joint Infections based on serum and joint fluid inflammatory markers / 中华骨科杂志

Objective:To construct a column-line diagram diagnostic model based on serum and joint fluid inflammatory markers for the diagnosis of periprosthetic joint infections (PJI) after joint arthroplasty and to validate its predictive ability.Methods:The clinical data of 181 patients diagnosed with PJI or aseptic loosening in the Department of Orthopedics of the First Affiliated Hospital of Chongqing Medical University from January 2015 to June 2020 were retrospectively collected as a modeling group. The best indicators for diagnosing PJI were screened by lasso regression, single-factor and multifactor analysis. By comprehensively considering the weights and intrinsic connections of the indicators, a column-line diagram diagnostic model was constructed and used to develop a clinical decision support system (CDSS). Prospectively, the clinical data of patients diagnosed with PJI or aseptic loosening in the Department of Orthopedics of the First Hospital of Chongqing Medical University from July 2020 to December 2022 were collected as a validation group, and the diagnostic performance of the column-line diagram model was externally validated by methods such as receiver operating characteristic curve (ROC).Results:There were 85 cases of PJI in the 181 cases modeling group and 23 cases of PJI in the 49 cases validation group. Among the 27 potential factors analyzed by lasso regression analysis, body mass index (BMI), blood tests including platelet (PLT), absolute lymphocyte value, interferon γ (IFN-γ), ESR, IL-6, C-reactive protein, D-dimer, and joint fluid tests including C-reactive protein, IL-1, IL-4, IL-6, percentage of multinucleated neutrophils (PMN%), and CD64 may be potential indicators for the diagnosis of PJI. Univariate found significant differences between hematologic tests including sedimentation, C-reactive protein, IL-6, D-dimer and joint fluid tests including C-reactive protein, joint fluid CD64 index, C-reactive protein, IL-1, IL-4, IL-6, PMN%( P<0.05). Further multifactorial regression analysis screened serum IL-6, D-dimer, joint fluid CD64 index, C-reactive protein, IL-1, IL-4, IL-6, and percentage of multinucleated neutrophils, and based on that, the column-line graph model and CDSS system were constructed. The area under the ROC in the validation group was 0.978, and the AUC in the internal validation was 0.995; the C-index of the calibration curve was 99.50%, and the C-index of the internal validation was 99.53%, suggesting that the column-line diagram model has a good predictive ability. Conclusions:The column-line diagram for diagnosing PJI based on multiple diagnostic indicators showed good diagnostic performance. The CDSS system constructed by column-line diagrams could assist clinicians in diagnosing PJI and making reasonable strategies in time.

The role of four-generation Oxford nanopore sequencing technology in searching for pathogenic bacteria in periprosthetic infection / 中华骨科杂志

Objective:To explore the application value of Oxford nanopore technologies (ONT) in the diagnosis and treatment of periprosthetic joint infection (PJI).Methods:A prospective analysis was conducted on 32 patients with PJI admitted to the joint department of Xi'an Honghui Hospital from October 2021 to March 2023, who met the 2018 PJI diagnostic criteria of the American Skeletal Infection Society (MSIS), including 15 males and 17 females with an average age of 63.93±8.93 years. 32 revision patients who did not meet the 2018 MSIS PJI criteria during the same period were collected as controls (non PJI group), including 13 males and 19 females with an average age of 65.53±8.54 years. All patients underwent joint fluid puncture before or during surgery, and the specimens were tested by ONT, metagenomic next generation sequencing (mNGS), and general microbial culture. The receiver operating characteristic (ROC) curves were drawn for both groups, and the sensitivity, specificity, positive predictive value, negative predictive value, and Youden index of the three detection techniques were calculated and compared to evaluate the detection efficiency of different detection methods in PJI.Results:Among the 32 patients with PJI, 30 were positive for ONT, with a total of 30 pathogenic bacteria detected, and the detection time was 22.37±8.36 h. 31 were positive for mNGS, with a total of 33 bacterial species detected, and the detection time was 46.25±9.36 h. 17 were positive for microbial culture, with a total of 8 bacterial species detected, and the detection time was 96.23±15.62 h. Among the 32 patients with non PJI group, 1 was positive for ONT and 5 were positive for mNGS, with a total of 1 and 3 bacterial species detected, respectively. The results of microbial culture were all negative. The detection time and area under the curve (AUC) of ONT and mNGS were 22.37±8.36 h and 0.953[95% CI (0.901, 1.006)], 46.25±9.36 h and 0.906[95% CI (0.835, 0.977)], respectively, which were better than those of microbial culture 96.23±15.62 h and 0.766[95% CI (0.678, 0.853)], and the difference was statistically significant ( P<0.05). The sensitivity of ONT, mNGS, and microbial culture were 0.938, 0.969, and 0.531, respectively, and the specificity was 0.969, 0.844, and 1.000, respectively. The Jordan index was 0.906, 0.813, and 0.531, respectively. Conclusion:ONT testing has higher diagnostic efficacy than mNGS and microbial culture in the diagnosis of PJI, and also has advantages in detection time. It also suggests that some PJI are not caused by a single microbial infection.

Investigation of the hydromechanical threshold of high-mobility group box 1 release from synovial cells and chondrocytes / 口腔疾病防治

Objective@#To investigate the effect of fluid flow shear stress (FFSS) on the fluid mechanic threshold of high-mobility group box 1 (HMGB1) release by synovial cells and chondrocytes. Moreover, the mechanism of chondrocyte and synovial cell damage induced by abnormal mechanical force was investigated to provide an experimental basis for exploring the pathogenesis and pathology of temporomandibular joint osteoarthritis.@*Methods@#With the approval of the Ethics Committee for Animal Experiments of the hospital, synovial tissue and cartilage tissue blocks were obtained from the knee joints of Sprague-Dawley (SD) rats, and synovial cells and chondrocytes were cultured and digested for subsequent experiments. Synovial cells and chondrocytes of 3-4 generations were acquired, and FFSS was applied to synovial and cartilage cells using a fluid shear mechanical device. The cells were divided according to the FFSS values of different sizes. Synovial cells were stimulated for 1 h with 1, 3, 5, or 10 dyn/cm2 of FFSS, and chondrocytes were stimulated for 1 h with 4, 8, 12, or 16 dyn/cm2 of FFSS. Resting cultures (0 dyn/cm2) were used as the control group. Changes in the morphology of the cells were observed. The expression and distribution of HMGB1 and interleukin-1β (IL-1β) were observed by immunohistochemistry. The expression of HMGB1 and IL-1β in the supernatant was analyzed by ELISA. The protein expression levels of intracellular HMGB1 and IL-1β were detected by Western blot.@*Results@#With increasing FFSS, the synovial cells and chondrocytes gradually swelled and ruptured, and the number of cells decreased. With increasing FFSS, the localizationof HMGB1 and IL-1β gradually shifted from the nucleus to the cytoplasm. In synovial cells, compared with those in the control group, the expression levels of HMGB1 and IL-1β were increased both in the supernatant and cells in the 1, 3, 5 and 10 dyn/cm2 intervention groups (P<0.01). In chondrocytes, compared with those in the control group, the expression levels of HMGB1 in the supernatant were increased in the 4, 12 and 16 dyn/cm2 intervention groups (P<0.05), and the protein expression levels of HMGB1 were significantly increased (P<0.01). The expression levels of HMGB1 in the supernatant were significantly increased in the 8 dyn/cm2 intervention groups (P<0.01); however, the protein expression levels of HMGB1 were significantly decreased. Compared with those in the control group, the expression levels of IL-1β in the supernatant gradually increased in the 4, 8, 12 and 16 dyn/cm2 intervention groups (P<0.01). With the exception of those in the 4 dyn/cm2 group, the protein expression levels of IL-1β gradually increased with increasing FFSS (P<0.05).@*Conclusion@#With increasing FFSS, synovial cells and chondrocytes gradually swelled and burst, and the hydromechanical thresholds of HMGB1 release were 1 dyn/cm2 and 8 dyn/cm2, respectively. Therefore, upon stimulation with a mechanical force, synovial damage was damaged before chondrocytes.

Effect and Mechanism of Sishenjian on Synovial Lesions in Knee Osteoarthritis Rats / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate （MIA） in rats with knee osteoarthritis （KOA）. MethodSixty female Sprague-Dawley （SD） rats were randomly divided into the following six groups： normal group， model group， celecoxib group， and high-， medium-， and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib （18 mg·kg-1） and Sishenjian （14.4， 7.2， 3.6 g·kg-1） were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured， and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin （HE） staining and picrosirius red staining. Immunohistochemistry （IHC） was used to detect the expression of vascular endothelial growth factor A （VEGFA） in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β1 （TGF-β1）/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group， the transverse diameter of the knee joint in the model group significantly increased （P<0.01）. Compared with the model group， the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the knee joint synovial fluid of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of TGF-β1， Smad2/3， phosphorylation（p）-Smad2/3， type Ⅰ collagen α1 （ColⅠα1）， type Ⅲ collagen α1 （ColⅢα1）， VEGFA proteins and TGF-β1， Smad2/3， ColⅠα1， ColⅢα1 mRNA in knee joint synovium of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of TGF-β1， Smad2/3， phosphorylation （p）-Smad2/3， ColⅠα1， ColⅢα1， VEGFA proteins and TGF-β1， Smad2/3， ColⅠα1， ColⅢα1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased （P<0.05， P<0.01）. ConclusionSishenjian can inhibit synovial inflammation and angiogenesis， and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β1/Smad2/3 pathway.

Synovial sarcoma of the liver:a case report and literature review / 解放军医学杂志

Objective To report a case of synovial sarcoma of the liver and review the literature for improving the understanding of the disease.Methods The clinical data of a patient with liver synovial sarcoma admitted to the First Affiliated Hospital of Henan University were analyzed retrospectively.The imaging,pathological features,treatment and prognosis of this disease were summarized by searching the database(CNKI,Wanfang Data,PubMed,untill July 2022)and the literature results analyzed comprehensively.Results The patient was a 71-year-old female who was admitted to the hospital due to abdominal pain.Computed tomography(CT)scan showed a mass with mixed density in the right lobe and caudate lobe of the liver.The large cross section size was about 115 mm×87 mm and the mass showed continuous heterogeneous enhancement,being considered as malignant hepatic tumors with multiple metastasis of the liver and lung.Ultrasound-guided needle biopsy was performed,and microscopy showed the tumor cells were obvious atypical,and some were spindle-shaped.Immunohistochemistry showed that the patient was positive for vimentin(VIM),epithelial membrane antigen(EMA),methylation of histone at lysine 27(H3K27Me3),and negative for pan cytokeratin(CK-pan)and S-100,and pathological diagnosis of synovial sarcoma was made.The patient did not undergo subsequent treatment and was lost to follow-up after discharge.A total of 12 cases of hepatic synovial sarcoma were reported after searching the database.The clinical manifestations were abdominal pain or distention.The lesions were mostly located in the right lobe of the liver,usually large,heterogeneous density,and heterogeneous enhancement on enhanced CT or magnetic resonance imaging(MRI).Spindle-shaped cells were found at histopathologic examination.Immunohistochemistry showed the patient was positive for VIM,EMA,H3K27Me,B-cell leukemia/lymphoma-2(BCL-2)and transducer-like enhancer of split 1(TLE1).SS18-SSX fusion gene or SS18 gene isolation were detected.Eleven patients received surgical treatment,5 received adjuvant chemotherapy,and 4 had recurrence or metastasis during the follow-up period.Conclusions Synovial sarcoma of the liver is a rare malignant tumor of the liver.The clinical and imaging features are not specific.The diagnosis depends on pathology.At present,the main treatment is surgery,and comprehensive treatment such as adjuvant chemotherapy can be performed.The prognosis of the patient is poor.

Expression Level of CCP/AST in Synovial Fluid and Synovial Tissue of Rheumatoid Arthritis Patients and Its Clinical Significance / 现代检验医学杂志

Objective To investigate the expression level and clinical significance of cyclic citrullinated peptide antigen-specific T cells(CCP/AST)in synovial fluid and synovial tissue of rheumatoid arthritis(RA)patients.Methods A total of 128 RA patients in Shijiazhuang Hospital of Traditional Chinese Medicine from January to December 2021 were selected as the RA group,and 50 patients who needed arthroscopy for joint pain in the hospital during the same period were selected as the control group.Among the RA group,there were 46 cases in the mild group,52 cases in the moderate group,and 30 cases in the severe group.The protein expression levels of rheumatoid factors(RF)and anticitrullinated protein antibodies(ACPA)in synovial tissues of the subjects in each group were analyzed by Western blot.The frequency of CCP/AST in the synovial fluid of the subjects was analyzed by flow cytometry.The intensity of the staining of CCP/AST in synovial tissues was observed by double immunofluorescence staining/laser confocal scanning.Pearson correlation analysis was used to assess the correlation between the CCP/AST expression of synovial fluid and synovial tissue and RF and ACPA.Logistic regression was used to analyze the risk factors for the development of rheumatoid arthritis.Results In the order of control,mild,moderate and severe groups,RF(1.01±0.01,1.53±0.03,2.01±0.08,2.66±0.12 kDa)and ACPA proteins(1.03±0.01,1.61±0.03,2.04±0.10,2.59±0.13 kDa)in synovial tissues of patients were sequentially elevated,and the differences were all statistically significant(F=14.207,12.446,all P＜0.05).The expression of CCP/AST in synovial fluid of patients in the control,mild,moderate and severe groups was increased sequentially(8.26%±1.68%,22.46%±3.28%,33.58%±4.37%,46.15%±5.44%),and the difference was statistically significant(F=25.306,P＜0.05).Meanwhile,the intensity of CCP/AST staining in synovial tissues of patients in the control,mild,moderate and severe groups was also increased sequentially(1.05±0.26,1.35±0.89,2.04±0.56,2.78±0.15 score),and the difference was statistically significant(F=70.67,P＜0.05).The expression of CCP/AST in the synovial fluid and synovial tissues of patients with RA was positively correlated with RF(r=0.861,0.934,all P＜0.05)and ACPA in synovial fluid and synovial tissue(r=0.854,0.913,all P＜0.05).Logistic regression analysis showed that hypertension(OR=3.241,95%CI:1.491～6.752),diabetes mellitus(OR=2.565,95%CI:1.126～5.813),synovial fluid(OR=4.450,95%CI:1.652～11.622),and CCP/AST expression in synovial tissues(OR=5.629,95%CI:2.474～12.390)were independent risk factors for the development of RA(P＜0.05).Conclusion CCP/AST showed high expression in synovial fluid and synovial tissue of RA patients and related to disease activity and joint destruction,which can be used to assess the clinical joint mobility and bone destruction degree in such patients.

Mangiferin inhibits proliferation,migration and inflammatory factor expression of fibroblast-like synoviocytes in rheumatoid arthritis / 中国组织工程研究

BACKGROUND:Mangiferin is a biphenylpyridone compound extracted from mango leaves,bark and roots.Previous studies have shown that mangiferin can exert anti-systemic inflammatory effects through the activation of transcription factors such as NF-κB and JAK/STAT. OBJECTIVE:To investigate the effects and mechanisms of mangiferin on proliferation,migration and inflammatory factor release of rheumatoid arthritis fibroblast-like synovial cells(RA-FLS). METHODS:RA-FLS were divided into blank group,R848(TLR7/8 agonists)stimulated group,mangiferin low-,medium-,high-dose groups(2,4 and 8 μg/mL)and positive control group(Cu-CPT8,TLR8 pathway inhibitor).The cytotoxic effect of different mass concentrations of mangiferin was detected using cell counting kit-8 method and the final cellular dosing mass concentration was screened.The proliferation ability of RA-FLS was detected by cell clone formation assay,the migration ability of RA-FLS was detected by scratch assay and Transwell migration assay,and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA in RA-FLS was detected by qRT-PCR. RESULTS AND CONCLUSION:Compared with the blank group,the viability of RA-FLS was inhibited after treatment with mangiferin at 2-10 μg/mL,but there was no significant difference among groups(P>0.05),indicating that the toxic effect on RA-FLS was minimal.Compared with the R848-stimulated group,mangiferin decreased the number of cell clones,the scratch healing rate and the number of migrating cells in all dosing groups(P<0.01);and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA was also reduced in the mangostin medium-and high-dose groups(P<0.01).Compared with the R848-stimulated group,the number of cell clones,the scratch healing rate and the number of migrating cells as well as the expression levels of interleukin 6 and tumor necrosis factor α mRNA were significantly reduced in the positive control group(P<0.05,P<0.01).But there was no significant difference in the expression level of interleukin 1β.To conclude,mangiferin may exert its anti-rheumatoid arthritis effects through the TLR7/8 signaling pathway by inhibiting RA-FLS proliferation,migration,and inflammatory factor release.

Mechanism by which miR-34a-5p/PLCD3 axis regulates osteoarthritis progression / 中国组织工程研究

BACKGROUND:Molecular mechanisms targeting the miRNA/mRNA axis to regulate osteoarthritis disease process have been studied.We identified the mRNA:phospholipase C delta 3(PLCD3)and its target miRNA(miR-34a-5p)with clinical predictive value through previous bioinformatics studies,while experiments to verify their specific roles and mechanisms in regulating osteoarthritis are still lacking. OBJECTIVE:To investigate the regulatory role and mechanism of miR-34a-5p/PLCD3 axis on osteoarthritis progression. METHODS:The synovium of 15 patients with knee osteoarthritis was selected as the osteoarthritis group,and the synovium of 15 young patients with internal fixation of patellar fracture caused by trauma during the same period was selected as the control group.The expression of PLCD3 and miR-34a-5p in the synovium was detected by real-time PCR.Human fibroblast like synovial cells-osteoarthritis(HFLS-OA)cells were treated by cell transfection and divided into miR-34a-5p mimic group,pCDH-PLCD3 group,miR-34a-5p mimic+pCDH-PLCD3 group,miR-34a-5p inhibitor group,si-PLCD3 group,and miR-34a-5p inhibitor+si-PLCD3 group.The relationship between PLCD3 and miR-34a-5p expression was detected by real-time PCR.The effects of HFLS-OA cell viability and cell migration in each group were detected by CCK-8 assay and cell scratch test.Western blot assay was used to detect the expression level of apoptosis marker protein.The expression of inflammatory factors was detected by ELISA. RESULTS AND CONCLUSION:(1)PLCD3 was a direct target of miR-34a-5p,and the expression levels of PLCD3 and miR-34a-5p were negatively correlated.(2)Upregulation of PLCD3 promoted proliferation of HFLS-OA cells and inhibited cell migration.The up-regulation of miR-34a-5p significantly inhibited the activity of HFLS-OA cells and enhanced cell migration.Overexpression of miR-34a-5p significantly increased the levels of Casp3 and Casp9 proteins in HFLS-OA cells,while overexpression of PLCD3 showed the opposite trend.(3)PLCD3 overexpression significantly increased the expression of interleukin 6 and tumor necrosis factor alpha in HFLS-OA cells,while miR-34a-5p mimics showed protective activity.(4)The miR-34a-5p/PLCD3 axis may affect the progression of osteoarthritis by regulating the inflammatory process or apoptosis of synovial cells.

Improvement effect and mechanism of “Layers adjusting external application”paste on synovial fibrosis in rats with knee osteoarthritis / 中国药房

OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

Synovial sarcoma of the Hypopharynx in a Filipino female: A case report

@#Synovial sarcoma of the hypopharynx is an uncommon malignancy, with less than 100 cases reported in available journals. We report a case of a 22-year-old female presenting with dysphagia and enlarging hypopharyngeal mass, clinically diagnosed as hypopharyngeal malignancy, right, at least stage III. Histopathologic examination including immunohistochemistry study with TLE1 and SS18 Fluorescence In Situ Hybridization (FISH) confirm the diagnosis of synovial sarcoma. This is the first reported case of synovial sarcoma of the hypopharynx in the Philippines confirmed by SS18 FISH. Due to the size of the mass, chemoradiotherapy followed by surgery is the current plan of management for this patient.

The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study

Abstract Background: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. Methods: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. Results: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. Conclusion: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB approval number: 23115 012030/2009-05.

Resultados oncológicos y factores pronósticos en pacientes con sarcoma sinovial tratados quirúrgicamente / Oncological outcomes and prognostic factors in surgically treated patients with synovial sarcoma

Resumen Introducción : El sarcoma sinovial es un tumor raro (incidencia de 1-3 casos por millón). Es más frecuente en adolescentes y adultos menores de 30 años. Se desarrolla en cualquier parte del cuerpo, siendo, las extremidades el lugar más frecuente de aparición (80% extremidades y 20% otras localizaciones: 8% tronco, retroperitoneal/ abdominal 7%, cabeza y cuello 5%). Los resultados on cológicos de los pacientes con sarcoma sinovial son disímiles. La tasa de supervivencia libre de recurrencia local, la supervivencia libre de eventos y la superviven cia global varían entre las series publicadas. Lo mismo sucede con los factores pronósticos de la enfermedad. Métodos : El objetivo fue analizar un grupo de 43 pacientes con diagnóstico de sarcoma sinovial de las extremidades tratados quirúrgicamente, y determinar (1) tasa de supervivencia global, (2) tasa de superviven cia libre de eventos, (3) tasa de recurrencia local y (4) factores de riesgo oncológicos. Resultados : La supervivencia global a los 2 años fue 90% (IC95%: 76-96%), y 67% (IC95%: 49-80%) a los 5 años. La supervivencia libre de eventos a los 2 años fue 68% (IC95% 51-80%) y a los 5 años 48% (IC95% 32-52%). El riesgo de recurrencia local a 2 años fue 9% (IC95% 3-25%) y a los 5 años 25% (IC95% 13-46%). Los factores de mal pronóstico oncológico fueron el grado histológico y la presencia de metástasis. Discusión : Podemos concluir que nuestros resulta dos oncológicos se asemejan a las series publicadas y que en nuestra serie hubo dos factores de mal pro nóstico.

Abstract Introduction : Synovial sarcoma is an unusual tumor with an incidence of 1-3 cases per million. It is more frequent in teenagers and young adults under 30. It develops anywhere, but the extremities are the most frequent place of appearance (80% extremities, 20% other locations: 8% trunk, 7% retroperitoneal/abdominal, 5% head and neck). Oncological results are different depending on the study. Survival rate free of local recur rence, survival rate free of events and global survival rate vary upon published studies. The same happens with the disease's prognostic factors. Methods : The objective was to analyze a group of 43 patients with diagnosis of synovial sarcoma of the extremities treated surgically and determine (1) global survival rate, (2) survival rate free of events, (3) local recurrence rate and (4) oncological risk factors. Results : The global survival rate at 2 years was 90% (IC95%: 76 - 96%) and 67% (IC95%: 49-80%) at 5 years. The survival rate free of events at 2 years was 68% (IC95% 51-80%) and 48% (IC95% 32-52%) at 5 years. The recurrence rate at 2 years was 9% (IC95% 3-25%) and 25% (IC95% 13-46%) at 5 years. The histological grade and metastatic presence were bad prognostic factors. Discussion : We can conclude that our oncological results are in line with those published in previous series and that there were two factors associated with poor prognosis.

Sarcoma sinovial primario de pericardio / Primary pericardial synovial sarcoma

Resumen El sarcoma sinovial primario del pericardio es un tumor muy raro y de mal pronóstico y se sabe poco en cuanto al manejo terapéutico. Presentamos el caso de una paciente de 51 años a quien se le realizó resección quirúrgica incompleta, quimioterapia y radioterapia. Hasta donde sabemos, este es el primer caso de un sarcoma sinovial primario de pericardio que luego de operado se mantuvo asintomático durante 5 años hasta que en una TAC de control se le detectaron metástasis cardiacas que comprometían las cavidades derechas y con quimioterapia, la ecocardiografía demostró la reso lución completa de las mismas.

Abstract Primary pericardial synovial sarcoma is an extraor dinarily very rare tumor with a poor prognosis, and little is known about its therapeutic management. We describe the case of a 51-year-old woman patient who underwent incomplete surgical resection, chemotherapy, and radiotherapy. To the best of our knowledge, no pri mary pericardial synovial sarcoma has been described which, after surgery, remains asymptomatic for 5 years, and until a control CT scan detects cardiac metastases that compromised the lumen of the right cavities and with chemotherapy, echocardiography demonstrated complete resolution of cardiac metastases.

Estudio de los pacientes con monoartritis aguda en un hospital de tercer nivel / Acute monoarthritis in a third level hospital

Resumen Introducción: La monoartritis aguda (MA) represen ta una causa relevante de morbilidad que requiere de atención médica oportuna: El estudio del líquido sino vial constituye un elemento clave para su diagnóstico. El objetivo del estudio fue determinar la frecuencia y características clínicas-analíticas de los episodios de MA y bursitis agudas valoradas en un hospital durante un período de 6 años. Métodos: Estudio analítico retrospectivo de corte transversal en un hospital de Córdoba, Argentina. Se identificaron todos los episodios de monoartritis y bur sitis agudas que ocurrieron en pacientes de ≥18 años entre 2012 y 2017. Se excluyeron los cuadros de MA en embarazadas y las monoartritis crónicas. Resultados: Se incluyeron 180 episodios de MA y 12 de bursitis aguda. Entre las MA, 120 (66.7%) ocurrieron en hombres, la edad promedio fue 62.1±16.9 años. La principal causa de MA fue séptica, identificándose 70 (36%) casos, seguida la secundaria a microcristales con 54 episodios (28%) que correspondieron 27 (14%) a MA por gota y 27 (14%) a MA por depósitos de pirofosfato de calcio dihidratado (CPPD). Se identificaron cristales de urato monosódico en 26 (14.3%) pacientes, CPPD en 28 (15.6%) y de colesterol en 1 (0.6%). Discusión: La principal causa de MA fue séptica, seguida de la secundaria a microcristales (gota y secun daria a CPPD). La principal articulación afectada fue la rodilla, seguida del hombro. El análisis del líquido sino vial fue un elemento clave a la hora de poder realizar el diagnóstico diferencial entre las distintas causas de monoartritis aguda y bursitis.

Abstract Introduction: Acute monoarthritis (AM) represents a relevant cause of morbidity that requires prompt medical care. The study of synovial fluid becomes re levant to allow a rapid diagnostic approach. The main objective of the study was to determine the frequency and clinical-analytical characteristics of episodes of AM and acute bursitis evaluated in a hospital during a period of 6 years. Methods: Cross-sectional retrospective analytical study in a hospital at Córdoba, Argentina. All episodes of acute monoarthritis and bursitis that occurred in patients aged 18 years or older between 2012 and 2017 were included. AM in pregnant women and chronic monoarthritis were excluded. Results: One hundred and eighty episodes of AM and 12 of acute bursitis were included. Among the AM, 120 (66.7%) occurred in male patients and the average age was 62.1±16.9 years. The main cause of AM was septic, identifying 70 (36%) cases, followed by microcrystalline AM identify 54 (28%) cases, which corresponded to gout and calcium pyrophosphate dihydrate (CPPD) with 27 (14%) cases each one. Monosodium urate crystals were identified in 26 (14.3%) patients, CPPD in 28 (15.6%) and cholesterol in 1 (0.6%). Discussion: The main cause of AM was septic arthri tis, followed by microcrystalline AM (gout and secondary to CPPD). The main affected joint was the knee, followed by the shoulder. Synovial fluid analysis was a key ele ment when making the differential diagnosis between the different causes of acute monoarthritis and bursitis.

A rare case of smear positive tuberculous arthritis

TB arthritis is a very rare extrapulmonary presentation in an immunocompetent host. It is usually the result of direct hematogenous spread from the primary focus. Our patient presented with pain and swelling of the right knee for 6 months. The blood investigations and CT chest revealed findings consistent with active tuberculosis. Synovial fluid was positive for acid-fast bacilli (AFB) which is a very rare finding. Cartridge-based nucleic acid amplification test (CBNAAT) revealed Mycobacterium tuberculosis and sensitivity to rifampicin. Establishing the diagnosis of Mycobacterium tuberculosis beyond doubt is very important, and early initiation of antitubercular treatment (ATT) is important as delay in treatment may lead to irreversible damage to the joint and restriction of joint mobility.

Neumotórax espontáneo persistente como manifestación primaria de sarcoma sinovial pleuropulmonar primario: a propósito de un caso / Persistent spontaneous pneumothorax as a primary manifestation of primary synovial sarcoma of the lung: a case report

El sarcoma sinovial pleuropulmonar (SSPP) es un tumor primario de pulmón, maligno, infrecuente en pediatría (prevalencia 0,1-0,5 %) que afecta predominantemente a adolescentes y adultos jóvenes. Se ha descrito una sobrevida global cercana al 30 % a los 5 años. Se reporta el caso de un paciente de 12 años de edad, previamente sano, que presentó tos, dolor torácico y disnea de comienzo súbito, como manifestación inicial de neumotórax izquierdo, el que persistió a los 4 días y requirió resección quirúrgica de lesión bullosa pulmonar. Se realizó diagnóstico histológico de sarcoma sinovial pleuropulmonar confirmado por estudio molecular, que evidenció la translocación cromosómica entre el cromosoma X y el 18: t(X;18) (p11.2;q11.2) de la pieza quirúrgica extirpada. Ante pacientes con neumotórax persistente o recidivante, es importante descartar causas secundarias, entre ellas, sarcoma sinovial pleuropulmonar. Su ominoso pronóstico determina la necesidad de arribar a un diagnóstico temprano e implementar un tratamiento agresivo

Pleuropulmonary synovial sarcoma (PPSS) is a primary malignancy of the lung, uncommon in pediatrics (prevalence: 0.1­0.5%) that predominantly affects adolescents and young adults. Overall survival has been reported to be close to 30% at 5 years. Here we report the case of a previously healthy 12-year-old male patient who presented with cough, chest pain, and dyspnea of sudden onset as initial manifestation of left pneumothorax, which persisted after 4 days and required surgical resection of pulmonary bullous lesion. A histological diagnosis of pleuropulmonary synovial sarcoma was made and confirmed by molecular study, which showed chromosomal translocation between chromosomes X and 18: t(X;18) (p11.2;q11.2) in the surgical specimen removed. In patients with persistent or recurrent pneumothorax, it is important to rule out secondary causes, including pleuropulmonary synovial sarcoma. Such poor prognosis determines the need for early diagnosis and aggressive treatment.

Treatment of Wrist Dorsal Synovial Cyst with Percutaneous Sclerotherapy Using Hypertonic Saline Solution / Tratamento de cisto sinovial dorsal do punho com escleroterapia percutânea utilizando solução salina hipertônica

Abstract Objective To evaluate the efficacy of hypertonic saline infiltration as a sclerosing agent in the dorsal synovial cyst of the wrist. Method Patients of both genders, aged 18 years or older, with clinical and ultrasound diagnosis of synovial cyst, and without any previous treatment were selected. Case series in which 50 patients underwent aspiration of the contents of the cyst and infiltration of the hypertonic saline solution (2 ml sodium chloride solution 20% and 1 ml of lidocaine 2%). The patients were followed up for 24 weeks, when the parameters pain, strength, range of motion, function (quickDASH and Brief Michigan question), recurrence, and complications were evaluated. Results A total of 46 patients were evaluated for 24 weeks, 18 (39.1%) cysts evolved to resolution, and 28 (60.9%) presented recurrence. There was no statistically significant difference in the effect force or in the range of motion. There was no clinically significant difference in the scores of the questionnaires. The most frequent complications were pain and edema. Conclusion Infiltration with hypertonic saline solution for the treatment of dorsal synovial cyst of the wrist showed a recurrence rate of 60.9%.

Resumo Objetivo Avaliar a eficácia da infiltração da solução salina hipertônica como agente esclerosante no cisto sinovial dorsal do punho. Método Pacientes de ambos os sexos, com 18 anos ou mais, com diagnóstico clínico e ultrassonográfico de cisto sinovial, e sem nenhum tratamento prévio foram selectionados. Série de casos em que 50 pacientes foram submetidos a aspiração do conteúdo do cisto e infiltração da solução salina hipertônica (2 ml solução de cloreto de sódio 20% e 1 ml de lidocaína 2%). Seguimento realizado por 24 semanas, durante as quais foram avaliados os parâmetros dor, força, arco de movimento, função (questionários quick disabilities of the arm, hand, and shoulder [quickDASH] e brief Michigan), recorrência e complicações. ResultadoForam avaliados 46 pacientes por 24 semanas, 18 (39,1%) cistos evoluíram para cura e 28 (60,9%) cistos apresentaram recorrência. Não houve diferença estatisticamente significante nos quesitos força e arco de movimento. Não houve diferença clinicamente significante nos escores dos questionários. As complicações mais frequentes foram dor e edema. Conclusão A infiltração com solução salina hipertônica para tratamento do cisto sinovial dorsal do punho mostrou taxa de recorrência de 60,9%.

Correlation of characteristic gene and immune infiltration of rheumatoid arthritis based on bioinformatics and machine learning / 中国免疫学杂志

Objective:To explore pathogenesis,characteristic genes and immune infiltration of rheumatoid arthritis(RA)by bioinformatics and machine learning methods,and to find correlation between characteristic genes and immune cells.Methods:Chips related to RA were obtained from GEO database,gene differences were analyzed by R language,and GO and KEGG were enriched and analyzed;machine learning methods,namely LASSO regression and SVM-RFE were used to screen disease characteristic genes,ROC curve and sample chips were used to detect accuracy of characteristic genes,CIBERPORT algorithm was used to analyze immune infiltration of RA,and correlation between characteristic genes and immune cells was analyzed.Results:A total of 90 differen-tial genes were obtained from GSE12021 and GSE55235,including 64 up-regulated and 26 down-regulated differentially expressed genes.A total of 209 main items were obtained by GO analysis,mainly involving leukocyte activation,lymphocyte activation,B-cell receptor signaling pathway,etc;KEGG analysis showed that chemokine signaling pathway,IL-17 signaling pathway,Toll-like recep-tor signaling pathway and PPAR signaling pathway were closely related to RA;ten key genes such as IGHM,SLAMF8,CXCL10,FNDC4,AIM2,EGR1 and AKR1B10 were screened by mechanical learning method.Disease characteristic genes were IGHM,SLAMF8,CXCL10,AIM2 and AKR1B10 by ROC curve and sample chip;immune infiltration results showed that there were signifi-cant differences between synovial tissues of RA and normal tissues in 9 kinds of immune cells,such as plasma cells,CD8 T cell,CD4 T cell and T cell follicle helper.By analyzing correlation between disease characteristic genes and immune cells,it was found that there were significant correlations between 5 characteristic genes and some immune cells.Conclusion:There is a significant correla-tion between characteristic genes and immune cells of RA,which provides a preliminary basis for follow-up in-depth study of targeted diagnosis and treatment of RA.