1.The expression of System Xc-/ GSH / GPX4 ferroptosis pathway in peripheral blood mononuclear cells of rheumatoid arthritis patients and its effect on the secretion of inflammatory factors
Can Liu ; Wukai Ma ; Changming Chen ; Yang An ; Zong Jiang ; Hai Huang
Acta Universitatis Medicinalis Anhui 2024;59(1):64-70
Objective :
To investigate the expression of genes and proteins in the peripheral blood mononuclear cell ( PBMC) cystine / glutamate antiporter system (System Xc-) / glutathione ( GSH) / glutathione peroxidase 4 ( GPX4) ferroptosis pathway and its influence on inflammatory factors in patients with rheumatoid arthritis ( RA) .
Methods :
30 patients with RA and 30 healthy participants were enrolled.PBMCs were isolated using Ficoll-hypaque density gradient centrifugation.The cells were categorized into the healthy control,RA,ferroptosis inhibitor,ferroptosis in- ducer group.The cell viability was checked using the cell counting kit-8 ( CCK-8) method.Intracellular Fe2 + rela- tive fluorescence intensity and reactive oxygen species (ROS) levels were detected using the FerroOrange and Di- hydroethidium (DHE) fluorescent probes,respectively.Western blot and real-time quantitative PCR (qPCR) de- tected the expression of nuclear factor erythroid 2-related factor 2 ( Nrf2 ) ,solute carrier family 7 member 11 (SLC7A11) ,GPX4 proteins and mRNA.And the flow cytometry quantified the levels of tumor necrosis factor α (TNF-α) ,Interleukin (IL) -1,and IL-6 in the supernatant of each cell group.
Results :
Compared to the healthy control group,the RA group showed a significantly increased Fe2 + concentration and elevated ROS levels,reduced expression of Nrf2,SLC7A11 and GPX4 proteins and mRNA,and increased contents of TNF-α , IL-1 and IL-6 in PBMC supernatant,and the differences were statistically significant.The concentration of Fe2 + and ROS levels in the inhibitor group were lower than those in the RA group,the proteins expressions of Nrf2,SLC7A11 and GPX4 increased,the mRNA expressions of SLC7A11 and GPX4 increased,the content of IL-6 in the PBMC supernatant decreased but the content of TNF-α increased,and the differences were statistically significant.In contrast,the in- ducer group,when compared to the RA group,displayed increased ROS levels,reduced expression of SLC7A11 protein and mRNA and decreased expression of Nrf2 protein,and the contents of TNF-α and IL-1 in the PBMC su- pernatant increased,but the expression of GPX4 protein increased ,and the differences were statistically signifi- cant.The inducer group,compared to the RA group,showed increased cell viability,and the difference was statis-
tically significant (P<0. 000 1) .
Conclusion
The presence of ferroptosis in PBMC in RA patients,inhibiting or inducing PBMC ferroptosis in RA patients,will inhibit or promote the secretion of inflammatory factors.Inhibition of PBMC ferroptosis in RA patients may be helpful in the treatment of RA.
2.Baicalein Attenuates Severe Polymicrobial Sepsis via Alleviating Immune Dysfunction of T Lymphocytes and Inflammation.
Hai-Yan CHEN ; Shu ZHANG ; Jun LI ; Na HUANG ; Jin SUN ; Bao-Hua LI ; Jun YANG ; Zong-Fang LI
Chinese journal of integrative medicine 2022;28(8):711-718
OBJECTIVE:
To investigate the effect of baicalein on polymicrobial sepsis-induced immune dysfunction and organ injury.
METHODS:
A sepsis model was induced in Sprague-Dawley rats via caecal ligation and puncture (CLP). Specific pathogen free rats were randomly divided into a sham group, CLP group and CLP + baicalein (Bai) group (n=16 each). Rats in the CLP + Bai group were intravenously injected with baicalein (20 mg/kg) at 1 and 10 h after CLP. Survival rate, bacterial load, and organ damage were assessed. Then each group was evaluated at 6, 12, and 24 h to investigate the effect of baicalein on immune cells and inflammatory cytokines in septic rats.
RESULTS:
Baicalein treatment significantly improved the survival of septic rats, decreased the bacterial burden, and moderated tissue damage (spleen, liver, and lung), as observed by haematoxylin and eosin staining. Septic rats treated with baicalein had strikingly increased proportions of CD3+CD4+ T cells and ratios of CD4+/CD8+ T cells in the peripheral blood and spleen (all P<0.05). Moreover, baicalein treatment decreased the apoptotic rate of whole white blood cells and spleen cells at 24 h after surgery (P<0.05). Baicalein significantly reduced the levels of tumor necrosis factor α and interleukin-6 (IL-6) and increased IL-10, and the expression levels of galectin 9 were also raised in the spleen (P<0.01).
CONCLUSION
Baicalein may be an effective immunomodulator that attenuates overwhelming inflammatory responses in severe abdominal sepsis.
Animals
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CD8-Positive T-Lymphocytes
;
Flavanones
;
Inflammation/drug therapy*
;
Rats
;
Rats, Sprague-Dawley
;
Sepsis/drug therapy*
3. Clinical Observation of Jiawei Bushen Huoxuetang Combined with Fumigation of Traditional Chinese Medicine After Operation of Vertebral Compression Fracture
Hai-ling ZHAO ; Zong-bo ZHOU ; Jian-qiang LI ; Jian HUANG ; Yi CHENG ; Zhi-fu LU
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(8):95-100
Objective: To observe the effect of Jiawei Bushen Huoxuetang on osteoporotic vertebral compression fractures (OVCF), bone density and bone metabolism. Method: One hundred and sixteen patients with OVCF operation were randomly divided into control group (58 cases) and observation group (58 cases) by random number table. Patients in control group got Alendronate sodium tablets, 70 mg/time, 1 time/week. Menatetrenone soft capsules, 15 mg/time, 3 times/days after meals. Calcium carbonate D3 chewable tablets (Ⅱ), 1 tablet/time, 2 times/days. Based on the treatment in control group, patients in observation group received additional Jiawei Bushen Huoxue decoction, 1 dose/day. The course of treatment was 24 weeks in both groups. The treatment of traditional Chinese medicine(TCM) fumigation was used in combination with the TCM for 2 weeks. At the 4th, 8th, 12th and 24th weeks after treatment, pain degree of waist and back were evaluated by pain visual analogue scale (VAS), and waist dysfunction was evaluated by Oswestry disability index (ODI). Before and after treatment, anterior vertebral height (AVBH), Cobb, femoral neck, lumbar spine bone mineral density and Chinese osteoporosis quality of life scale were evaluated. Before and after treatment, levels of carboxy terminal propeptide of type I collagen (CICP), C-terminal cross-linking peptide of type I collagen (CTX-I), tartrate resistant acid phosphatase (TRACP), bone alkaline phosphatase (BALP) and bone glaprotein(BGP) were detected. Result:By rank sum test, the clinical efficacy in observation was better than that in control group (Z=2.026, P<0.05). At the 4th, 8th, 12th and 24th weeks after treatment, scores of lumbago and back pain VAS and ODI were lower than those in control group (P<0.01). AVBH, femoral neck bone mineral density, and lumbar spine bone mineral density in observation group were higher than those in control group (P<0.01). Cobb angle was smaller than that in control group; and the four dimension scores of COQOL were lower than those in control group (P<0.01). Levels of BALP, CICP, CTX-I and TRACP in observation group were lower than those in control group (P<0.01), and BGP was higher than that in control group (P<0.01). Conclusion:Jiawei Bushen Huoxuetang can enhance bone mineral density, regulate bone metabolism, reduce back pain, promote healing of fracture, and ameliorate osteoporosis, with obvious clinical efficacy.
4. Clinical Observation of Addition and Subtraction Therapy and External Washing Treatment of Danggui Niantongtang to Knee Osteoarthritis with Heumatism Heat Bi Syndrome
Hai-ling ZHAO ; Zong-bo ZHOU ; Jian-qiang LI ; Jian HUANG ; Yi CHENG ; Zhi-fu LU
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(13):105-110
Objective:To observe the short-term clinical efficacy of addition and subtraction therapy and external washing treatment of Danggui Niantongtang to knee osteoarthritis (KOA) with heumatism heat Bi syndrome and to investigate its effect on disease activity. Method:One hundred and eighteen patients with KOA were randomly divided into control group (58 cases) and observation group (60 cases) by random number table. Patients in control group got celecoxib capsules, 0.2 g/time, 1 time/day, diclofenac diethylamine emulgel for the pain, 3 times/days. Patients in observation group got addition and subtraction therapy and external washing treatment of Danggui Niantongtang. The course of treatment was 2 weeks in both groups. Before treatment and at the 2th, 4th, 6th and 14th weeks after treatment, scores of visual analog scale (VAS) were graded for pain in walking and tranquillization. Function of knee joint was evaluated by western Ontario and McMaster university osteoarthritis index (WOMAC) both before and after treatment. Scores of heumatism heat Bi syndrome and Japanese Orthopaedic Associate (JOA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), superoxide dismutase (SOD), interleukin-1β (IL-1β), interleukin-6, tumor necrosis factor-α (TNF-α) and matrix metalloproteinases-3 (MMP-3) levels were evaluated. Result:At the 6th and 14th weeks after treatment, scores of VAS in observation group were lower than those in control group during walking and tranquillization time. Scores of three dimensions in WOMAC (pain, stiffness, joint function) and the total score of WOMAC in observation group were all lower than those in control group (P<0.01). The score of main symptoms of heumatism heat Bi syndrome and the total score in observation group were lower than those in control group (P<0.01). After treatment, levels of ESR, CRP, IL-1β, IL-6, TNF-α and MMP-3 were lower than those in control group, and level of SOD was higher than that in control group (P<0.01). Conclusion:Addition and subtraction therapy and external washing treatment of Danggui Niantongtang can relieve the pain and degree of disease caused by KOA with heumatism heat Bi syndrome, swelling and dysfunction, and can control acute inflammation index, reduce disease activity.
5.Expression of MiR101 and EZH2 in Patients with Mantle Cell Lymphoma and Its Clinical Significance.
Yan-Ling LIN ; Zong-Kai ZOU ; Hai-Yan SU ; Yi-Qun HUANG
Journal of Experimental Hematology 2019;27(3):820-826
OBJECTIVE:
To investigate the expression of miR-101 and EZH2 in patients with mantle cell lymphoma(MCL) and to analyze its correlation with clinical prognosis of MCL patients.
METHODS:
RQ-PCR and S-P immunohistochemistry were used to detect the expressions of miR-101 and EZH2 in tissue of MCL patients. CCK-8 was used to assay the effect of miR-100 minics on the proliferation of Jeko-1 and Mino cells; the flow cytometry with Annexin V/PI double staining was used to assay the apoptosis; Western blot was used to assay the effect of miR-101 minics on the expression of EZH2 protein in Jeko-1 and Mino cells.
RESULTS:
Compared with control group, miR-101 lowly expressed, and EZH2 protein highly expressed in MCL group, with very statistically significant difference(P<0.01).There was negative correlation between miR-101 and EZH2 expression(r=-0.638,P<0.05). The expression of miR-101 and EZH2 significantly correlated with B symptoms, International Prognostic Index(IPI) and Ann Arbor stage, respectively. Survival analysis showed that the overall survival(OS) rate of patients with low expression of miR-101 were significantly lower than that of patients with high miR-101 expression (P=0.0014), the OS rate of patients with EZH2 high expression were significantly lower than that of patients with EZH2 low expression (P=0.0093). The miR-100 minics could inhibit the proliferation of Jeko-1 and Mino cells, and increase the apoptotic rate. The expression of EZH2 protein was markedly suppressed by the miR-100 minics.
CONCLUSION
The expression of miR-101 and EZH2 is different in MCL patients with different clinical stage and prognosis. The miR-101 can inhibit the cell proliferation and induce cell apoptosis of mantle cell lymphoma by targeting EZH2.
Apoptosis
;
Cell Proliferation
;
Enhancer of Zeste Homolog 2 Protein
;
genetics
;
Humans
;
Lymphoma, Mantle-Cell
;
genetics
;
MicroRNAs
;
genetics
;
Prognosis
6.Structural changes of gut microbiota after gastric bypass in obese patients with type 2 diabetes.
Min LANG ; Ke-Hong ZHENG ; Song-Hua ZENG ; Yuan YANG ; Liang-Ping WU ; Zong-Hai HUANG
Journal of Southern Medical University 2017;37(10):1337-1344
OBJECTIVETo investigate the structural changes inintestinal flora and metabolic changes in type 2 diabetic patients with obesity(BMI≥40 kg/m)by sequencing the 16S rRNA genes.
METHODSStool samples were collected from 4 diabetic patients before and after gastric bypass surgery for extraction of the total DNA. The diversity of the intestinal flora in the samples was investigated by 16S rRNA sequencing. After surgery, the changes in glucose and lipid metabolism were evaluated in the patients, and the changesin body mass index (BMI) and waist to hip ratio were assessed at 3 month intervals.
RESULTSAfter gastric bypass, the patient's BMI, waist to hip ratio, glucose metabolism and lipid metabolism gradually recovered the normal levels. The proportion of Bacteroidetesis increased and the proportions of Firmicutes and Proteobacteria decreased in the intestinal bacteria after the surgery.
CONCLUSIONGastric bypass surgery can effectively alleviate the condition of obese patients with type 2 diabetes and improve the composition of the intestinal flora.
7.Efficacy of three-dimensional laparoscopic total thyroidectomy combined with central lymph node dissection for thyroid cancer and its effect on inflammatory responses of the patients.
Xue-Wen LIU ; Qiang LI ; Fei CHEN ; Zhi-Chao LI ; Zong-Hai HUANG
Journal of Southern Medical University 2017;37(6):842-846
OBJECTIVETo analyze the effect of three-dimensional (3D) laparoscopic total thyroidectomy combined with central lymph node dissection for thyroid cancer and its effect on the inflammatory response of the patients.
METHODSThe clinical data were analyzed in 90 patients with thyroid cancer undergoing radical thyroidectomy at our hospital between September, 2013 to April, 2016, including 30 receiving 3D laparoscopic surgeries, 30 with 2D laparoscopic surgeries and 30 with open surgeries. The surgical data, postoperative adverse reactions and the impact of the surgeries on the inflammatory responses of the patients were compared among the 3 groups.
RESULTSCompared with the open surgery and 2D laparoscopic surgery, 3D laparoscopic surgery was associated with lowered blood loss during the surgery and a lowered incidence of adverse reactions. The operation time in 3D group was significantly shorter than that in 2D group (P<0.05), but the total hospitalization expenses were similar between the two groups. The postoperative drainage volume did not differ significantly between the 3D group and the other two groups. The postoperative hospital stay, number of lymph nodes dissected, positivity rate of lymph nodes and the inflammatory response showed no significant differences among the 3 groups (P>0.05).
CONCLUSION3D laparoscopic total thyroidectomy combined with central lymph node dissection is safe and effective and reduces intraoperative blood loss and perioperative adverse reactions without significant influence on inflammatory response in patients with thyroid cancer.
8.A short infrapectineal buttress plate fixing posterior column for complex acetabular fractures through Ilioinguinal ap-proach
Hu WANG ; Kun ZHANG ; Xing WEI ; Pengfei WANG ; Yuxuan CONG ; Zong LI ; Yahui FU ; Jinlai LEI ; Binfei ZHANG ; Hai HUANG ; Yan ZHUANG
Chinese Journal of Orthopaedics 2017;37(1):17-23
Objective To evaluate the clinical outcomes of ilioinguinal approach with short infrapectineal buttress plate fixing posterior column for patients with complex acetabular fractures. Methods Data of 29 consecutive patients (male 22, fe?male 7, age range 25-72 years, average age 53 ± 6.3 years) with complex acetabular who had operated by single ilioinguinal ap?proach with infrapectineal buttress plate from September 2008 to August 2012 were retrospectively analyzed. According to Letour?nel?Judet classifications, there were 4 cases of anterior column and posterior hemi?transverse, 11 cases of associated both?column, 4 of T?shaped and 6 with seagull sign. The acetabular fractures model was printed preoperatively by 3D printing technique for sur?gical simulation, open reduction and internal fixation through single ilioinguinal approach with a short infrapectineal plate fixing posterior column, particularly an ox horn shape K?wire sleeve was developed for drilling and screw insertion using flexible screw?driver. Clinical, radiographic, and functional outcomes assessed by the modified Merle d’Aubigné score were collected. Results Two patients were lost to follow?up, including one patient who died at 15 days postoperative because of pulmonary embolism, and the other one who had moved abroad at 12 months postoperative. The remaining 27 (93%) had a mean follow?up of 40 months (range, 24-75 months). The operating time was 180±35.5 min;the time for the fracture union was 3.5±0.9 month;blood loss during the operating was 500±43.9 ml;no case had fracture re?displacement. At the latest follow?up, radiographic grades were excellent in 17, good in 8, poor in 4, including one poor patient who had a total hip arthroplasty (3%) at 35 months after the internal fixation. The average modified Merle d’Aubigné score was 16 (range, 10-18), and categorized as excellent in 12, good in 8, fair in 5, and poor in 2. Three patients had developed deep venous thrombosis of the lower extremities, and one of them died of pulmonary embo?lism 15 days after operation; two cases of deep venous thrombosis of the lower extremity were found 3-4 days after operation. Thrombosis disappeared 6 months after anticoagulant therapy by warfarin. One case who had superficial wound infection after oper?ation was treated by anti?infection and VSD negative pressure, and incision was healed after one month. One case with poor quality of fracture reduction and seagull sign was treated with total hip arthroplasty after 35 months because of traumatic arthritis. The to?tal complication rate was 24%(7/29). Conclusion In the patient with complex acetabular fractures combining posterior column medial displacement, single Ilioinguinal approach with infrapectineal buttress plates could achieve a stable concentric hip joint, and immediate postoperative ambulation can result in reasonable clinical, radiographic, and functional outcomes.
9.Xinfeng capsule for the treatment of rheumatoid arthritis patients with decreased pulmonary function--a randomized controlled clinical trial.
Lei WAN ; Jian LIU ; Chuan-bing HUANG ; Yuan WANG ; Xi CHEN ; Wan-dong ZHANG ; Gui-zhen WANG ; Hai-xia FAN ; Yao GE ; Rui-lian CHEN ; Yun-xiang CAO ; Rui-kai ZONG ; Tian-yang LIU
Chinese journal of integrative medicine 2016;22(3):168-176
OBJECTIVETo determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function.
METHODSThis was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated.
RESULTSPain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01).
CONCLUSIONSXFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.
Adult ; Aged ; Arthritis, Rheumatoid ; blood ; drug therapy ; pathology ; physiopathology ; Blood Sedimentation ; C-Reactive Protein ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Joints ; pathology ; Male ; Middle Aged ; Quality of Life ; Respiratory Function Tests ; Surveys and Questionnaires ; Treatment Outcome
10.Prevalence of Nontraumatic Osteonecrosis of the Femoral Head and its Associated Risk Factors in the Chinese Population: Results from a Nationally Representative Survey.
De-Wei ZHAO ; Mang YU ; Kai HU ; Wei WANG ; Lei YANG ; Ben-Jie WANG ; Xiao-Hong GAO ; Yong-Ming GUO ; Yong-Qing XU ; Yu-Shan WEI ; Si-Miao TIAN ; Fan YANG ; Nan WANG ; Shi-Bo HUANG ; Hui XIE ; Xiao-Wei WEI ; Hai-Shen JIANG ; Yu-Qiang ZANG ; Jun AI ; Yuan-Liang CHEN ; Guang-Hua LEI ; Yu-Jin LI ; Geng TIAN ; Zong-Sheng LI ; Yong CAO ; Li MA
Chinese Medical Journal 2015;128(21):2843-2850
BACKGROUNDNontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population.
METHODSA nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH.
RESULTSNONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH.
CONCLUSIONSOur findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.
Adult ; Age Distribution ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Female ; Femur Head Necrosis ; epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult


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