Cytochrome P-450 CYP2E1 ; metabolism ; Fatty Liver, Alcoholic ; enzymology ; pathology ; Liver ; enzymology

BACKGROUND: Common threewingnut root has the functions of anti-inflammation and immune inhibition, etc., and it has been used at present to treat various autoimmune diseases including rheumatoid arthritis.. Common threewingnut root has complex components, and triptolide is acknowledged as one of the important effective components of common threewingnut root.OBJECTIVE: To establish rat models of type Ⅱ collagen induced arthritis, and observe the effects of triptolide on the contents of interleukin-6,interleukin-10 and tumor necrosis factor alpha (TNF-α) in peripheral serum and synovial fluid.DESIGN: A randomized control animal experiment.SETTING: Department of Integrated Traditional and Western Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: The experiments were carried out in the Tongji Hospital from November 2004 to July 2005. Fifty healthy male Wistar rats of clean degree were purchased from the experimental animal center of Tongji Medical College, Huazhong University of Science and Technology [qualification number of animal [scxk(E)2004-2007]. Triptolide (nobatch number because of temporary production) was bought from Fujian Institute of Medical Sciences, and the purity was above 98.5%.METHODS: ① Ten of the 50 rats were randomly selected as the normal controls, and the others were made into models. Type Ⅱ collagen emulsion was injected intradermally at five points along the back and tail of the rats,0.05 mL for each point, and injected intradermally at two points after 15 days. The rats in the normal control group were treated with saline in the same way. The effects of the model establishment were evaluated according to the scoring standards of arthritis index at 30 days after the first immunity, and the rats scored 6 points or above were taken as successful models and enrolled in the experiments. Twenty successful rat models were randomly divided into arthritis model group (n=10) and triptolide treated group (n=10). ② Triptolide (100 mg/L)was dispensed into parenteral solution with propylene glycol (0.05 in volume fraction), and then intramuscularly injected into hindlimb of rats in the triptolide treated group (0.04 mL/100 g), once every three days for 30 days. The rats in the normal control group were given isovolume saline, and those in the arthritis model group were treated with isovolume propylene glycol (0.05 in volume fraction). ③ The materials were removed at 30 days after administration. The contents of interleukin-6, interleukin-10 and TNF-α in peripheral serum and synovial fluid were detected with enzyme-linked immunosorbant assay(ELISA).MAIN OUTCOME MEASURES: The effects of triptolide on contents of TNF-α, interleukin-6 and interleukin-10 in peripheral serum and synovial fluid were observed.RESULTS: Fifty male Wistar rats of clean degree were selected, 10 were used as normal controls, and 20 of the other 40 rats were successfully made isto models and enrolled in the analysis of results. ① The TNF-α contents in peripheral serum and synovial fluid were the highest in the arthritis model group, and obviously decreased after treatment of triptolide [(35.09±8.82), (15.35±3.56) ng/L; (44.17±8.94), (22.54±4.76) ng/L; P＜ 0.01], which were similar to those in the normal control group (P ＞ 0.05).② The contents of interleukin-6 in peripheral serum and synovial fluid were the highest in the arthritis model group, and were obviously decreased after treatment of triptolide [(76.58 ±6.81), (42.45 ±5.72) rig/L;(88.69±10.56), (48.67±5.97) ng/L; P ＜ 0.01], but did not recover to the levels in the normal control group (P ＜ 0.05). ③ The contents of interleukin-10 in peripheral serum and synovial fluid were the lowest in the arthritis model group, and obviously increased after treatment of triptolide[(17.53±2.07), (21.23±2.91) ng/L; (10.59±2.96), (14.74±1.85) ng/L; P＜ 0.01], which were similar to those in the normal control group (P ＞ 0.05).CONCLUSION: Triptolide can treat arthritis by modulating the contents of cytokines.

Objective: To investigate the roles of N-acetyl-L-cysteine (NAC) against binge drinking-induced fatty liver in mice. Methods: SPF male C57BL/6 mice were randomly divided into 3 groups, i.e. control group, model group, and NAC/ethanol group (n=10). Mice in model and NAC/ethanol groups were exposed to 3 doses of ethanol (6 g/kg bw) to induced fatty liver, while mice in control group received equal volume and equal energy of maltodextrin solution. NAC was administered to mice at 1 h before ethanol exposure (100 mg/kg bw, i.p.). The mice were sacrificed at 6 h after the last ethanol exposure. The liver and epididymal adipose tissues were collected. Histopathological examination and biochemical assay kit were used to evaluate the fat accumulation, while Western-blot was performed to detect the protein levels of some key factors involved in fat metabolism in liver and adipose tissues. Results: Compored with control group mice, the liver index and liver weight were significantly increased compared with model group, the liver index and TG level in NAC/ethanol group mice were all significantly decreased (P<0.05). Histological examination showed NAC effectively suppressed binge drinking-induced fat accumulation in mice liver. In addition, NAC had no significant effects on the protein levels of peroxisome proliferator-activated receptor-α (PPAR-α), Acy-CoA oxidase (ACOX), sterol regulatory element binding protein 1 c (SREBP-1c) and fatty acid synthase (FAS). Furthermore, the protein levels of hormone sensitive lipase (HSL) did not significantly differ among 3 groups, whereas NAC prevented binge drinking-induced increase of HSL phosphorylation at ser563 and ser660. Conclusion NAC could effectively attenuate binge drinking-induced fatty liver, which might be associated with the inhibition of lipid mobilization by suppressing the phosphorylation of HSL.

The expression and activity of NF-κB in the synovium of collagen-induced arthritis (CIA)rats was detected in order to investigate the possible therapeutic effects of triptolide on rheumatoid arthritis (RA). The experimental Wistar rat model of CIA was set up by intradermal injection of emulsion of bovine collagen Ⅱ and the successful rate of setting-up models was evaluated by arthritis index (AI). Rats were grouped randomly into three groups: normal, model and treatment group.The expression of TNF-α and IL-6 in synovial fluid was detected by ELISA, and the expression and activity of NF-κB in synovium by immunohistochemistry method and by electrophoretic mobility shift assay (EMSA) respectively. As compared with normal group, the expression of TNF-α and IL-6 in synovia (P＜0.05), and the expression and activity of NF-κB (P＜0.05) in synovium were increased in model group. There was statistical difference in above-mentioned indexes between model group and treatment group. Triptolide may play a protective role in RA via downregulating the expression and activity of NF-κB in synovium.

OBJECTIVE: To raise clinical awareness of carcinoembryonic antigen(CEA) increased as initial manifestation of medullary thyroid cancer(MTC) and explore the diagnosis and treatment. METHOD: Clinical data of 2 cases CEA increased as the initial presentation of MTC were retrospectively analyzed and clinical manifestations of the disease, diagnosis, treatment were also discussed by literature reviewing. RESULT: Two patients received thyroid ipsilateral lobe total resection, MTC was confirmed by intraoperative frozen pathology, re-total resection of the contralateral lobe and bilateral VI lymph node dissection were performed. Lymph nodes had no metastasis confirmed by pathological frozen examination. CEA returned to normal within 2 months after surgery. No tumor recurrence and metastasis were found after follow-up for 3 to 24 months. CONCLUSION CEA increased as the initial presentation MTC was rare and clinical identification of CEA increased disease should be taken into account the MTC as possible. Total thyroidectomy and bilateral VI lymph node dissection was the main surgical treatment for it.
Adult ; Carcinoembryonic Antigen ; metabolism ; Carcinoma, Neuroendocrine ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Thyroid Neoplasms ; metabolism ; pathology

Objective:To explore the clinical characteristics and influencing factors of refractory lupus thrombocytopenia (RLTP) secondary to systemic lupus erythematosus (SLE).Methods:A retrospective analysis of 113 patients with thrombocytopenia secondary to SLE in the outpatient and inpatient Department of Rheumatology of the First Affiliated Hospital of Soochow University from January 2015 to June 2018 was carried out. The medical record and laboratory tests of patients were collected, and they were divided them into the refractory group (RLTP, n=25) and non-refractory group (NRLTP, n=88). The clinical manifestations, blood count, biochemical and immunological test of the two groups were analyzed and compared. All data were analyzed by t-test, Mann-Whitney test, χ2 test, Logistic regression analysis and Kaplan-Meier survival analysis. Results:Compared with NRLTP patients, RLTP patients had longer disease course [72(30, 120) months vs 38.5 (8.5, 93) months, H=-2.401, P=0.016), nervous system damage (28% vs 7%, χ2=8.58, P=0.016), higher bleeding risk [(4.6±1.7) vs (3.8±1.3), t=2.548, P=0.012] and higher mortality rate (8% vs 0, χ2=7.167, P<0.01). Meanwhile, the positive rate of anti-GPⅠb/Ⅸ in RLTP group was significantly higher than that in NRLTP group (27% vs 4%, χ2= 8.647, P<0.01). Further unconditional multivariate logistic regression analysis showed that anti-GPⅠb/Ⅸ positive was one of the main influencing factors of RLTP. Kaplan-Meier survival curve analysis revealed that the cumulative survival rate of RLTP group was significantly lower than that of NLTP group ( χ2=7.909, P<0.01). Conclusion:RLTP has a long course of disease, prone to nervous system impairment and positive anti-GPⅠb/Ⅸ antibody, and has a high risk of bleeding. It is necessary to identify these patients early, adjust treatment strategies and improve the prognosis of patients.

Objective:To explore the value of ultrasound measuring gastric sinus cross-sectional area (CSA) to guide early individualized enteral nutrition implementation strategies in sepsis patients.Methods:Thirty septic patients admitted to the EICU and comprehensive ICU of The Second Affiliated Hospital of Nanjing University of Chinese Medicine between January 2021 and December 2022 each were included. EICU patients used bedside ultrasound for gastric sinus CSA to guide the implementation of early enteral nutrition in septic patients, and a routine nutritional support strategy was adopted in the integrated ICU. The correlation of CSA and feeding intolerance in patients with septic gastrointestinal dysfunction, the ROC curve and other relevant indicators of gastrointestinal dysfunction gastrointestinal dysfunction score, SOFA score, APACHEⅡ score, intra-abdominal pressure (IAP), serum protein (PA), [albumin (Alb)]. By comparing the indicators related to inflammation, nutritional status and days of ICU stay after different strategies of the two groups, the advantages of different strategies were analyzed.Results:The baseline data of the two groups were balanced and comparable; the incidence of feeding intolerance was significantly higher (36.67%) than the conventional group (10.00%), with aggressive and early individualized treatment, the incidence rate on the third day was only 10.00%, significantly lower than that in the conventional treatment group (40.00%). Treatment up to the 5th day, the related function scores (gastrointestinal dysfunction score, APACHEⅡ score, SOFA score, IAP), nutritional status indicators (5 d hot card reaching the standard rate, PA, Alb) and inflammation indicators (WBC, PCT, hs-CRP) were significantly improved compared with admission, and is better than the conventional treatment group. In addition, the ICU hospital days and the incidence of aspiration were lower in the ultrasound treatment group ( P <0.05). CSA showed favorable correlation with gastrointestinal dysfunction score, APACHEⅡ score, SOFA score, IAP, PA and Alb, correlation coefficients were 0.79、0.60、0.66、0.71、-0.6 and -0.64( P <0.05). The ROC curve for predicting feeding intolerance by CSA showed the AUC was 0.828, 95% CI was 0.737-0.919, its optimal cutoff value for predicted feeding intolerance was 7.835 cm 2, the sensitivity and specificity were 88.20% and 71.80%. Conclusions:Ultrasound measuring CSA can early and effectively found the feeding intolerance in the patients with sepsis , via giving individualized enteral nutrition implementation strategy, significantly improve the organ function score, nutritional status and inflammation index, reduce the ICU hospital days and aspiration, and correlate with the conventional evaluation index, and sensitivity and specificity are high, worthy of the clinical further promotion.

Objective:To observe the efficacy and safety of Tofacitinib in treating elderly rheumatoid arthritis(RA), in order to provide clinical evidence.Methods:In the randomized control trial, a total of 90 elderly RA patients admitted to the Department of Rheumatology of the First Affiliated Hospital of Soochow University from January 2019 to January 2021 were selected and divided into Methotrexate group(MTX group, MTX 10mg, qw, n=45)and Tofacitinib group(TOF group, oral 5mg, bid, n=45). The efficacy and safety of the two groups were evaluated at week 12.The primary endpoint was the proportion of patients meeting the American College of Rheumatology 50%(ACR50)improvement response criteria at week 12.Secondary endpoints included ACR20/70 improvement response, proportion of patients who met treat-to-target(T2T)criteria, including Disease Activity Score in 28 joints using erythrocyte sedimentation rate(DAS28-ESR), Disease Activity Score in 28 joints using C-reactive protein level(DAS28-CRP), clinical disease activity index(CDAI), and simplified disease activity index(SDAI), and patient-reported outcomes(PROs)which included changes compared to baseline in pain visual analog scale(VAS)and Health Assessment Questionnaire Disability Index(HAQ-DI)score, at week 12.Safety outcomes including drug-related adverse events, serious adverse events, dropping out due to adverse events, and deaths were assessed throughout.Results:Five patients in each group withdrew from the trial due to adverse events, and the number of patients who finally completed the observation was 40 in each group.At week 12, the ACR50 response rate was higher in TOF group than in MTX group[35%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018)], achieving the primary endpoint.When comparing TOF vs.MTX group, the ACR20 response rate[55%(22/40) vs.25%(10/40), χ2=7.500, P=0.006]and ACR70 response rate[25%(10/40) vs.7.5%(3/40), χ2=4.501, P=0.034], and proportions of indexes of disease remission including DAS28-ESR<2.6[25%(11/40) vs.7.5%(3/40), χ2=4.501, P=0.034], or DAS28-CRP<2.6[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], or CDAI≤2.8[30%(12/40) vs.10%(4/40), χ2=5.000, P=0.025], or SDAI≤3.3[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], and the proportions of patients with low disease activity including DAS28-ESR≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or DAS28-CRP≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or CDAI≤10[37.5%(15/40) vs.17.5%(7/40), χ2=4.013, P=0.045], or SDAI≤11[37.5%(15/40) vs.15%(6/40), χ2=5.230, P=0.022], as well as changes compared to baseline data in pain VAS[(26.51±8.32)scores vs.(14.16±4.39)scores, t=8.371, P<0.001]and in HAQ-DI score(0.65±0.24 vs.0.32±0.06, t=9.387, P<0.001)were all better in the TOF group than in the MTX group at week 12.During the 12-week observation period, the number of patients with infection and hyperlipidemia was higher in TOF group than in MTX group, while the number of patients with abnormal blood cell count and liver function was lower than that in MTX group, but the differences were not statistically significant(all P<0.05). Conclusions:Tofacitinib has good efficacy and safety in the elderly RA.In patients over 70 years of age who are at high risk of infection, tofacitinib should be used with caution.

BACKGROUND:The incidence of osteoporosis significantly increases in the patients with rheumatoid arthritis,and it remains unclear whether the presence of a large number of immune complexes in serum promotes the onset and development of osteoporosis. OBJECTIVE:To investigate the correlation between serum immune complexes and osteoporosis in patients with rheumatoid arthritis. METHODS:(1)Clinical trial:Serum and clinical data of 50 healthy controls and 50 patients with untreated rheumatoid arthritis were collected and retrospectively analyzed.Total immune complex level in serum was compared between two groups.Correlation of serum total immune complexes with bone mineral density,bone turnover markers and other clinical indicators in patients with rheumatoid arthritis was analyzed.(2)Cell experiment:Peripheral blood mononuclear cells from healthy volunteers were isolated and cultured,and divided into four groups:rheumatoid arthritis group was added with total immune complex suspension from rheumatoid arthritis patients;normal control group was added with total immune complex suspension from healthy medical checkups;positive control group was added with α-MEM medium containing macrophage colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand,and negative control group was added with α-MEM medium.Tartrate-resistant acid phosphatase staining was performed to observe the formation of osteoclasts after 7 days of treatment, RESULTS AND CONCLUSION:(1)Clinical trial:The total immune complex and serum alkaline phosphatase levels in patients with rheumatoid arthritis were significantly higher than those in health controls(P＜0.01,P＜0.05).Pearson correlation analysis showed that serum total immune complex level was positively correlated with erythrocyte sedimentation rate(r=0.330,P=0.019),serum alkaline phosphatase(r=0.545,P=0.001),anti-cyclic citrullinate peptide(r=0.377,P=0.007)and c-terminal telopeptide of type Ⅰ collagen(r=0.738,P=0.001),and negatively correlated with lumbar bone mineral density(r=-0.595,P=0.001)in patients with rheumatoid arthritis.Binary Logistic regression analysis showed that age[odds ratio(OR)=1.086,95%confidence interval(CI)(1.022,1.154),P=0.008],anti-cyclic citrullinate peptide[OR=1.002,95%CI(0.999,1.005),P=0.035],c-terminal telopeptide of type Ⅰ collagen[OR=0.141,95%CI(0.015,8.900),P=0.008]and serum total immune complexes[OR=2.895,95%CI(1.228,6.827),P=0.001]were the influencing factors for abnormal bone mass(reduced bone mass or osteoporosis)in patients with rheumatoid arthritis.(2)Cell experiment:Tartrate-resistant acid phosphatase positive osteoclasts were observed in the positive control group,normal control group and rheumatoid arthritis group,and there were more osteoclasts in the rheumatoid arthritis group than in the normal control group(P＜0.01).To conclude,serum total immune complexes can be used as a potential serologic predictor of rheumatoid arthritis complicated with osteoporosis,and removing immune complexes in serum or interfering with the binding of immune complexes to their receptors may be an effective means for the prevention and treatment of rheumatoid arthritis complicated with osteoporosis.

OBJECTIVETo investigate the preventive effects of garlic oil (GO) on benzene-induced hematotoxicity in mice.

METHODSSpecific pathogen-free male Kunming mice were randomly divided into 5 groups, i.e., control group, model group, and low-, middle-, and high-dose GO groups (n = 20 in each group). Mice in GO groups were orally given GO at 20, 40, or 80 mg/kg BW, while mice in the other two groups received an equal volume of corn oil. Two hours later, mice in model group and GO groups were orally given benzene (20%, v/v, dissolved in corn oil, 10 ml/kg BW) for 21 days consecutively. On the 22nd day, blood was collected from the orbital sinus, to determine the counts of red blood cells (RBC), white blood cells (WBC), and platelets (PLT) and hemoglobin level using an automatic blood cell counter. The mice were sacrificed thereafter. The spleen was excised and weighed for calculation of the spleen index (spleen weight/body weight×100%).

RESULTSThe counts of WBC, RBC, and PLT and Hb level in the model group were reduced by 40%, 18%, 28%, and 23.6%, respectively, as compared with those in the control group (P < 0.01). Compared with those in the model group, WBC and PLT counts in the high-dose GO group increased by 95% and 66%, respectively (P < 0.01), wherein lymphocytes and monocytes increased by 142% and 100%, respectively (P < 0.01); the RBC count and Hb level in the low-dose GO group increased by 15% and 16%, respectively (P < 0.05). GO significantly suppressed benzene-induced decreases in spleen weight and spleen index.

CONCLUSIONGO is capable of suppressing benzene-induced hematotoxicity in mice. One possible mechanism may be promotion of hematopoiesis in the spleen.

Allyl Compounds ; pharmacology ; Animals ; Benzene ; poisoning ; Blood Cell Count ; Disease Models, Animal ; Garlic ; chemistry ; Male ; Mice ; Plant Oils ; pharmacology ; Sulfides ; pharmacology