[Application of cardiac magnetic resonance imaging in subclinical systemic sclerosis primary heart involvement].

Objectives: Primary cardiac involvement (SSc-PHI) in systemic sclerosis is an important prognostic factor. We aimed to characterize and identify subclinical SSc-PHI using cardiovascular MRI to determine whether disease severity and serum biomarkers are associated with subclinical SSc-PHI. Methods: A total of 26 patients with SSc who had no history of cardiovascular disease or pulmonary hypertension underwent 3 T-enhanced cardiovascular MRI. Measurements included native T1, extracellular volume, advanced gadolinium enhancement, T2 mapping, and left ventricular volume function. Troponin T and N telencephalic natriuretic peptide precursors were also determined. Results: LGE was observed in 13 of 26 patients (50.0%), suggesting focal fibrosis, and T2 mapping was significantly higher in the dcSSc group than in the lcSSc group (P=0.009). Left ventricular volume and function were within the normal range in all patients, but final systolic left ventricular volume was significantly higher in dcSSc than in lcSSc (P=0.021). The modified Rodnan skin score (mRSS) was significantly higher in patients with LGE focal fibrosis (P=0.019). Logistic regression analysis confirmed the association between mRSS and LGE (OR=1.224, P=0.037). In multivariate analysis, T2 mapping was negatively correlated with disease course, and was correlated with dcSSc and fingertip ulcer (R2=0.711, P=0.018, P=0.013, P=0.030). Troponin T was correlated with T2 mapping (r=0.555, P=0.049). Conclusions: Subclinical SSc-PHI is characterized by diffuse and focal myocardial fibrosis, but preserves myocardial systolic function. Subclinical SSC-Phi is associated with TNT, SSc disease severity, and complex peripheral vascular disease. These data provide information for identifying individuals at risk of SSc-PHI.

[Efficacy of rituximab therapy for 10 patients suffering from systemic lupus erythematosus with intestinal involvement].

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

[Influencing factors of hypertension and diabetes care cascade: a qualitative study].

Objective: Employing the cascade care model, this qualitative study explores determinants influencing the cascading care stages of hypertension and diabetes by interviewing various stakeholders. Methods: In July 2023, purposive sampling was employed to recruit participants from Gongyi and Wugang cities in Henan Province, and Linqu County in Weifang City, Shandong Province. Semi-structured in-depth interviews were conducted with representatives of policymakers, healthcare institution managers, providers, and patients with hypertension and diabetes.And thematic analysis was performed using both inductive and deductive approaches. Results: A total of 82 individuals were interviewed, with an age range of (53.8±12.0) years, among which 48 (58.5%) were male; including 5 policymakers, 10 institutional managers, 20 healthcare providers, and 47 patients with hypertension and diabetes. The study identified both barriers and facilitating factors at the patient, healthcare provider, and system levels across various stages: awareness, screening, diagnosis, treatment, long-term management, and control of hypertension and diabetes. Conclusion: By delineating and analyzing the barriers and facilitators at each stage of hypertension and diabetes care, this study lays the groundwork for the development of effective, feasible, and sustainable implementation pathways, with significant implications for the enhanced management of hypertension and diabetes in China.

[Efficacy and safety of half-dose rituximab in the treatment of 23 cases with lupus nephritis].

The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) µmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)µmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.

[Analysis of factors associated with proximal junctional kyphosis after surgery for Lenke type 5 adolescent idiopathic scoliosis].

Objective: To investigate the risk factors associated with the development of proximal junctional kyphosis (PJK) after posterior spinal fusion for in children with Lenke type 5 adolescent idiopathic scoliosis (AIS). Methods: It was a retrospective case-control study that included medical records of 98 children with Lenke type 5 AIS who underwent posterior orthopedic surgery under general anesthesia at the Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2013 to December 2018. There were 23 males and 75 females with a mean age of (14.5±2.2) years (10-18 years). Patients were divided into PJK and non-PJK groups according to whether the posterior junctional angle (PJA) was greater than 10° and increased for more than 10° from the preoperative period at the the last follow-up. Univariate analysis was used to analyze the correlation of general data of the children with occurrence of PJK after the operation. Multivariate logistic regression analysis was used to analyze the risk factors of postoperative PJK. Results: There were 35 cases in the PJK group and 63 cases in the non-PJK group. The PJK and non-PJK groups were followed up for (35.6±7.3) months and (36.4±7.5) months, respectively, and the difference was not statistically significant (P=0.637). There was no statistically significant difference between the two groups in general data such as gender, age, and body mass index (all P>0.05), while there were statistically significant differences between the two groups in upper instrumented vertebrea (UIV) location and junctional area posterior ligamentous complex (PLC) injury (all P<0.05). The results of univariate analysis showed that UIV location at T10-T12, junctional area PLC injury, preoperative coronal thoracic curve (TC), preoperative and final follow-up PJA, and preoperative and final follow-up pelvic incidence-lumbarlordosis (PI-LL) were correlated with postoperative PJK (OR=2.50, 5.37, 0.92, 1.12, 1.32, 1.06, 3.35, all P<0.05). Multifactorial logistic regression analysis showed that UIV located at T10-T12 (OR=2.346, 95%CI: 1.582-3.481, P=0.001), junctional area PLC injury (OR=5.112, 95%CI: 1.283-20.418, P=0.023) and last follow-up PI-LL (OR=1.826, 95%CI: 1.558-24.745, P=0.012) were risk factors for the occurrence of postoperative PJK in children with Lenke type 5 AIS. Conclusions: Postoperative UIV fixation to the thoracolumbar segment, PLC injury in the junctional area and excessive postoperative PI-LL in children with Lenke type 5 AIS may be the risk factors for the occurrence of PJK after the operation. It is suggested that avoidance of UIV selection to the thoracolumbar segment, intraoperative protection of the PLC located near the UIV and restoration of a good PI-LL relationship may reduce the incidence of PJK.

[The development of artificial cervical disc replacement from the perspective of orthopedic bionic therapy].

The modern surgical treatment of cervical degenerative disc disease can be traced back to the advent of anterior cervical decompression and fusion.With the emergence of fusion-related complications,different scholars have promoted the gradual transformation of cervical degenerative disc diseases from "fusion fixation" to "non-fusion reconstruction" through in-depth fusion with materials science,engineering mechanics and other disciplines.The innovation of this treatment concept is consistent with the original intention of "structural remodeling,functional reconstruction,maximum repair and reconstruction of the morphology and function of skeletal muscle system" in orthopedic bionic treatment,which is essentially in line with the "bionic alternative therapy" in orthopedic bionic therapy.This paper focuses on the surgical treatment of cervical degenerative disc diseases,reviews the development history of artificial cervical disc replacement,analyzes the evolution from orthopedic biomimetic therapy,and explores a new direction for the design of artificial cervical disc prostheses and the treatment of cervical degenerative disc diseases in the future.

[Predictive value of SYNTAX-â ¡ score on prognosis of patients with chronic total occlusion undergoing percutaneous coronary intervention].

Objective: To investigate the predictive value of SYNTAX-Ⅱ score on long term prognosis of patients diagnosed with chronic total occlusion (CTO) and received percutaneous coronary intervention (PCI). Methods: Patients undergoing CTO-PCI in Fuwai hospital from January 2010 to December 2013 were enrolled in this retrospective analysis. The SYNTAX-Ⅱ score of the patients was calculated. According to SYNTAX-Ⅱ score tertiles, patients were stratified as follows: SYNTAX-Ⅱ≤20, 2027. Primary endpoint was major adverse cardiac events (MACCE), including all-cause death, myocardial infarction, stroke and any revascularization. Secondary endpoints included stent thrombosis, heart failure and target lesion failure (TLF). Patients were followed up by outpatient visit or telephone call at 1 month, 6 months and 1 year after PCI, and annually up to 5 years. Multivariate Cox regression model was used to analyze the independent risk factors of all-cause death in patients undergoing CTO-PCI. The predictive value of SYNTAX score with SYNTAX-Ⅱ score for all-cause death was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: A total of 2 391 patients with CTO and received PCI were enrolled in this study. The mean age was (57.0±10.5) years, 1 994 (83.40%) patients were male. There were 802 patients in lower tertile group (SYNTAX-Ⅱ≤20), 798 patients in intermediate group (2027). At the end of 5-year follow-up, the loss to follow-up rate of the three groups was 9.10%(73/802), 10.78%(86/798)and 8.85%(70/791), respectively. The rate of all-cause mortality (1.78% (13/729) vs. 3.65% (26/712) vs. 9.02% (65/721), P<0.001), cardiac death (1.37% (10/729) vs. 2.11% (15/712) vs. 4.85% (35/721), P<0.001), target vessel myocardial infarctions (4.25% (31/729) vs. 4.49% (32/712) vs. 7.07% (51/721), P=0.03), probable stent thrombosis (1.51% (11/729) vs. 2.81% (20/712) vs. 3.61% (26/721), P=0.04) and heart failure (1.78% (13/729) vs. 1.97% (14/712) vs. 5.41% (39/721), P<0.001) increased in proportion to increasing SYNTAX-Ⅱ score (all P<0.05). Multivariable Cox regression analysis indicated that female (HR=2.05, 95%CI 1.12-3.73, P=0.01), left ventricular ejection fraction (HR=0.97, 95%CI 0.95-1.00, P=0.05) and SYNTAX-Ⅱ score (HR=1.07, 95%CI 1.02-1.11,P=0.01) were independent predictors for all-cause mortality in patients undergoing CTO-PCI. The predicted value of the SYNTAX-Ⅱ score for all-cause death was significantly higher than the SYNTAX score (AUC 0.71 vs. 0.60, P=0.003). Conclusion: For CTO patients who underwent percutaneous coronary intervention, SYNTAX-Ⅱ score is an independent predictor for 5-year all-cause death, and SYNTAX-Ⅱ serves as an important predictor for all-cause death in these patients.

[Epidemiological analysis of non-enterovirus 71 and non-coxsackievirus A16 enterovirus].

Enteroviruses (EV) are the most common pathogens in humans, often causing large-scale infectious diseases, such as: hand, foot and mouth disease, herpes angina, myocarditis, encephalitis, aseptic meningitis, acute flaccidity Paralysis and acute flaccid myelitis and other nervous system and cardiopulmonary diseases, and them often infect children under 5 years old, severely can cause fatal complications. In recent years, the prevalence of non-enteric virus A71 (EV71) and non-coxsackievirus A16 (CV-A16) enteroviruses has gradually increased, and the dominant strains of EVs have gradually changed. A timely grasp of the etiology, epidemiology, and molecular evolution characteristics of EVs is of great significance to the prevention and control of EVs. Therefore, this article reviews the current status of diseases caused by non-EV71 and non-CV-A16 enteroviruses and analysis the molecular epidemiology, in order to have a certain prompting effect on the prevention and control of EVs.

[Advances in researches of serotype 2 novel oral polio vaccine].

In April 2016, the Global Polio Eradication Initiative (GPEI) adjusted its polio vaccination strategy, converting trivalent oral polio vaccine (tOPV) into bivalent oral polio vaccine (bOPV), and withdrawing type 2 oral polio vaccine (OPV2) globally. However, after the withdrawal of OPV2, there were many outbreaks of type-2 circulating vaccine-derived poliovirus (cVDPV2) in Asia and Africa. In order to eradicate poliovirus completely, GPEI launched the research and development of the novel serotype 2 oral polio vaccine (nOPV2) in 2010 and considering whether it is necessary to reuse OPV. This paper summarizes the epidemiological situation of cVDPV2 before and after OPV2's withdrawal, the related factors affecting the reuse of OPV and the related research progress of nOPV2.

[The 478 th case: multiple myalgia with intramuscular nodules].

A 28-year-old man was admitted to the first medical center of Chinese People's Liberation Army General Hospital because of multiple myalgia and intramuscular nodules for more than 2 months. The patient complained of dysphagia, fever and weight loss 2 months ago. Magnetic resonance imaging and biopsy revealed nodular fasciitis. Inflammatory indicators including C-reactive protein, erythrocyte sedimentation rate, platelet count and fibrinogen were slightly elevated. Urine occult blood was positive. Abdominal ultrasound revealed left hydronephrosis. Because nodular fasciitis could not explain the whole situation, a needle biopsy of intramuscular nodules was performed. Pathological examination revealed intramuscular metastatic adenocarcinoma with poor differentiation. Gastric endoscope and positron emission tomography-computed tomography confirmed the diagnosis of advanced gastric adenocarcinoma with extensive metastases of esophagus, lymph nodes, muscles, ureter and bone. Although chemotherapy was given, the patient died of disease progression six months later.

[Clinical observation of single-segment cervical adjacent segment disease treated with artificial cervical disc replacement].

Objective: To investigate the clinical outcomes and radiographic results of artificial cervical disc replacement (ACDR) for cervical adjacent segment disease (ASD). Methods: The clinical data of 28 patients with single-segment cervical ASD treated with ACDR in Xi 'an Honghui Hospital from December 2013 to July 2016 were retrospectively analyzed. There were 19 males and 9 females with a mean age of (46±7) years (36-63 years). Preoperative, postoperative 1 month and postoperative 24 months of clinical and radiographic outcomes were recorded and compared. The clinical outcome mainly includes Japanese orthopedic association (JOA), Neck Disability Index (NDI%), Odom score and complications. Imaging assessment mainly included range of motion (ROM) of cervical spine, surgical segment ROM, Cobb angle of surgical segment, degree of adjacent disc degeneration, heterotopic ossification, and prosthesis related image parameters. Results: In terms of clinical outcome, the average JOA score was 12.7±1.5 before surgery, 14.0±1.0 one month after surgery, 15.8±0.9 24 months after surgery, and the improvement rate of JOA was 75%±19%. The mean NDI% was 27.0%±2.8% before surgery, 20.5%±1.6% one month after surgery, and 15.3%±2.8% 24 months after surgery; the difference before and after treatment was statistically significant (F=159.101, P<0.01). Twenty patients were classified with excellent Odom score and 8 patients with good Odom score at the final follow-up. The total ROM of cervical spine, operation segment ROM, operation segment Cobb angle were all improved significantly after the operation (F=4.633, 6.063, 26.952, all P<0.05). There was a statistical difference in Miyazaki classification between adjacent discs above ACDR and below the fusion segment 24 months after surgery (µ(c)=2.12, P=0.034). The incidence of heterotopic ossification was 14.3%. The results of displacement degree of prosthesis were as follow: coronal plane (0.30±0.11) mm, sagittal plane (0.28±0.10) mm; subsidence of the prosthesis: (0.27±0.09) mm. No prosthesis loosening was observed. Conclusions: The clinical outcome of revision of cervical ASD by ACDR is satisfactory. The risk of intervertebral disc degeneration in adjacent segments is significantly lower than that of ACDF due to the presence of certain motor function postoperatively.

[Study on safety of adjuvant radiotherapy concurrent with weekly chemotherapy for stage â ¡B-â £A esophageal carcinoma after radical resection].

Objective: To evaluate the tolerability and short-term efficacy of chemo-radiotherapy in 125 patients with stage ⅡB-ⅣA esophageal carcinoma after radical resection. Methods: We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo-radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results: 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo-radiotherapy (41.6%), while 73 patients underwent only 1-4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up (6.4%). The 1-year and 3-year overall survival rate were 91.6% and 57.0%, respectively, with a median survival time of 64.4 months. The 1-year and 3-year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo-radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1-2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor (P=0.010). Conclusions: Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB-ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

[The effect of arthroscopic synovectomy on refractory knee arthritis with popliteal cyst in 153 patients].

Objective: To investigate the efficacy of arthroscopic synovectomy on refractory knee arthritis complicated with popliteal cyst. Methods: Patients diagnosed as rheumatoid arthritis (RA) or spondyloarthritis (SpA) with refractory knee arthritis who underwent knee arthroscopic synovectomy in our hospital from 2010 to 2017 were enrolled, including 20 patients (16 RA, 4 SpA) with popliteal cyst. Clinical data, RA disease activity score (DAS28), SpA back pain score, etc, were collected to evaluate the efficacy of knee surgery. Results: Erythrocyte sedimentation rate (ESR) [58(17, 79)mm/1h vs. 19(9, 30)mm/1h, P< 0.001],C reactive protein (CRP) [3.72(0.92,8.14) mg/L vs. 0.85(0.10,3.08) mg/L,P<0.001], rheumatoid factor [64.6(20.2,193.3) vs. 20.5(10.0,58.4),P<0.001], DAS28 score(4.67±1.25 vs. 2.81±1.23,P<0.001), knee joint discomfort score [5(4,6) vs. 2(1,3),P<0.001] and the volume of knee joint effusion by ultrasound (P<0.05) in 95 RA patients were significantly decreased compared to those before operation. ESR [27(12,54)mm/1h vs. 20 (16,28) mm/1 h,P<0.001], CRP [3.27(1.06,6.95) mg/L vs. 1.41(0.34,3.03)mg/L,P<0.001],knee discomfort score [2(0,5) vs. 1(0,3),P<0.05], back pain visual analogue score (VAS) [5(4,5) vs. 2(1,3), P<0.001], and the volume of knee joint effusion by ultrasound (P<0.001) in 58 SpA patients were significantly lower than those before the operation.The rate [16.84%(16/95) vs. 6.32%(6/95),P=0.023] and grading (P=0.007) of popliteal cyst in RA were decreased after the operation. No statistically difference was observed in the rate [6.90% (4/58) vs. 5.17%(3/58), P=0.697] of popliteal cyst in patients with SpA, yet with a trend of decrease in 4 patients. Conclusion: This study provide evidence that knee arthroscopic synovectomy has a good effect for refractory knee arthritis, which can reduce disease activity, improve joint symptoms and decrease the grading of popliteal cyst.

[A survey on the current status and related factors of influenza vaccination among health care workers in tertiary hospitals of Xining city during the influenza epidemic season from 2017 to 2018].

Objective: To evaluate the current status and related factors of influenza vaccination among health care workers (HCWs) in tertiary hospitals of Xining city after the implementation of the free influenza vaccination policy. Methods: In August 2018, the cluster sampling method was used to select four medical institutions in Xining that had previously conducted investigations and interventions. All HCWs(excluding logistic staff) in each medical institution were included in the study. A total of 3 260 valid respondents were included. Questionnaires were used to collect the demographic characteristics, influenza and influenza vaccination awareness, implementation of free policy in the influenza epidemic season from 2017 to 2018, influenza vaccination status, awareness of influenza vaccination schedule and free policy. The multivariate logistic regression model was used to analyze related factors of influenza vaccination. Results: The age of respondents was (31.41±5.00) years. The influenza vaccination rate was 6.80% (226/3 260) in 2017-2018 influenza epidemic season. After controlling for related factors, the awareness of the influenza vaccination schedule (OR=17.05, 95%CI: 5.86-49.59), vaccination frequency (OR=8.22, 95%CI: 2.98-22.61) and the free policy (OR=3.15, 95%CI: 1.49-6.67) had higher vaccination rate. Conclusion: The influenza vaccination rate of HCWs in tertiary hospitals of Xining city was low. Increasing the awareness of the vaccination schedule, frequency and free policy may promote the influenza vaccination rate of HCWs.

Pharmacokinetics of CYP2C9, CYP2C19, and CYP2D6 substrates in healthy Chinese and European subjects.

PURPOSE: The aim of this analysis is to compare the pharmacokinetics of drug substrates in healthy Chinese and European subjects of aligned CYP2C9, CYP2C19, or CYP2D6 enzyme activity, providing further insight into drivers of interethnic differences in pharmacokinetics. METHODS: Following identification of appropriate drug substrates, a comprehensive and structured literature search was conducted to identify single-dose pharmacokinetic data in healthy Chinese or European subjects with reported CYP2C9, CYP2C19, or CYP2D6 activity (genotype or phenotype). The ratio of drug AUC in the Chinese and European subjects classified with aligned enzyme activity was calculated (ethnicity ratio (ER)). RESULTS: For 22/25 drugs identified, the ERs calculated indicated no or only limited interethnic differences in exposure (

[Comparing the immunogenicity and safety of sequential inoculation of sIPV followed by bOPV (â +â ¢) in different dosage forms].

Objective: To compare the safety and immunogenicity of two different sequential schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV) followed by typeⅠ+Ⅲ bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC) form or liquid dosage form). Methods: This randomized, blinded, single center, parallel-group controlled trial was done from September 2015 to June 2016 in Liuzhou, Guangxi province. Healthy infants aged ≥2 months were eligible for enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules. According to the bOPV dosage form each sequential schedules, the subjects again were divided into drug candy(DC) form or liquid dosage form group, being 1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid). According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We recorded adverse events during the clinical trial (399 participants who receive at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples (excluding the quitters or subjects against trial plan), using cell culture trace against polio virus neutralization test Ⅰ, Ⅱ, Ⅲ neutralizing antibody (GMT), calculating the antibody positive rate.PolioⅠ,Ⅱand Ⅲ antibody titers were assessed by virus-neutralizing antibody assay and the seroconversion (4-fold increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total 350 samples) . Results: During the vaccination, the incidence of AEs in 1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid) group were 79%, 76%, 80% and 74% (χ(2)=1.23, P=0.747) , respectively. The severe AEs in groups were 6%, 5%, 6% and 4% (χ(2)=0.57, P=0.903) , respectively, and none was considered to be vaccination related. 28 days after 3(rd) vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and 99% (χ(2)=0.94, P=0.815) , respectively, for type Ⅰ poliovirus; and 47%, 57%, 80%, 79% (χ(2)=31.56, P<0.001) , respectively, for type Ⅱ; and were 100%, 99%, 100%, 99% (χ(2)=2.02, P=0.568) , respectively, for type Ⅲ. In each group, the GMT of antibody against poliovirus typeⅠ were 4 539.68, 6 243.43, 6 819.53 and 7 916.29 (F=25.87, P<0.001) , respectively; Type Ⅱ were 12.98, 10.54, 63.75 and 84.21 (F=8.68, P=0.034) , respectively; Type Ⅲ were 1 172.55, 1 416.03, 2 648.89 and 3 250.75 (F=14.50, P=0.002) , respectively. Conclusion: On the same sequential schedules, there was no significant difference between the dosage forms, all of them showed good safety and immunogenicity. In the same dosage forms with different sequential schedules, the seroconversion rate was higher in 2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing antibody GMT level against polio type Ⅱ and Ⅲ after vaccination.

[Clinical value of Short Form-36 and clinical measures in a prospective cohort study of ankylosing spondylitis patients].

OBJECTIVE: To evaluate the clinical value of Short Form-36 (SF-36) questionnaire and the most commonly used clinical measures in a prospective cohort study of ankylosing spondylitis (AS) patients. METHODS: A total of 517 AS patients were collected from the Department of Rheumatology, Chinese PLA General Hospital from August 2013 to September 2015. The Quality of Life (QoL) was assessed by SF-36 questionnaire and compared with the general population. The correlations between QoL and clinical measures of AS, including the Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI) et al, were analyzed. RESULTS: BASDAI and BASFI were significantly correlated with SF-36 scores (r>0.3, P<0.01). Logistic multiple regression analysis showed that BASDAI, BASFI, BASMI and education had close correlation with the baseline global QoL, physical and mental health. Among these clinical measures, BASDAI variation showed the most important influence on the change of global QoL, physical health and mental health (OR=0.235, 0.209, 0.125; P<0.01). CONCLUSIONS: SF-36 can objectively reflect the QoL of patients with AS. Clinical measures such as BASDAI and BASFI show great application value in this prospective cohort study of AS patients.

Low expression of microRNA-21 contributes to LPS-induced osteoblast cell apoptosis through up-regulation of OAS1.

Lipopolysaccharide (LPS) is a critical component of the outer membrane of Gram—negative bacteria. Many cellular signals that are activated by Gram—negative bacteria are initiated by LPS. LPS triggers not only inflammatory responses, but also activates pro—apoptotic signals in a series of human cell types. However, there is relatively minimal data on the microRNA—dependent mechanism(s) of LPS—induced functional activity in osteoblast cells. CCK—8 assay and flow cytometry were used to measure cell viability and apoptosis, respectively. RT—PCR and western blot were performed to determine the mRNA and protein expression in osteoblast cells. In this study, we found that LPS triggered apoptosis in osteoblastic hFOB1.19 cells and induced a low expression of the miRNA—21. Furthermore, through the gene microarray technique, OAS1 was screened and later confirmed to be the target gene which was up—regulated in response to the low expression of miRNA—21. Knockdown of OAS1 by specific siRNAs significantly rescued the LPS—induced hFOB1.19 cell apoptosis. Our data suggest that LPS induces low expression of miRNA—21which consequently causes the up—regulation of the downstream gene OAS1 and eventually triggers apoptosis in hFOB1.19 cells. Knockdown of OAS1 rescues LPS—induced cell death and thus may be a promising therapeutic strategy for orthopedic diseases.

Comparison of efficacy and toxicity profiles between paclitaxel/lobapoatin- and cisplatin/5-fluorouracil-based concurrent chemoradiotherapy of advanced inoperable oesophageal cancer.

BACKGROUND AND AIM: Current chemoradiotherapy doesn't usually effectively control oesophageal cancer progression. This study assessed the efficacy and toxicity profiles of paclitaxel/lobaplatin (TL)- and cisplatin/5-fluorouracil (PF)-based concurrent chemoradiotherapy (CCRT) in patients with advanced inoperable oesophageal cancer. METHODS: A total of such 68 patients was recruited and randomised to receive TL or PF-based CCRT. Radiotherapy was given at a total dose of 60-70 Gy over 6 weeks. In the TL group of patients, paclitaxel 60 mg/m(2) was administered intravenously on day 1, 8 and 15 and lobaplatin 30 mg/m(2) was administered on day 2 in two cycles at 3-week intervals. In the PF group, cisplatin 75 mg/m(2) was administered intravenously on day 1, and 5-fluorouracil 500 mg/m(2) and leucovorin 200 mg/m(2) were administered intravenously daily for 5 days in two cycles at 3-week intervals. Adverse events, treatment response and follow-up data were collected. RESULTS: The treatment response rates were 73.53% and 50.00% in the TL and PF groups respectively (P = 0.040). The median tumour progression-free survival (PFS) was 13.0 and 6.5 months in the TL and PF groups respectively (P = 0.034). Compared with PF group, the TL group demonstrated decreased grade 3/4 nausea and vomiting (5.88% vs 35.29%, P = 0.003), decreased granulocytopenia (11.76% vs 32.35%, P = 0.041) and platelet count reduction (32.5% vs 8.8%, P = 0.016). CONCLUSIONS: The TL treatment regimen demonstrated higher efficacy with less overall toxicity in patients with advanced inoperable oesophageal cancer compared with the PF regimen. Further study is warranted to validate our current observations.

Association between the LXRα polymorphism and stroke in a Chinese population.

We examined the relationship between the liver X receptor α gene (LXRα) polymorphism and the susceptibility to stroke. We utilized the single fluorescent-labeled probe technique to detect the genotype of rs12221497 in the LXRα gene in 400 stroke patients and 400 healthy control subjects. The difference in genotype distribution between the 2 groups was analyzed using the chi-square test. Serum lipids and glucose levels between the different genotypes were also compared. We found that the risk of stroke in carriers with the AA + GA genotype was 2.02-fold higher than that in GG genotype carriers (odds ratio = 2.02, 95% confidence interval = 1.18-2.87, P < 0.05), and that the risk of stroke in carriers with the A allele increased by 0.606-fold compared to that in G allele carriers (odds ratio = 1.606, 95% confidence interval = 1.158-2.228). Logistic regression analysis showed that after adjusting for other confounding factors, the A allele was an independent risk for stroke. However, there were no differences in serum lipids and glucose levels between each genotype. We conclude that the rs12221497 polymorphism in the LXRα gene was associated with the susceptibility to stroke in a Han Chinese population.