Bayesian two-stage design for phase II oncology trials with binary endpoint.

In phase II oncology trials, two-stage design allowing early stopping for futility and/or efficacy is frequently used. However, this design based on frequentist statistical approaches could not guarantee a high posterior probability of attending the pre-specified clinically interesting rate from a Bayesian perspective. Here, we proposed a new Bayesian design enabling early terminating for efficacy as well as futility. In addition to the clinically uninteresting and interesting response rate, a prior distribution of response rate, the minimum posterior threshold probabilities and the lengths of the highest posterior density intervals were specified in the design. Finally, we defined the feasible design with the highest total effective predictive probability. We studied the properties of the proposed design and applied it to an oncology trial as an example. The proposed design ensured that the observed response rate fell within prespecified levels of posterior probability. The proposed design provides an alternative design to single-arm two-stage trials.

Unicuspid Aortic Valve: A Rare Congenital Anomaly.

Unicuspid aortic valve (UAV) is a rare congenital aortic valve anomaly. It has 2 subtypes and often is associated with aortic valve dysfunction and corresponding clinical presentations. Echocardiography is the first choice of diagnostic method for UAV. Three-dimensional echocardiography has played an increasingly important role in diagnosis, intraprocedural guidance, and post-procedural assessment in recent years. There remain challenges in distinguishing UAV from bicuspid aortic valve or tricuspid aortic valve. Misdiagnosis is most resulted from raphes or leaflet calcifications. Multi-modality imaging has obvious advantages over single-modality imaging and is crucial for UAV diagnosis. Accurate identification of aortic valve morphology is important to choose the best treatment. Aortic balloon valvoplasty, surgical valvotomy, commissurotomy, Ross procedure, surgical valve repair, and surgical replacement are most common treatment modalities of UAV. In this review, we aim to discuss UAV including epidemiology, definition, classification, diagnostic importance and necessity, valvular function, clinical presentation, associated disorders, noninvasive diagnostic modalities, and therapeutic approaches.

Ethnic disparities in stillbirth risk in Yunnan, China: a prospective cohort study, 2010-2018.

BACKGROUND: Racial and ethnic disparities in stillbirth risk had been documented in most western countries, but it remains unknown in China. This study was to determine whether exist ethnic disparities in stillbirth risk in mainland China. METHODS: Pregnancy outcomes and ethnicity data were obtained from the National Free Preconception Health Examination Project (NEPHEP), a nationwide prospective population-based cohort study conducted in Yunnan China from 2010-2018. The Han majority and other four main minorities including Yi, Dai, Miao, Hani were investigated in the analysis. The stillbirth hazards were estimated by life-table analysis. The excess stillbirth risk (ESR) was computed for Chinese minorities using multivariable logistic regression. RESULTS: Compared with other four minorities, women in Han majority were more likely to more educated, less multiparous, and less occupied in agriculture. The pattern of stillbirth hazard of Dai women across different gestation intervals were found to be different from other ethnic groups, especially in 20-23 weeks with 3.2 times higher than Han women. The ESR of the Dai, Hani, Miao, and Yi were 45.05, 18.70, -4.17 and 12.28%, respectively. Adjusted for maternal age, education, birth order and other general risk factors, the ethnic disparity still persisted between Dai women and Han women. Adjusted for preterm birth further (gestation age <37 weeks) can reduce 16.91% ESR of Dai women and made the disparity insignificant. Maternal diseases and congenital anomalies explained little for ethnic disparities. CONCLUSIONS: We identified the ethnic disparity in stillbirth risk between Dai women and Han women. General risk factors including sociodemographic factors and maternal diseases explained little. Considerable ethnic disparities can be attributed to preterm birth.

Thromboembolic risks associated with paroxysmal and persistent atrial fibrillation in Asian patients: a report from the Chinese atrial fibrillation registry.

BACKGROUND: Several studies have reported on atrial fibrillation (AF) outcomes, including thromboembolism in patients with paroxysmal and non-paroxysmal AF; however the findings still remain controversial on whether risks differ between these clinical subtypes and limited data are available in Asian cohorts. METHODS: We compared the risk of thromboembolism between paroxysmal and persistent AF patients, in a large contemporary Chinese cohort study. A total of 8529 non-valvular atrial fibrillation (NVAF) patients from the Chinese Atrial Fibrillation Registry (CAFR) study were enrolled. The study subjects were divided into two groups: paroxysmal AF (PaAF, defined as AF lasting within 7 days, n = 4642) and persistent AF (PeAF, lasting over 7 days, n = 3887) groups. RESULTS: In non-anticoagulated patients, PeAF group demonstrated a higher risk of stroke, all-cause death, cardiac/ non-cardiac death and composition of stroke/ transient ischemic attack (TIA)/peripheral thromboembolism (PT)/all-cause death, compared to the PaAF group. No significant difference was found in anticoagulated subjects. On multivariate analysis in non-anticoagulated patients, age ≥ 75 years (P = 0.046) and prior stroke/TIA/PT (P = 0.018) but not AF type (P = 0.63) were significantly associated with the risk of stroke/TIA/PT events. CONCLUSIONS: Stroke, all-cause death and cardiac/non-cardiac death in Chinese NVAF population was increased in non-anticoagulated PeAF patients compared with PaAF group, but same between anticoagulated PeAF and PaAF patients. After adjustment, AF type was not an independent predictor of thromboembolism in NVAF patients. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OCH-13003729. Registered 22 October 2013.

Ablation Versus Medical Therapy for Atrial Fibrillation in the Elderly: A Propensity Score-Matched Comparison.

BACKGROUND Whether ablation therapy reduces the risk of death and embolic events in elderly patients with atrial fibrillation (AF) remains unclear. MATERIAL AND METHODS AF patients ≥65 years old receiving either catheter ablation or non-ablation therapy at 2 tertiary and 2 non-tertiary hospitals in Beijing from November 2009 to December 2012 were enrolled. Patients were followed up every 6 months for information on treatment and clinical event occurrence. A propensity score matching algorithm produced comparable 2 groups of patients treated with ablation or non-ablation. Rates of a composite of all-cause death, non-fatal stroke, and peripheral embolism were the primary outcomes. Each composite component and major bleeding were the secondary outcomes. RESULTS There were 596 ablated patients and 1144 patients with non-ablation therapy enrolled. Propensity score algorithm matched 347 comparable pairs of patients. Patient characteristics variables were well balanced. During 523.5 and 497.5 patient-years follow-up, respectively, ablation therapy was associated with a significant lower risk of experiencing the primary composite outcome (hazard ratio [HR]=0.40; 95% confidence interval [CI]: 0.19-0.85), all-cause death (HR=0.13 95% CI: 0.04-0.43), and major bleeding (HR=0.23; 95% CI: 0.12-0.67), without apparent heterogeneity by age, sex, and AF type, and for risk score subgroups. CONCLUSIONS In this propensity-matched elderly sample, ablation therapy was associated with lower risk of composite outcome consisting of all-cause death, non-fatal stroke, and peripheral embolism, and therefore might be an alternative to conservative therapy.

Rare Simultaneous Left and Right-Sided Native Valve Infective Endocarditis Caused by Rare Bacterium.

Simultaneous left and right-sided native valve infective endocarditis (IE) is rare. Staphylococcus aureus was the predominant organism for bilateral IE. Shunt diseases are common risk factors of both-sided IE. Streptococcus anginosus (S. anginosus) is usually associated with pyogenic infections, but rarely a cause of IE. Here we present an extremely rare case of simultaneous left and right-sided native valve IE affecting the mitral and tricuspid valves caused by S. anginosus in an adult patient that has not been reported in the literature previously, particularly without the most frequent predisposing factors of IE. A 66-year-old man was admitted due to generalized fatigue, chills, malaise, and intermittent fevers for 1 year. A grade III-IV/VI systolic murmur at the mitral area and a III/VI systolic murmur at the tricuspid area were noted on physical examination. Laboratory evaluation revealed an elevated erythrocyte sedimentation rate and C-reactive protein level, and high fasting blood glucose. Blood culture was positive for S. anginosus. Echocardiography revealed vegetations in both sides of the heart: a large mitral valve vegetation with severe mitral regurgitation, as well as another vegetation on the tricuspid valve with moderate regurgitation. The case highlights a rare pathogen of both-sided IE, a rare presentation of S. anginosus infection, and several points worthy of note in echocardiography of IE.

Current Status and Time Trends of Oral Anticoagulation Use Among Chinese Patients With Nonvalvular Atrial Fibrillation: The Chinese Atrial Fibrillation Registry Study.

BACKGROUND AND PURPOSE: Reported rates of oral anticoagulation (OAC) use have been low among Chinese patients with atrial fibrillation (AF). With improved awareness, changing guidelines, this situation may be changing over time. We aimed to explore the current status and time trends of OAC use in Beijing. METHODS: We used the data set from the Chinese Atrial Fibrillation Registry (CAFR), a prospective, multicenter, hospital-based registry study involving 20 tertiary and 12 nontertiary hospitals in Beijing. A total of 11 496 patients with AF were enrolled from 2011 to 2014. RESULTS: Seven thousand nine hundred seventy-seven eligible patients were included in this ancillary study. The proportions of OAC use were 36.5% (2268/6210), 28.5% (333/1168), and 21.4% (128/599) for patients with CHA2DS2-VASc scores ≥2, 1, and 0, respectively. Persistent AF, history of stroke/transient ischemic attack/peripheral embolism, diabetes mellitus, higher body mass index, and tertiary hospital management were factors positively associated with OAC use, whereas older age, previous bleeding, hypercholesterolemia, and established coronary artery disease were factors negatively associated with OAC use. Among patients with CHADS2 scores ≥2 and CHA2DS2-VASc scores ≥2, the proportion of OAC use increased from 31.3% to 64.5% and 30.2% to 57.7%, respectively, from 2011 to 2014. Variation in OAC use was substantial among different hospitals. CONCLUSIONS: An improvement of OAC use among Chinese patients with AF in Beijing is observed in recent years although only 36.5% of patients with CHA2DS2-VASc score ≥2 received OAC. However, variations between different hospitals were large, suggesting that better education and awareness are needed to improve efforts for stroke prevention among AF patients. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

Rationale and design of the Chinese Atrial Fibrillation Registry Study.

BACKGROUND: Robust data on the contemporary management of atrial fibrillation (AF) patients in China are limited. Importantly current practice in AF management has changing dramatically in recent years. Data from a large registry study will enable us to evaluate the uptake and outcomes with different therapies in a large Chinese AF population. METHODS/DESIGN: The Chinese Atrial Fibrillation Registry study (CAFR) aims to enroll 20,000 consecutive atrial fibrillation (AF) patients from 32 tertiary and non-tertiary hospitals in Beijing, China, and follow up these patients every 6 months until 2020. Key data collected includes basic sociodemographic information, symptoms and signs, medical history, results of physical examination and laboratory test, details of treatments and personal insurance status. For patients who consent, 5 ml of blood sample will be stored at -80 °C for future analyses of biomarkers. At each 6 month follow up visit, data relating to clinical outcomes will be collected. Data from a randomly selected 10 % of patients will be internally validated with their raw source data. Ischemic stroke events will be adjudicated by an independent endpoint committee. DISCUSSION: CAFR will be one of the largest registries of Asian AF patients (and the largest in Chinese AF patients), as well as providing the longest follow up. This study would provide a valuable opportunity for 'real world' clinical epidemiology with insights into the uptake (and outcomes) of contemporary AF management. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OCH-13003729 . Registered 22 October 2013.

GradMDM: Adversarial Attack on Dynamic Networks.

Dynamic neural networks can greatly reduce computation redundancy without compromising accuracy by adapting their structures based on the input. In this paper, we explore the robustness of dynamic neural networks against energy-oriented attacks targeted at reducing their efficiency. Specifically, we attack dynamic models with our novel algorithm GradMDM. GradMDM is a technique that adjusts the direction and the magnitude of the gradients to effectively find a small perturbation for each input, that will activate more computational units of dynamic models during inference. We evaluate GradMDM on multiple datasets and dynamic models, where it outperforms previous energy-oriented attack techniques, significantly increasing computation complexity while reducing the perceptibility of the perturbations https://github.com/lingengfoo/GradMDM.

Privacy-preserving household load forecasting based on non-intrusive load monitoring: A federated deep learning approach.

Load forecasting is very essential in the analysis and grid planning of power systems. For this reason, we first propose a household load forecasting method based on federated deep learning and non-intrusive load monitoring (NILM). As far as we know, this is the first research on federated learning (FL) in household load forecasting based on NILM. In this method, the integrated power is decomposed into individual device power by non-intrusive load monitoring, and the power of individual appliances is predicted separately using a federated deep learning model. Finally, the predicted power values of individual appliances are aggregated to form the total power prediction. Specifically, by separately predicting the electrical equipment to obtain the predicted power, it avoids the error caused by the strong time dependence in the power signal of a single device. In the federated deep learning prediction model, the household owners with the power data share the parameters of the local model instead of the local power data, guaranteeing the privacy of the household user data. The case results demonstrate that the proposed approach provides a better prediction effect than the traditional methodology that directly predicts the aggregated signal as a whole. In addition, experiments in various federated learning environments are designed and implemented to validate the validity of this methodology.

Internal versus external fixation for unstable distal radius fractures: an up-to-date meta-analysis.

PURPOSE: Our aim was to compare the effect of internal vs external fixation for unstable distal radius fractures regarding postoperative complications, clinical results and radiological outcomes. METHODS: We selected PubMed; Cochrane Library; EMBASE; BIOSIS; Ovid and the relevant English orthopaedic journals and pooled data from ten eligible randomised controlled trials containing 738 patients to conduct a subgroup analysis according to different periods of follow-up. Our aim was to summarise the best available evidence. RESULTS: Results showed that compared with external fixation, internal fixation led to significantly fewer total surgical complications [95% confidence interval (CI) 0.39-0.81, P = 0.002] and reduced the incidence of pin-track infections (95% CI 0.08-0.46, P = 0.0002) after a one year follow-up. For clinical results, grip strength (95% CI 1.59-8.25, P = 0.004), supination (95% CI 13.99-48.83, P = 0.0004) and pronation (95% CI 5.61-26.09, P = 0.002) were superior in the internal fixation group six weeks postoperatively, and the same results were obtained three months postoperatively for grip strength (95% CI 3.21-13.47, P = 0.001) and supination (95% CI 3.61-16.01, P = 0.002). Meanwhile, the Disabilities of the Arm, Shoulder and Hand (DASH) score was superior in the internal fixation group at three months (95% CI -20.62 to -2.07, P = 0.02) and after one year (95% CI -14.37 to -2.32, P = 0.007) follow-up. CONCLUSIONS: We suggest that the final results are significant and there is some evidence supporting the use of open reduction and internal fixation.

Design and Analysis of a Biosimilar Bridging Study with a Prediction Interval-Based Consistency Test.

The development of biosimilars has substantially increased in recent years. A biosimilar is a biological product which is highly similar to a licensed biological product (reference product), with no clinically meaningful differences between the proposed biosimilar and the reference product. A bridging study is a viable strategy to bring an approved biosimilar product from the original region(s) to new regions or countries. While the bridging concept and the principles of conducting bridging studies for innovative products outlined in ICH E5 guidance are informative for biosimilar development, existing statistical strategies for designing and analyzing a bridging study may not be directly applicable when the biosimilar global study compares the biosimilar product to a reference product as control. In this paper, we present a novel and practical statistical methodology for designing and analyzing a biosimilar bridging study based on a prediction interval-based consistency test for assessing consistency between the bridging study and the biosimilar global study. We prove analytically that the method has the desired statistical properties (i.e., high power when the two studies are perfectly consistent or nearly consistent in efficacy and type I error control when the two studies are clearly inconsistent in efficacy). We present a numerical example to illustrate that the implementation of the method is straightforward in practice. We also discuss the application of the method to various endpoints and metrics.

Specificity and application of SOX2 antibody.

Sox2 is known to play an important role in maintaining the totipotency and self-renewal of embryonic stem cells. The purpose of this study was to prepare an anti-chicken Sox2 polyclonal antibody using prokaryotic expression techniques, to evaluate its specificity and to use it to investigate the expression and distribution of Sox2 in the chicken brain and lungs. The chicken Sox2 gene was amplified and subcloned to a pET-30a vector to construct a prokaryotic expression vector, pET-Sox2. A His-Sox2 fusion protein was expressed, purified, and used to prepare an antichicken Sox2 polyclonal antibody. Western blotting revealed that the antichicken Sox2 antibody could specifically bind not only to the purified His-Sox2 fusion protein but also to the endogenous Sox2 protein in the testes of chicken, showing a distinct dose-dependent relationship between antigen and Sox2 antibody. Indirect immunofluorescent staining of Sox2-overexpressing cells showed strong nuclear and diffuse cytoplasmic immunoreactivity for Sox2 in the antichicken Sox2 antibody-staining cells. A CRISPR/Cas9 effector system-mediated Sox2 knockdown assay indicated that Sox2 expression in HEK 293T cells was downregulated in the presence of doxycycline but upregulated in the absence of doxycycline. In addition, cryosectioning and immunohistochemical staining illustrated that most spermatogonia in the seminiferous tubules, and a small number of Sertoli and Leydig cells, were positive for Sox2. The antichicken Sox2 antibody was also successfully used to investigate the expression and distribution of Sox2 in the chicken cerebellar cortex, optic tectum, cerebral cortex, and lungs. The results of this study confirmed the specificity of the antichicken Sox2 polyclonal antibody, which will be available for the study of biological functions of the chicken Sox2 gene and the self-renewal mechanisms of chicken pluripotent stem cells.

Strategic Shift of Statistical Review on Data Quality Assessment for New Drug Applications in China.

Data quality is critical for clinical trials to obtain robust conclusions about drug safety and efficacy evaluation. Effective data quality evaluation has been one of the major obstacles to new drug approvals in China, which hinders innovation in drug discovery and development ultimately. To improve the data quality submitted for regulatory drug approval, the China Food and Drug Administration (CFDA) has issued serial official announcements and industry guidelines regarding improvement of the clinical trial data integrity and quality since 2015. These announcements and follow-up measures are shaping up the entire pharmaceutical industry in China. While data quality is being strongly emphasized more than ever at the trial conduction phase, it is still an open question about how to assess data quality effectively at the review stage. Thus, this article describes the authors' standpoints to assess the quality and integrity of submitted clinical data via statistical review methods including advanced risk-based approaches, which may bring significant impact to new drug applications and motivate sustainable development of innovative medicines in China.

China National Medical Products Administration approval summary: anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy.

BACKGROUND: On May 8, 2018, the China National Medical Products Administration (NMPA) approved anlotinib, an orally administered anti-angiogenesis inhibitor, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have progressed after treatment with two or more lines of prior systemic chemotherapy. China NMPA reviewed and inspected a regional double-blinded, placebo-controlled, Phase III trial comparing the overall survival (OS) of NSCLC patients between the anlotinib and placebo arms. A total of 437 patients were randomized (2:1) to receive either anlotinib (n = 294) or placebo (n = 143) once daily on a 2-week on and 1-week off schedule. Patients with epidermal growth factor receptor (EGFR) or activating anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on NMPA-approved therapy. Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China. The approval was based on a statistically and clinically significant improvement in median OS with anlotinib (9.46 months) compared with placebo [6.37 months; hazard ratio (HR]) = 0.70, 95% confidence interval (CI) = 0.55-0.89; two-sided log-rank P = 0.002]. The confirmed objective response rate (ORR) was 9.2% in the anlotinib arm and 0.7% in the placebo arm. The median duration of response (DoR) was 4.83 months, with a 95% CI of 3.31-6.97 months. The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors. Common adverse drug reactions (ADRs) in anlotinib-treated patients included hypertension (67.4%), hand-foot syndrome (43.9%), hemoptysis (14.0%), thyroid stimulating hormone (TSH) elevation (46.6%), and corrected QT interval (QTc) prolongation (26.2%). SHORT CONCLUSION: Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.

Survival after neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for resectable esophageal carcinoma: A meta-analysis.

BACKGROUND: The efficacy of surgery alone for patients with locally advanced esophageal cancer (EC) is still unsatisfactory. Presently, induction therapy followed by surgery is the standard treatment. Preoperative chemotherapy (CT) and chemoradiation (CRT) are proven effective induction therapies; however, few sample studies have addressed these treatments, thus, their superiority remains uncertain. We performed a systemic review and meta analysis to test the hypothesis that induction CRT prior to surgery could improve survival compared with induction CT alone. METHODS: A comprehensive search of PubMed and the Ovid database for relevant studies comparing EC patients undergoing resection after treatment with induction CT alone or induction CRT was conducted. Hazard ratios (HR) and 95% confidence intervals (95% CI) were extracted from these studies to provide pooled estimates of the effect of induction therapy on overall survival. RESULTS: Five studies met the criteria for analysis. Statistical analysis demonstrated a survival benefit of induction CRT compared with induction CT alone (HR0.73, 95% CI 0.61-0.89; P = 0.002). Further analysis showed that induction CRT perioperative mortality and complication rates were higher than for induction CT alone (HR 2.96, 95% CI 1.38-6.37; HR1.6, 95% CI 1.30-1.98; P = 0.01, respectively). CONCLUSIONS: Published evidence comparing the different efficacies of induction CT and induction CRT is sparse, with few samples of adenocarcinoma. This analysis supports the view that, compared with induction CT, induction CRT could achieve a long-term survival benefit in EC patients.

Uptake of evidence-based statin therapy among atrial fibrillation patients in China: A report from the CAFR (Chinese Atrial Fibrillation Registry) Study.

BACKGROUND: Atrial fibrillation (AF) is associated with increased incidence of cardiovascular disease, and hence, statin therapy is indicated in majority of AF patients. METHODS AND RESULTS: We analyzed data from the Chinese Atrial Fibrillation Registry (CAFR) involving 11,496 AF patients from 2011 to 2014. Practice patterns of statin therapy and factors associated with statin underuse were analyzed. Based on the 2013 ACC/AHA cholesterol management guidelines, statins should be recommended for 67.4% (7720/11,461) of AF participants in CAFR, but only 43.4% (3352/7720) with appropriate indications were taking statins. Statin underuse in AF patients was independently associated with male sex, tertiary hospital treatment, outpatient attendance, and absence of 'high risk' cardiovascular risk factors (overweight, diabetes, coronary heart disease, stroke/transient ischemic attack/peripheral embolism and hypertension). CONCLUSIONS: A high proportion of Chinese AF patients had indications for statin therapy. Evidence-based statin prescribing was suboptimal in this population. Greater efforts should be made to improve a holistic approach to cardiovascular risk management in the Chinese AF population.

The Effects of a Community-Based Sodium Reduction Program in Rural China - A Cluster-Randomized Trial.

BACKGROUND: Average sodium intake and stroke mortality in northern China are both among the highest in the world. An effective, low-cost strategy to reduce sodium intake in this population is urgently needed. OBJECTIVE: We sought to determine the effects of a community-based sodium reduction program on salt consumption in rural northern China. DESIGN: This study was a cluster-randomized trial done over 18 months in 120 townships (one village from each township) from five provinces. Sixty control villages were compared to 60 intervention villages that were given access to a reduced-sodium, added-potassium salt substitute in conjunction with a community-based health education program focusing on sodium reduction. The primary outcome was the difference in 24-hour urinary sodium excretion between randomized groups. RESULTS: Among 1,903 people with valid 24-hour urine collections, mean urinary sodium excretion in intervention compared with control villages was reduced by 5.5% (-14mmol/day, 95% confidence interval -26 to -1; p = 0.03), potassium excretion was increased by 16% (+7mmol/day, +4 to +10; p<0.001), and sodium to potassium ratio declined by 15% (-0.9, -1.2 to -0.5; p<0.001). Mean blood pressure differences were -1.1 mm Hg systolic (-3.3 to +1.1; p = 0.33) and -0.7 mm Hg diastolic (-2.2 to +0.8, p = 0.35) and the difference in the proportion with hypertension was -1.3% (-5.1 to 2.5, p = 0.56). CONCLUSION: There were clear differences in population sodium and potassium intake between villages that were most likely a consequence of increased use of salt substitute. The absence of effects on blood pressure reflects the moderate changes in sodium and potassium intake achieved. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01259700.

Severalconsiderationsontherelatedissuesofclinicaltrialdesignofchimericantigen receptorT lymphocytes in the treatment of lymphohematopoietic malignancies / 中国肿瘤生物治疗杂志

@# Chimeric antigen receptor (CAR) T lymphocyte has shown attractive prospects in the treatment of lymphohematopoietic malignancies including B-cell lymphoblastic leukemia, B-cell lymphoma and multiple myeloma. Many applicants have submitted investigational new drug (IND) applications to Center for Drug Evaluation of National Medical Products Ggency, however, many of the INDs have problems in patient selection, prognostic indicators and risk management, etc, which might hinder the evaluation of the safety and efficacy of CAR-T cells. Thus, we made some suggestions on the above-mentioned problems through summarizing clinical experience and communicating with domestic clinical experts, which the sponsors and researchers can refer to when conducting CAR-T cell clinical trials for registration.

Adoptive immunotherapy of cytokine-induced killer cell therapy in the treatment of non-small cell lung cancer.

AIM: The aim of this study was to systemically evaluate the therapeutic efficacy of cytokine-induced killer (CIK) cells for the treatment of non-small cell lung cancer. MATERIALS AND METHODS: A computerized search of randomized controlled trials for CIK cell-based therapy was performed. The overall survival, clinical response rate, immunological assessment and side effects were evaluated. RESULTS: Overall, 17 randomized controlled trials of non-small cell lung cancer (NSCLC) with a total of 1172 patients were included in the present analysis. Our study showed that the CIK cell therapy significantly improved the objective response rate and overall survival compared to the non-CIK cell-treated group. After CIK combined therapy, we observed substantially increased percentages of CD3+, CD4+, CD4+CD8+, CD3+CD56+ and NK cells, whereas significant decreases were noted in the percentage of CD8+ and regulatory T cell (Treg) subgroups. A significant increase in Ag-NORs was observed in the CIK-treated patient group (p = 0.00001), whereas carcinoembryonic antigen (CEA) was more likely to be reduced to a normal level after CIK treatment (p = 0.0008). Of the possible major side effects, only the incidence of fever in the CIK group was significantly higher compared to the group that received chemotherapy alone. CONCLUSION: The CIK cell combined therapy demonstrated significant superiority in the overall survival, clinical response rate, and T lymphocytes responses and did not present any evidence of major adverse events in patients with NSCLC.