Efficacy and safety of Tofacitinib in treating the elderly rheumatoid arthritis / 中华老年医学杂志

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.

The clinical significance of the transforming growth factor-β receptor I expression in na?ve CD4 + T cells from patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the clinical significance of the transforming growth factor-β receptor I (TGF-βRⅠ) expression in na?ve CD4 + T cells from patients with systemic lupus erythematosus (SLE). Methods:Na?ve CD4 + T cells were purified using magnetic microbeads from peripheral blood mononuclear cells of SLE patients and healthy controls. Real-time quantitative PCR was used to detect TGF-βRⅠ mRNA level, and flow cytometry was used to detect the percentage of CD69 +CD4 + T cells. Data were analyzed by t test and Pearson correlation analysis. Results:The level of TGF-βR Ⅰ mRNA in na?ve CD4 + T cells from SLE patients was significantly lower than that in healthy controls [(0.674±0.873) vs (1.445±1.112), t=2.301, P<0.05]. The TGF-βR Ⅰ mRNA level was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI) ( r=-0.376, P<0.05), erythrocyte sedimentation rate (ESR) ( r=-0.376, P<0.05), serum creatinine ( r=-0.323, P<0.05) and 24 h urine protein ( r=-0.331, P<0.05), and positively correlated with serum com-plement C3 ( r=0.528, P<0.01). The level of TGF-βRⅠ mRNA level in na?ve CD4 + T cells in SLE patients with renal involvement was lower than that in SLE patients without renal involvement [(0.525±0.536) vs (1.071±1.007), t=2.198, P<0.05]. The TGF-βR Ⅰ mRNA level in the na?ve CD4 + T cells in anti-dsDNA antibody positive group was lower than that in the anti-dsDNA antibody negative group [(0.344±0.315) vs (0.958±1.076), t=2.277, P<0.05]. The expression of TGF-βRⅠ mRNA in na?ve CD4 + T cells from SLE patients was reduced after 24 h stimulation with anti-CD3/CD28 beads [(0.047±0.013) vs (1.008±0.129), t=14.38, P<0.01], which was partially reversed by dexamethasone treatment [(0.240±0.042) vs (0.047±0.013), t=7.845, P<0.01]. Meanwhile, dexamethasone significantly decreased the expression of CD69 in CD4 + T cells [(15.0±2.1)% vs(34.9±2.0)%, t=32.57, P<0.01]. Conclusion:The abnormally low expression of TGF-βRⅠ in na?ve CD4 + T cells may be involved in the pathogenesis of SLE. Glucocorticoid treatment can upregulate the expression of TGF-βRI and inhibit the activation of T cells, This suggests suggesting that TGF-βRⅠ may be a potential target for SLE treatment.

Clinical characteristics of refractory thrombocytopenia secondary to systemic lupus erythematosus / 中华风湿病学杂志

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.

Baseline red blood cell distribution width predicts the response of primary biliary choleitis to ursodeoxycholic acid / 中华风湿病学杂志

Objective To evaluate the value of baseline erythrocyte distribution width (RDW) in evaluating the response to Ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). Methods A retrospective study of 67 patients with PBC who had been treated with UDCA for more than 1 year was conducted. Baseline data and follow-up data after one year treatment were collected. The UDCA response was evaluated by the Paris-Ⅰ standard. According to whether the RDW value was higher than the normal upper limit (15％), patients were divided into two groups:the RDW elevation group and normal RDW group. The clinical and laboratory characteristics were compared. All data were analyzed by t-test, x2 test, Mann-Whitney test,Pearson and Spearman rank correlation analysis. Results Among the 67 PBC patients, 28 cases had elevated RDW and 39 cases had normal RDW. Compared to the non elevated RDW group, the RDW elevation group had significantly higher baseline levels of total serum bilirubin, alkaline phosphatase, glutamic pyruvic transaminase, glutamic pyruvic aminotransferase, Mayo risk score but lower biochemical response rate. RDW levels were positively correlated with TBIL, ALP, GGT and ALT, AST levels, r values were 0.298, 0.609, 0.371 and 0.348, 0.508 (P<0.05) respectively. Conclusion At baseline, patients with higher RDW levels have more abnormal biochemical abnormalities, the Mayo risk score is worse, and the biochemical response rate is lower when compared with patients with normal RDW.

Elevation of red cell distribution width during hospitalization predicts mortality in patients with sepsis / 中华危重病急救医学

Objective To investigate the association of red cell distribution width (RDW) with prognosis in patients with sepsis. Methods Patients with sepsis admitted to intensive care unit (ICU) of the First Hospital of Soochow University from January 2011 to December 2016 were enrolled. All clinical data were collected for participants, which mainly included basic data, main underlying disease, site of infection, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ ) score, blood routine test, biochemical test, blood gas analysis, coagulation index, procalcitonin (PCT), hospitalization days, and 28-day and 90-day mortality. Patients were divided into two groups according to whether the RDW levels were higher than the time of admission or not. Kaplan-Meier survival curve was performed to analyze 28-day and 90-day cumulative survival rates in two groups. Multivariate Cox regression analysis was done to find the independent risk factors of death in patients with sepsis. Results 196 septic patients were eligible to participate into this study. 150 patients (53.57%) had higher RDW levels than those at the time of admission. Compared to negative or static change of RDW group, positive change of RDW group had higher APACHE Ⅱ score (20.42±6.29 vs. 16.17±6.37), more percentage of chronic kidney insufficiency (35.24% vs. 19.78%), bloodstream infection (32.38% vs. 15.38%), continuous renal replacement therapy (CRRT: 32.38% vs. 16.48%), higher level of C-reactive protein [CRP (mg/L): 14.71±3.52 vs. 11.15±7.94], and higher serum creatinine [SCr (μmol/L): 128.0 (74.0, 263.5) vs. 90.0 (57.0, 145.5)], PCT [μg/L: 3.45 (2.39, 6.64) vs. 2.35 (0.56, 3.54)], and lactic acid [Lac (mmol/L): 3.40±1.72 vs. 2.70±1.61]; and had lower levels of hematocrit (Hct: 0.357±0.128 vs. 0.437±0.143), hemoglobin [Hb (g/L):103.60±22.63 vs. 115.67±28.49], platelets [PLT (×109/L): 133.37±87.29 vs. 191.43±87.65], albumin [Alb (g/L):28.15±5.72 vs. 35.51±5.91], total cholesterol [TC (mmol/L): 2.43±1.12 vs. 3.05±1.55], estimated glomerular filtration rate [eGFR (mL·min-1·1.73 m-2): 82.02±63.90 vs. 125.46±83.47], and oxygenation index [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 229.69±60.61 vs. 264.21±74.78]; and longer time of hospitalization [days: 17.0 (12.0, 21.7) vs. 11.0 (7.0, 18.0)], higher 28-day and 90-day mortality (57.14% vs. 36.26%, 62.86% vs. 47.25%) with statistically significant differences (all P < 0.05). It was shown by Kaplan-Meier survival curve that the 28-day and 90-day cumulative survival rate in positive change of RDW group was significantly lower than that of negative or static change of RDW group (χ 12 = 8.462, χ22 = 6.411, both P < 0.05). It was shown by multivariate Cox regression that high APACHE Ⅱ score [odds ratio (OR) = 1.049, 95% confidence interval (95%CI) = 1.010-1.090, P = 0.013] and positive change of RDW (OR = 0.517, 95%CI = 0.280-0.953, P = 0.034) were the risk factors of death in patients with sepsis. Conclusions The change of RDW values during hospitalization was related to the poor outcomes in patients with sepsis. The increase of RDW predicts the progress of sepsis and bad prognosis. Serial surveillance of RDW values could provide useful information for long-term prognosis in sepsis.

Relationship of distortion product in cochlea with cochlear activity revealed by laser interferometry / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the relationship of distortion product in cochlea with cochlear activity and hearing.@*METHOD@#Time variances of distortion product of basilar membrane vibration in vitro guineapig cochlea were observed by laser interferometry.@*RESULT@#Within half hour after a cochlea was isolated from a guineapig, distortion product accompanied with two-tone inhibition in cochlea, can be observed. As time passed, distortion product and two-tone inhibition effect disappeared at the same time. After that, the membrane contiune vibrating in response to the sound stimulus, but the vibration amplitude decreased obviously and continued decreasing until it disappeared completely.@*CONCLUSION@#Distortion product in cochlea is a symbol of cochlear activity which makes the membrane respond in large amplitude vibration to sound stimulus and exhibit two-tone inhibition. The former makes the hearing highly sensitive to sound stimulus, the later makes the hearing perform information abstract well.

The role and significance of serum B factor in the pathogenesis of systemic lupus erythematosus / 中国医师杂志

Objective To investigate the expression of serum B factor in the peripheral blood of patients with systemic lupus erythematosus (SLE),and explore its role in the pathogenesis.Methods Seventy eight patients with SLE in our hospital and 46 healthy persons were eligible to participate in this study.Rate nphelometyr was used to test serum B factor for 78 patients with SLE and 46 healthy controls.According to systemic lupus erythematosus disease activity index (SLEDAI),participants were divided into steady SLE group (SLEDAI ＜ 5) and active SLE group (SLEDAI ≥5),which was further divided into mild,moderate,and serious subgroups.The differences in serum B factor between SLE patients and healthy controls,including SLE patients with different severity,were all compared.Then we analyzed the differences in serum B factor and other laboratory and clinical indexes between active and steady SLE patients.The correction of serum B factor and other laboratory and clinical indexes were also analyzed.Results Compared to healthy controls,patients with SLE had significantly lower value of serum B factor [(27.13 ± 8.98) mg/dl vs (36.73 ± 5.47) mg/dl,t =7.4,P ＜ 0.01].Compared to steady SLE group,SLE active group had significantly lower level of serum factor B,C3 and C4,and also had significant higher level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (all P ＜ 0.05).Moreover,There were significant differences in the lower level of serum B factor between subgroups.Correlation analysis showed that the level of serum B factor was negatively associated with the levels of CRP and SLEDAI scores,whereas serum B factor was positively associated with the levels of C3 and C4 (all P ＜ 0.05).Conclusions Serum B factor is related to SLE.Serum B factor might be involved in the pathogenesis of SLE.Detection of serum B factor is helpful for diagnosis and evaluation of SLE disease activity.

Correlation between serum adiponectin concentration and hyperuricemia on Han in Hunan / 中华风湿病学杂志

Objective To explore the relationship between serum adiponectin concentration and hyperuricemia in Han people in Hunan.Methods Cluster random sampling method was used to carry out the survey during October to December 2008 in Changsha Health Checkup Center of the Second Xiangya Hospital.All subjects completed the questionnaires,physical examination,biochemical measurements,and the data were analyzed by t test,Pearson's correlation analysis and multiple linear regression analysis.Results The Age,WC,TG,SBP,DBP,SUA,BMI were significantly higher in hyperuricemia group compared with the normal uric acid group.The concentration of adiponectin in hyperuricemia group was significantly lower than that in the normal uric acid group (5.0±2.7 vs 6.8±4.2 μg/ml,t=3.961,P＜0.05).In the normal serum uric acid group,the serum adiponectin concentration in female was significantly higher than that in male (t=4.99,P＜0.05).Pearson's correlation analysis showed that serum adiponectin concentration was negatively correlated with the serum uric acid level,but the adiponectin level was not significantly correlated with Age and blood pressure.Stepwise analysis showed that the main factors that could affect the adiponectin level were SUA,gender and BMI (P＜0.05).Conclusion The decreasing of serum adiponectin concentration might be one of the mechanisms of hyperuricemia,therefore,detecting serum adiponectin concentration may provide the basis for the prevention and treatment of hyperuricemia.

Epidemiological study on metabolic syndrome in elderly people in Changsha city / 中国医师杂志

Objective To assess the prevalence of metabolic syndrome (MS) and explore the associated risk factors with MS among 35 ～ 80 years elderly people in Changsha.Methods The survey used by cluster random sampling method (from October to December,2008 ) was carried out by the Physical Examination Center of the Second Xiangya Hospital,Changsha.All subjects aged from 35 to 80 years old had the questionnaires,physical examination,and biochemical measurements.MS was defined by IDF 2005.Results The prevalence of MS was 24.3％ among elderly people in Changsha.The prevalence of MS in male and female was 27.9％ and 19.3％,respectively; which in male was significantly higher than in females ( P ＜0.01).According to census of 2000 in Changsha,the age-adjusted rate of MS was 24.4％ among elderly people,27.8％ in male and 21.9％ in female,respectively.The metabolic abnormalities and the prevalence rate of MS were different in gender and age.Except the essential component of the central obesity in the 194 cases of MS patients,there are 80 cases include other two kinds of metabolic abnormalities,accounting for 41.2％,most of them with elevated blood pressure + sugar metabolism disorders; the most common three kinds of metabolic abnormalities of the 78 cases,accounting for 40.2％ of the people with MS,most of them with high TG + elevated blood pressure + sugar metabolism disorders; With 4 kinds of metabolic abnormalities of 36 patients,accounting for 18.6％ of the MS patients.Increasing age,male,overweight and (or) obesity,high LDL-C hematic disease,high uric acid hematic disease,diabetes were all the risk factors of the elderly people in Changsha city.Conclusions Elderly people in Changsha have a relatively high prevalence of MS,especially for male.The prevalence of MS is considerably high in Changsha,which may continue to rising with the social economic development and population aging.There is an urgent need to take actions to reduce the burden of MS.

Mechanical Noise Enhances Signal Transmission in the Bullfrog Sacculus / 听力学及言语疾病杂志

Objective To study whether mechanical noise acting on the sacculus could enhance the SNR of the 8th nerve’s response.Methods Driving PZT by adding white noise of various level to periodic signals(f=100 Hz),the directly mechanical stimuli was give to the five sacculus submerged in a solution containing perilymph-like, and the afferent activity the 8th nerve was recorded.Results The SNR of the nerve signal was improved by addition nanometer-level noise to the periodic stimuli in all responsive animal(4.1 dB, on average).It was found that 2.3 nm of mechanical noise enhanced the response of the saccular nerve.Conclusion The addition of a few nanometers of noise to a periodic stimuli leads to a substantial improvement in the SNR of the nerve’s response.