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.

Objective:To observe the histopathological changes in peripheral retinal lesions under intraoperative optical coherence tomography (iOCT).Methods:A retrospective case series study. Eighty-eight patients (194 eyes) who underwent vitreoretinal surgery in the Department of Ophthalmology at the East Ward of the First Affiliated Hospital of Zhengzhou University from October 2021 to May 2022 in 94 eyes were included in the study. Among them, 49 cases were male and 39 cases were female, with the mean age of (50.93±17.55) years. Ninety-four eyes included 32 eyes with retinal detachment, 6 eyes with proliferative diabetic retinopathy, 28 eyes with vitreous hemorrhage, 8 eyes with ocular trauma, 14 eyes with the macular lesion, 1 eye with uveitis, 1 eye with family exudative vitreoretinopathy (FEVR), 1 eye with acute retinal necrosis (ARN), and 3 eyes with lens dislocation. All affected eyes were examined with iOCT during vitreoretinal surgery. The iOCT scanning of the peripheral retina was performed with the help of episcleral pressure. The pre-equatorial and serrated edge anterior and posterior of retinas were scanned according to the characteristics of different fundus diseases. Various abnormal fundus manifestations were recorded.Results:In 94 eyes, 53 eyes (56.38%, 53/94) have different types of retinopathy in the peripheral retina. Of these, 7 eyes (7.45%) have retinal cystoid degeneration; 19 eyes (20.21%) have lattice degeneration; and 8 eyes (8.51%) have pigment degeneration; 9 eyes (9.57%) have pavement-like degeneration; 7 eyes (7.45%) have small occult holes; 1 eye (1.06%) has familial exudative vitreoretinopathy (FEVR) serrated edge "dyke-like" proliferative degeneration; 4 eyes (4.26%) have vitreous and retinopathy adhesions; and one eye (1.06%) has ARN.Conclusion:With clear refractive media, iOCT can provide clear scans of different peripheral retinal lesions.

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.

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 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.

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.

Objective To investigate effects of polyphylin Ⅰ on the proliferation and apoptosis of human melanoma cell line A375,and to explore their mechanisms.Methods Normal human melanocytes isolated from healthy human foreskin were divided into 6 groups to be treated with 0,1.5,3.0,6.0,9.0,12.0 mg/L polyphyllin Ⅰ respectively.A375 melanoma cells were divided into 4 groups,i.e.,control group,1.5-,3.0-,6.0-mg/L polyphyllin Ⅰ groups,to be treated with 0,1.5,3.0,6.0 mg/L polyphyllin Ⅰ,respectively.Cell counting kit-8 (CCK8) assay was performed to evaluate the effect of polyphyllin Ⅰ on the proliferation of normal human melanocytes and A375 cells.Hoechst 33258 fluorescent staining was conducted to observe the morphology of apoptotic cells,flow cytometry to estimate cell cycle phase distribution and apoptosis rate,dichloro-dihydro-fluorescein diacetate (DCFH-DA) fluorescent probe assay to detect the level of reactive oxygen species (ROS),rhodamine-123 staining to evaluate changes of mitochondrial membrane potential,spectrophotography to detect the level of ATP in A375 cells,as well as levels of lactic acid and glucose in the culture supernatant of A375 cells,and Western blot analysis to determine the protein expression of Bcl-2,Bcl-2-related X protein (Bax),cleaved-caspase-3,cyclin D1 and pyruvate kinase isozyme type M2 (PKM2).Statistical analysis was carried out by using one-way analysis of variance (ANOVA) for comparisons among groups and Student-Newman-Keuls-q (SNK-q) test for multiple comparisons.Results CCK8 assay showed that the treatment with polyphyllin Ⅰ at concentrations of 1.5,3.0,6.0 mg/L for 48 hours had no effects on the proliferation of normal human melanocytes,but significantly inhibited the proliferation of A375 cells.The survival rate of A375 cells was significantly lower in the 1.5-,3.0-,6.0-mg/L polyphyllin Ⅰ groups than in the control group (P ＜ 0.01).After the treatment with polyphyllin Ⅰ,distinct apoptotic morphology of A375 cells was observed under fluorescence microscope.Additionally,along with the increase of polyphyllin Ⅰ concentrations (0,1.5,3.0,6.0 mg/L),there were gradual increasing trends in the apoptosis rate of A375 cells (4.25％ ± 1.27％,10.03％ ± 1.49％,36.62％ ± 1.97％,44.11％ ± 2.47％ respectively,F =665.7,P ＜ 0.01),the percentage of A375 cells at G0/G1 phase (54.13％ ± 2.57％,67.35％ ± 3.79％,74.39％ ± 3.29％,82.29％ ± 3.99％ respectively,F =71.81,P ＜ 0.01),the level of ROS in A375 cells (P ＜ 0.01),the level of glucose in the culture supernatant (P ＜ 0.01),and the protein expression of Bax and cleaved-caspase-3 (both P ＜ 0.01),while gradual decreasing trends were found in the levels of mitochondrial membrane potential and ATP in A375 cells (both P ＜ 0.01),the level of lactic acid in the culture supernatant (P ＜ 0.01),and the protein expression of Cyclin D1,Bcl-2 and PKM2 (all P ＜ 0.01).Conclusion Polyphyllin Ⅰ can effectively induce A375 cell apoptosis by promoting the production of ROS in A375 cells and decreasing the mitochondrial membrane potential,and arrest A375 cells at G0/G1 phase by inhibiting the expression of PKM2 and Cyclin D1.

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.
Acoustic Stimulation ; Animals ; Basilar Membrane ; physiology ; Cochlea ; physiology ; Guinea Pigs ; Hearing ; physiology ; Hearing Tests ; Interferometry ; Sound

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.

10.3969/j.issn.1007-3969.2013.04.011