1.Effect of leflunomide regulating HIF-1α signal pathway on autophagy of synoviocytes in rheumatoid arthritis
Weiya LAN ; Wukai MA ; Xueming YAO ; Zong JIANG ; Lang XIONG ; Shufen YANG ; Fang TANG
Acta Universitatis Medicinalis Anhui 2024;59(10):1823-1828
Objective To investigate the effect of leflunomide(LEF)on the expression of associated autophagy genes in synoviocytes of rheumatoid arthritis(RA)by regulating HIF-1α signal pathway.Methods Three genera-tions of RA synovial cells were divided into blank control group,LEF group and Tripterygium wilfordii polyglyco-sides group.The blank control group was added with the same volume of DMEM culture medium.The drug group was treated with LEF(concentration 0.2 mg/ml)and Tripterygium wilfordii polyglycosides(concentration 0.03 mg/ml),the proliferation and apoptosis of synovial cells were detected by flow cytometry,the expression of IL-1 β,TNF-α,ANGPTL-4 and VEGF was detected by ELISA,the expression of HIF-1α mRNA was detected by qRT-PCR,and the expression of HIF-1 α,Beclin-1 and BNIP3 protein was detected by Western blot.Results Com-pared with Tripterygium wilfordii polyglycosides group,the expression of IL-1 α,TNF-α,ANGPTL-4 and VEGF in synovial supernatant of LEF group decreased;compared with the blank control group,the expression of HIF-1αmRNA in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious;compared with the blank control group,the protein expressions of HIF-1α,Bec-lin-1 and BNIP3 in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious.Conclusion LEF can inhibit the expression of inflammatory factors in RA synovial cells,inhibit HIF-1α signaling pathway,inhibit the expression of autophagy-related genes Beclin-1 and BNIP3,and improve the pathological state of synovitis.
2.Microbiomes combined with metabolomics reveals the changes of microbial and metabolic profile of articular cavity effusion in rheumatoid arthritis, urarthritis and osteoarthritis patients
Hanzhi Yi ; Wukai Ma ; Minhui Wang ; Chunxia Huang ; Guangzhao Gu ; Dan Zhu ; Hufan Li ; Can Liu ; Fang Tang ; Xueming Yao ; Liping Sun ; Nan Wang ; Changming Chen
Acta Universitatis Medicinalis Anhui 2024;59(12):2237-2245
Objective:
To investigate the changes of microorganisms and metabolites in joint effusion of patients with Rheumatoid arthritis(RA), Osteoarthritis(OA) and Urarthritis(UA). To provide new ideas for the study of the effect of microbiota on the pathogenesis of arthritis.
Methods:
Joint effusion samples were collected from 20 patients with RA, 20 patients with OA, and 20 patients with UA. 16S rRNA gene sequencing and untargeted ultra-high performance Liquid chromatography-mass spectrometry(LC-MS) were used to explore the differences in microorganisms and metabolites among the three groups. Pearson correlation analysis was used to detect the correlation between effusion microbiota and metabolites.
Results:
There were differences in microbial diversity and microbiota composition among the three groups. Combined with VIP>1 from OPLS-DA andP<0.05 from two-tailed Students t-test, 45 differential metabolites(Between RA and OA groups), 38 differential metabolites(Between UA and OA groups) and 16 differential metabolites(Between RA and UA groups), were identified. GO analysis and KEGG pathway analysis showed that the differential metabolic pathways among the three groups were mainly concentrated in citric acid cycle(TCA cycle), nucleotide metabolism, amino acid metabolism and glycolysis pathway. Correlation analysis of joint effusion microbiota and metabolites suggested that bacteria enriched in the three groups of joint effusion, such asPrevotella,Clostridium ruminosus,Prevotellaceae_UCG-001, were related to many key metabolites such as lysozyme, uric acid, glucose, and L-glutamine.
Conclusion
This study shows that there are a variety of bacterial flora in joint cavity effusion of RA, OA, and UA patients, and the differential metabolites produced by them are involved in the pathogenesis of the three types of arthritis by affecting a variety of metabolic pathways.
3.Risk factors for prolonged ICU stay after surgery in patients with infective endocarditis
Lili TANG ; Xueming LI ; Liming LEI ; Xiaodong ZENG ; Yun LING ; Qiongyu LIN ; Sumin ZHU
The Journal of Practical Medicine 2024;40(20):2854-2859
Objective Analyzing risk factors for prolonged ICU stay after cardiac surgery of Infective Endocarditis(IE)provides a basis for preventing extended ICU durations in postoperative IE cases.Methods From January 1,2019,to March 31,2021,a total of 223 patients with infective endocarditis who underwent cardiac surgery in the cardiac surgery department of Guangdong Provincial People's Hospital were included.Patients were divided into non-prolonged group(<3 days)and prolonged group(≥3 days)based on postoperative ICU stay duration.There were 156 cases in the non-prolonged group and 67 cases in the prolonged group.Single-factor analysis of risk factors for prolonged ICU stay was conducted using t-tests or rank-sum tests.Variables with P<0.05 in the single-factor analysis were further subjected to binary logistic regression for multivariate analysis.The accuracy of the model was evaluated using the ROC curve.Results Among the 223 patients,67 experienced prolonged ICU stay,with an incidence rate of 30%.Single-factor analysis results included gender,age,history of coronary heart disease,history of stroke,preoperative heart failure,aortic valve regurgitation area,left ventricular end-diastolic diameter,left ventricular ejection fraction(LVEF)<60%,extracorporeal circulation time,aortic cross-clamp time,use of Intra-Aortic Balloon Pump(IABP),endotracheal tube reintubation,pulmonary infection,use of Continuous Renal Replacement Therapy(CRRT),and prolonged mechanical ventilation time(>24 hours),among others.Multivariate analysis results revealed that preoperative LVEF<60%(OR=3.004,P=0.041),postopera-tive use of IABP(OR=31.686,P=0.008),and mechanical ventilation time>24 hours(OR=8.135,P<0.001)were independent risk factors for prolonged ICU stay after cardiac surgery.The model's AUC value for predicting risk factors for prolonged ICU stay was 0.858(95%CI:0.806~0.901,P<0.001).Conclusion Preoperative left ventricular ejection fraction(LVEF)<60%,the use of IABP,and mechanical ventilation time>24 hours were identified as independent risk factors for prolonged ICU stay after infective endocarditis(IE)surgery.In clinical practice,it is important to comprehensively address and manage various risk factors with the aim of reducing ICU stay duration and improving the overall success rate of the surgery.
4.Comparison of clinical and injured vertebra radiological parameters between patients with non-traumatic osteoporotic vertebral compression fracture and those with traumatic one after percutaneous vertebroplasty
Benqiang TANG ; Xueming CHEN ; Libin CUI ; Yanhui WANG ; Xin YUAN ; Yadong LIU ; Peng ZHAO ; Liang LIU
Chinese Journal of Orthopaedic Trauma 2024;26(11):956-963
Objective:To explore the differences in clinical and injured vertebra radiological parameters between patients with non-traumatic osteoporotic vertebral compression fracture (OVCF) and those with traumatic OVCF after percutaneous vertebroplasty (PVP).Methods:A retrospective study was conducted to analyze the 369 OVCF patients (with 458 vertebrae injured) who had been treated by PVP at Department of Orthopaedics, Beijing Luhe Hospital between October 2015 and March 2017. There were 292 females and 77 males with a mean age of 73 (60, 79) years. Based on the absence or presence of a trauma history, the patients were stratified into a non-traumatic group (127 patients with 160 vertebrae injured) and a traumatic group (242 patients with 298 vertebrae injured). Clinical parameters [age, gender, body mass index, symptomatic duration, and number of injured vertebrae, visual analogue scale (VAS), Oswestry disability index (ODI), duration of follow-up, and rate of new OVCFs] and injured vertebra radiological parameters (position of injured vertebra, fracture type, compression severity, fracture range, cortical defect, intravertebral cleft, spinal canal compromise, basivertebral foramen, morphology of bone cement, range of bone cement, cement leakage, cement volume, rate of vertebral height restoration, recollapse of cemented vertebrae) were recorded perioperatively. All the clinical and radiological parameters were compared between the 2 groups.Results:Compared with the traumatic group, the non-traumatic group had an older age [75 (71, 83) years versus 71 (65, 76) years], more females (85.0% versus 76.0%), a longer symptomatic duration [10.0 (7.0, 15.0) d versus 6.5 (2.0, 12.0) d], a lower preoperative VAS pain score [7 (6, 8) points versus 7 (7, 8) points], a lower VAS pain score at postoperative day 1 [2 (2, 3) points versus 2 (2, 3) points], a lower preoperative ODI [66% (63%, 72%) versus 70% (65%, 73 %)], a lower ODI at postoperative day 1 [32% (30%, 34%) versus 32% (31%, 34%)], a higher rate of new OVCFs during follow-up (34.6% versus 12.8%), a lower rate of thoracolumbar lesions (51.9% versus 70.1%), more deformed fractures (mostly amphicoelous type), a lower rate of cortical defects in the anterior wall (20.0% versus 31.5%), a higher rate of trabecular pattern of cement (83.1% versus 71.8%), a higher rate of type-B cement leakage (50.6% versus 31.9%), a lower rate of type-C cement leakage (5.6% versus 12.8%), a lower rate of recollapse of cemented vertebrae (43.8% versus 55.4%). All the comparisons above were statistically significant ( P<0.05). There were no significant differences between the 2 groups in the other clinical or radiological parameters ( P>0.05). Conclusions:There are statistically significant differences in a significant number of clinical and injured vertebra radiological parameters between patients with non-traumatic OVCF and those with traumatic OVCF after PVP. It is noteworthy that non-traumatic OVCFs are one specific subgroup of OVCFs.
5.Association between polarization status of microglia/macrophage in brain tissue and edema around hematoma in patients with acute cerebral hemorrhage
Xueming SHEN ; Xiupeng HAN ; Chao HE ; Yanjun TANG ; Song HAN ; Changxiang YAN
Journal of Xinxiang Medical College 2023;40(12):1161-1166
Objective To explore the correlation between polarization status of microglia/macrophages(MG/MP)in brain tissue and edema around hematoma in patients with acute cerebral hemorrhage.Methods A total of 52 patients with acute intracerebral hemorrhage admitted to Anyang People's Hospital from December 2020 to November 2022 were selected as the research subjects.All patients underwent craniotomy to remove hematoma,and the normal brain tissue in the cortical area that was not invaded by the hematoma and the fragmented brain tissue around the hematoma(brain tissue around the hematoma)on the surgical pathway were obtained.The expression levels of inflammatory factors such as interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),IL-10 and transforming growth factor-β(TGF-β)protein in brain tissue were detected by Western blot.The expression levels of IL-1 β,IL-6,TNF-α,IL-10 and TGF-β mRNA in brain tissue were detected by fluorescence quantitative polymerase chain reaction.The levels of M1-type and M2-type MG/MP in brain tissue was detected by immunofluorescence confocal technique.CT images data of patients before operation were collected and the relative-erihema-tomal edema(r-PHE)was calculated.The patients were divided into high r-PHE group(2.0≤ r-PHE<2.5)and low r-PHE group(1.5<r-PHE<2.0)according to r-PHE.The relative expression of IL-1 β,IL-6,TNF-α,IL-10 and TGF-β mRNA in brain tissue around the hematoma of patients between the high r-PHE group and the low r-PHE group was compared.Results The relative expressions of IL-1 β,IL-6,TNF-α protein and mRNA in brain tissue around the hematoma were significantly higher than those in the normal brain tissues(P<0.05),but there was no significant difference in the relative expressions of IL-10 and TGF-β protein and mRNA between the brain tissue around the hematoma and the normal brain tissue(P>0.05).The levels of M1 type and M2 type MG/MP in the brain tissue around the hematoma were significantly higher than those in normal brain tissue(P<0.05).The relative expressions of IL-1β,IL-6 and TNF-α mRNA in the brain tissue around the hematoma of patients in the high r-PHE group were significantly higher than those in the low r-PHE group(P<0.05),and there was no significant difference in the relative expressions of TGF-β and IL-10 mRNA in the brain tissue around the hematoma of patients between the two groups(P>0.05).Conclusion The levels of pro-inflammatory factors and M1-type MG/MP are increased in the brain tissue around the hematoma in patients with acute cerebral hemorrhage,and the degree of polarization of M1-type MG/MP is consistent with the degree of edema around hematoma after cerebral hemorrhage.
6.Combining electromyographic biofeedback with extracorporeal shockwave therapy can better relieve lower limb spasticity and improve the motor functioning of children with spastic cerebral palsy
Xueming LI ; Meng LIU ; Kui WANG ; Yan TANG ; Yun ZHOU
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(10):917-921
Objective:To explore the effect of combining extracorporeal shockwave therapy (ESWT) with electromyographic biofeedback on the motor functioning of children with spastic cerebral palsy.Methods:Fifty children with spastic cerebral palsy (2-7 years old) were randomized into a control group and an experimental group, each of 25. Both groups received routine rehabilitation and electric stimulation therapy with electromyographic biofeedback, while the experimental group was additionally provided with ESWT. Before and after 8 weeks of treatment, integral electromyograms were recorded and the root mean square values of the electromyogram recorded from the tibialis anterior muscle were computed. Lower limb spasticity and motor ability were evaluated by using the Modified Ashworth Scale (MAS), the Modified Tardieu Scale (MTS), and the D and E regions of the Gross Motor Function Measurement Scale (GMFM-88).Results:After the treatment the results of both groups had improved significantly in terms of the surface electromyography of the tibialis anterior muscle, MAS scores, R1 in the MTS and the difference between R2 and R1, and the GMFM-88 regional scores. All of the improvements were significantly greater in the experimental group than in the control group, on average.Conclusions:Combining ESWT with EMG biofeedback can better relieve lower limb spasticity and improve the motor functioning of children with spastic cerebral palsy.
7.Experimental study on the treatment of rheumatoid arthritis associated interstitial pulmonary disease with JAK inhibitor tofacitinib
Zong Jiang ; Xiaoling Yao ; Fang Tang ; Wukai Ma ; Weiya Lan ; Xueming Yao ; Yang An ; Zhengqi Liu
Acta Universitatis Medicinalis Anhui 2023;58(5):819-823
Objective:
To observe the effects of the tofacitinib on interstitial lung disease( ILD) by regulating the JAK⁃STAT signaling pathway.
Methods:
Wistar rats were randomly divided into 4 groups:normal group , ILD group ,prednisone acetate group , and tofacitinib group. Except for the normal group , the other three groups were given 3mg/ml bleomycin solution for modeling. After 28 days of intragastric administration , the lung tissues of all rats were
collected for hematoxylin⁃eosin staining ( HE) and Western blot ( WB) to detect the protein levels of JAK1 and STAT1;Enzyme⁃linked immunosorbent assay(ELISA) was used to detect tumor necrosis factor in rat serum (TNF) Ⅳ α , interleukin (IL) Ⅳ6 , IL⁃10 , IL⁃1β .
Results :
HE staining of lung tissue in ILD ,prednisone acetate group and tofacitinib group showed alveolar tissue thickening , alveolar wall capillary congestion , bronchial luminal epithelial cells shedding, and inflammatory cell exudation. The results of WB showed that JAK1 and STAT1 significantly increased in ILD group , and decreased in different degrees compared with ILD group , tofacitinib group and prednisone acetate group (P < 0. 05) . The ELISA results showed that the expressions of serum TNF⁃α , IL⁃6 and IL⁃1β in the ILD group were significantly higher than those in the normal group (P < 0. 01) . The expression of pine group decreased (P < 0. 05) , and the expression of IL⁃10 was the opposite.
Conclusion
Tofacitinib reduces lung tissue damage and the inflammatory response in the treatment of ILD by inhibiting the JAK⁃STAT pathway and down⁃regulating the expression of inflammatory factors TNF⁃α , IL⁃6 , IL⁃1β and up⁃regulating the anti⁃inflammatory factor IL⁃10.
8.The distribution of bone cement in the vertebral body after percutaneous vertebral augmentation for osteoporotic vertebral compression fractures
Benqiang TANG ; Yanhui WANG ; Songjie XU ; Libin CUI ; Xin YUAN ; Yadong LIU ; Xueming CHEN
Chinese Journal of Orthopaedics 2022;42(5):320-330
Percutaneous vertebral augmentation, including percutaneous vertebroplasty and percutaneous kyphoplasty, has been considered as an effective and safe option in treating osteoporotic vertebral compression fractures. The fractured vertebrae were strengthened by the bone cement injected, thus reducing the symptoms related to fracture. Bone cement injected intraoperatively can be divided into extraspinal (leakage) and intraspinal part, depending on its final location. The former may lead to pulmonary embolism, spinal cord or nerve injury, or some other sequelae; the latter may closely relate to the clinical outcome, radiological outcomes, surgical complications and biomechanical properties. To date, there were a large number of studies on term of the distribution type of bone cement. However, the classification criteria varied and there was lack of literature review on this issue. According to the literature reviewed, the distribution type of bone cement was a critical parameter in percutaneous vertebral augmentation; most classification systems were based on the postoperative X-ray, some based on the postoperative CT, and only a few based on postoperative MRI; in different classification systems, criteria on bone cement morphology tends to be consistent, however, criteria on bone cement range tends to be inconsistent, consistency, similarity and controversy all exited among conclusions between various studies on the morphology and range of bone cement; any single classification system can not describe the distribution of bone cement thoroughly. In this study, classification systems were reviewed, clinical significance and biomechanical conclusions of different classification systems were documented, and the reliability and limitations of classification systems were summarized, hence providing an insight for further research on classifications of the bone cement distribution.
10.Risk factors for cement leakage in percutaneous vertebroplasty for Kümmell disease
Benqiang TANG ; Xueming CHEN ; Libin CUI ; Xin YUAN ; Yadong LIU ; Yongjie WANG
Chinese Journal of Orthopaedics 2020;40(23):1592-1600
Objective:To identify risk factors for cement leakage in percutaneous vertebroplasty (PVP) for Kümmell disease.Methods:A total of 309 patients (351 levels) with Kümmell disease who underwent PVP between November 2015 and June 2019 were retrospectively reviewed. Age, gender, time of symptom onset, staging of Kümmell disease, fracture site(thoracic, lumbar), cortical disruption, type of fracture (wedge, biconcave, crush), fracture severity (mild, moderate, severe), intrusion of posterior wall, basivertebral foramen, puncture approach (unilateral, bilateral), cement distribution pattern (lumped, spongy), cement volume, cement leakage (yes, no) and cement leakage type were recorded. Cement leakage was classified into three types: through the basivertebral vein, through the cortical defect, and through the segmental vein. The data was analyzed by univariate and multivariate analysis to determine related factors of cement leakage in general and each type.Results:The rate of overall leakage was 65.8% (231/351). The leakage rate of basivertebral vein type, cortical defect type, and segmental vein type was 21.4% (75/351), 37.6% (132/351) and 22.8% (80/351), respectively. Multivariate analysis showed that three significant factors related to leakage in general were cortical disruption, basivertebral foramen and cement distribution pattern. Significant factors related to basivertebral vein type leakage were basivertebral foramen and cement distribution pattern. Significant factors related to cortical defect type leakage were cortical disruption and cement distribution pattern. Significant factors related to segmental vein type leakage were basivertebral foramen, cement distribution pattern, cement volume and fracture site.Conclusion:Risk factors of cement leakage in PVP for Kümmell disease include cortical disruption, basivertebral foramen and cement distribution pattern.


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