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Objective: To investigate the main components and potential mechanism of Shuxuening Injection (SXNI) in the treatment of myocardial ischemia-reperfusion injury (MIRI) through network pharmacology and in vivo research. Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose (3.68 mg/kg), medium-dose (7.35 mg/kg), and high-dose (14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group (14.7 mg/kg), SXNI+LY294002 group, and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride (TTC) double staining, hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathway was closely related to SXNI treatment of MIRI. In vivo experiments showed that SXNI reduced the myocardial infarction area in the model group, improved rat heart pathological damage, and reduced the cardiomyocyte apoptosis rate (all P<0.01). After SXNI treatment, the p-PI3K/PI3K and p-AKT/AKT ratios as well as B-cell lymphoma-2 (Bcl-2) protein expression in cardiomyocytes were increased, while the Bax and cleaved caspase 3 protein expression levels were decreased (all P<0.05). LY294002 partially reversed the protective effect of SXNI on MIRI. Conclusion: SXNI protects against MIRI by activating the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Analyzing eye movements of workers in safe and unsafe behaviors can reduce accidents. With a video-based method, the angular velocity of gaze direction (AVGD) represents micro-movements in gaze and angular velocity in saccade is used to analyze eye movements. A similar behavior simulation experiment is designed to collect operation videos, and an eye movement information extraction and processing framework is constructed to quantify and analyze eye movements. The results show that: the root mean square and movement frequency of AVGD can be used to recognize unsafe behavior; in operations with attention target fixation, compared with safe behavior, workers in unsafe behavior have higher angular velocity, movement frequency and turn frequency of eye movements; and in operations with attention target change, eye movement rules of workers in safe and unsafe behaviors depend on operation types. The results can provide features for unsafe behavior recognition and theoretical bases for safety training. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to investigate the diagnostic accuracy of store-and-forward tele-ophthalmology consultations for non-diabetic patients, aged 40 and above, presenting with vision impairment of 3 months or more, in terms of cataracts, glaucoma, and age-related macular degeneration. Methods: This is a prospective comparative study. Enrolled subjects were independently assessed by both tele-ophthalmology and face-to-face assessment. Agreement level between the two modalities for diagnosis and severity were compared using kappa statistic. Diagnostic accuracy of tele-ophthalmology was determined using the face-to-face consultation serving as the gold standard. Costs were compared by calculating the downstream costs generated by each modality in terms of investigations and treatment. Results: A total of 860 eyes of 430 patients were assessed during the study period. Tele-ophthalmology consultations had significantly high agreement with face-to-face consultations in the diagnosis and grading of all three ocular conditions; cataracts, glaucoma, and AMD. Diagnosis and grading of cataracts and AMD reached κ values of > 0.8, while diagnosis and grading of glaucoma reached κ values between 0.61 and 0.8. In terms of diagnostic accuracy, tele-ophthalmology consultations were highly sensitive and specific for AMD with greater than 99% sensitivity and specificity achieved by tele-ophthalmology. There was high specificity when diagnosing cataracts, but lower sensitivity at 87.8%. Conversely, there was high sensitivity for diagnosing glaucoma, but lower specificity at 76.5%. Downstream costs were similar between groups. Conclusions: Store-and-forward tele-ophthalmology consultations are accurate and comparable to face-to-face consultations for diagnosis and grading of cataracts, glaucoma, and AMD. [ABSTRACT FROM AUTHOR]

Background: Predictors besides symptoms of obstruction indicating small bowel stenosis are little known.Aims: To detect predictors of small bowel stenosis in balloon-assisted enteroscopy.Methods: Over a 6-year period, 461 patients had enteroscopy for suspected small intestinal disease. Details of clinical manifestations, medical history, demographic characteristics, findings of examinations, information on enteroscopy, and treatment were retrospectively collected based on medical records. Small bowel stenosis was defined as stricture that over-tube cannot go through in enteroscopy. Univariate and multivariate analyses were performed to identify predictors for small bowel stenosis.Results: A total of 314 patients had definite diagnosis after enteroscopy, imaging modalities, and/or even surgical exploration. They were included in this study for analyses. Mean age for them was 48.2 years old (range 15-81 years). Small bowel stenosis was present in 59 patients (18.8%). Analyses showed that CT/MRI indicating stenosis was significantly associated with severe stenosis (p = 0.014) but insignificant related to general stenosis (p = 0.097). Predictive factors that accompanied stenosis were age ≥ 60 years (OR = 2.1, 95% CI 1.1-4.0), underweight (BMI ≤ 18.5) (OR = 3.4, 95% CI 1.4-8.4), symptoms of obstruction (OR = 3.6, 95% CI 1.8-7.4), and overt small bowel bleeding (OR = 0.5, 95% CI 0.2-0.9).Conclusions: Small bowel stenosis more tended to occur to patients with symptoms of obstruction, no overt small bowel bleeding, age ≥ 60 years, or underweight. [ABSTRACT FROM AUTHOR]

Objective: Our study aimed to compare the predictive value of waist-to-height ratio (WHtR) for hyperuricemia with body mass index (BMI) and waist circumference (WC). Methods: This is a cross-sectional study of 9,206 South China residents (male/female: 4,433/4,773) aged 18–89 years recruited during years 2009–2010 and 2014–2015. Anthropometric measurements, serum uric acid, blood pressure, and plasma glucose, lipid, lipoprotein, and transferase levels were measured. Receiver operating characteristic (ROC) curve and logistic regression analyses were applied to evaluate the predictive values of anthropometric indices for hyperuricemia. Results: The prevalence of hyperuricemia increased significantly with higher quartiles of WHtR in both genders. The best cutoff points of WHtR to predict hyperuricemia are 0.52 for men and 0.49 for women and differed between different BMI and WC stratums. Although there was no significant difference between the area under the ROC curves, subjects in the top quartile of WHtR were at a highest risk of hyperuricemia (p for linear trend <0.001) and the adjusted ORs of WHtR (2.24–2.77 in men and 2.66–4.95 in women) were higher than those of BMI or WC in the multivariable regression model. Conclusions: WHtR was an independent and better predictor of hyperuricemia compared with BMI and WC. [ABSTRACT FROM AUTHOR]

Energy crises and environmental pollution have caused considerable concerns; duckweed is considered to be a promising new energy plant that may relieve such problems. Lemna aequinoctialis strain 6000, which has a fast growth rate and the ability to accumulate high levels of starch was grown in both Schenk & Hildebrandt medium (SH) and in sewage water (SW). The maximum growth rates reached 10.0 g DW m−2 day−1 and 4.3 g DW m−2 day−1, respectively, for the SH and SW cultures, while the starch content reached 39% (w/w) and 34% (w/w). The nitrogen and phosphorus removal rate reached 80% (SH) and 90% (SW) during cultivation, and heavy metal ions assimilation was observed. About 95% (w/w) of glucose was released from duckweed biomass hydrolysates, and then fermented by Angel yeast with ethanol yield of 0.19 g g−1 (SH) and 0.17 g g−1 (SW). The amylose/amylopectin ratios of the cultures changed as starch content increased, from 0.252 to 0.155 (SH) and from 0.252 to 0.174 (SW). Lemna aequinoctialis strain 6000 could be considered as valuable feedstock for bioethanol production and water resources purification. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s40123-022-00506-x. Correction to: Ophthalmol Ther https://doi.org/10.1007/s40123-022-00506-x During the typesetting stage an erroneous key summary point was added - "There are currently few cases in the literature reporting a relationship between COVID-19 vaccination and the occurrence of lichen planus.". [Extracted from the article]

Abstract: A simple multi-band QPSK signal transmission scheme, constructed by using an optical remote up-conversion technique and a Schottky diode RF detector, is theoretically analyzed and experimentally implemented in a 60-GHz millimeter wave (mm-wave) radio over fiber (RoF) system, for the first time. There is no need for complex system architecture or any expensive high-frequency clock source in our scheme. Simulation results show that our scheme is highly tolerant to fiber dispersion, compared with the conventional 60GHz multi-band RoF system. In the experimental demonstration, successful delivery of QPSK signals at two 60-GHz sub-bands is achieved over 50-km fiber and 4-m wireless distance. [Copyright &y& Elsevier]

Integrated transportation and land use studies are of major interest to planners because they consider the interaction between transportation development and land use change. Quantifying the impact of transport infrastructure on land use change is necessary for evaluating the role of transportation development in the process of land use and land cover change in the urban-rural fringe. Taking Qixia District of Nanjing City, Jiangsu Province, China as a typical urban-rural fringe area, this paper analyzes the patterns and characteristics of land use change along three major transportation arteries using land use data from 2000 and 2008. We examine the spatial differentiation and gradient of land use pattern around railway, expressway, and highway corridors to investigate whether land use change in the urban-rural fringe is related to distance from transportation arteries and to clarify the varying impacts of different forms of transport infrastructure on land use patterns. We find that construction land generally tends to be located close to major transportation arteries, and that railways have the most obvious influence on land use change in the urban-rural fringe, while the impact of expressways was not significant. We conclude that there exists a causal relationship between the presence of transportation arteries and land use change in the urban-rural fringe, but this relationship varies across different types of linear transport infrastructure. [ABSTRACT FROM AUTHOR]

Objectives: To compare the performance of double screening (measuring maternal serum levels of alpha-fetoprotein [AFP] and total beta-human chorionic gonadotrophin [hCG] as markers for Down syndrome) with that of triple screening (also measuring levels of unconjugated estriol [uE3]) in the second trimester of pregnancy, and to compare ethnic variance between Chinese and Caucasian populations.Methods: The study investigated 15096 normal singleton pregnancies and 24 pregnancies affected with Down syndrome. Frequency distributions of AFP, hCG, and uE3 levels were analyzed. Likelihood ratios (LRs) were calculated using the multiple of median value (MoM) of AFP, hCG, and uE3 as variables. After multiplying maternal age risk by the LR values for the markers used in double and triple screening, the specific risks obtained with double and triple screening were estimated. The detection rate (DR) and false-positive rate (FPR) were calculated at different cut-off points. The serum markers' levels were also compared with those of Caucasian women.Results: The median MoM value of hCG was higher in women with affected pregnancies (1.40) than those with unaffected pregnancies (1.00). However, the median MoMs of AFP and uE3 (0.79 and 0.68) were lower in affected than in unaffected pregnancies. At a FPR of 5%, the detection rates reached with double and triple screening were 50% and 66.7%, respectively. Ratios of the 3 serum markers' medians to those in a study with Caucasian women were 1.06 (range=1.04-1.09) for AFP, 1.14 (range=1.10-1.17) for hCG, and 1.28 (range=1.23-1.41) for uE3 for the relevant gestational weeks.Conclusion: Triple screening performed better than double screening in the second trimester. Ethnic variance should be taken into account in Down syndrome screening. [ABSTRACT FROM AUTHOR]

Different degrees of malnutrition is common in patients with liver cirrhosis, mainly manifested by protein - energy malnutrition. The nutritional status of patients is associated with their prognosis and survival rate. However, clinicians have not paid much attention to this fact, and malnutrition is often neglected in the patients with liver cirhosis. This paper reviews several nutritional assessment tools applied in recent years among patients with liver cirhosis and summarizes the characteristics of each tool, so as to provide a reference for nutritional as-sessment by clinicians. [ABSTRACT FROM AUTHOR]

Background: It is currently unknown whether intensive blood pressure (BP) lowering beyond that recommended would lead to more lowering of the risk of left ventricular hypertrophy (LVH) in patients with hypertension and whether reducing the risk of LVH explains the reported cardiovascular disease (CVD) benefits of intensive BP lowering in this population.Methods: This analysis included 8164 participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP <120 mm Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm Hg). Progression and regression of LVH as defined by Cornell voltage criteria derived from standard 12-lead ECGs recorded at baseline and biannually were compared between treatment arms during a median follow-up of 3.81 years. The effect of intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and CVD death) was compared before and after adjustment for LVH as a time-varying covariate.Results: Among SPRINT participants without baseline LVH (n=7559), intensive (versus standard) BP lowering was associated with a 46% lower risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68). Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those assigned to the intensive (versus standard) BP lowering were 66% more likely to regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31-2.11). Adjustment for LVH as a time-varying covariate did not substantially attenuate the effect of intensive BP therapy on CVD events (hazard ratio of intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64-0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment for LVH as a time-varying covariate, respectively).Conclusions: Among patients with hypertension but no diabetes mellitus, intensive BP lowering (target systolic BP <120 mm Hg) compared with standard BP lowering (target systolic BP <140 mm Hg) resulted in lower rates of developing new LVH in those without LVH and higher rates of regression of LVH in those with existing LVH. This favorable effect on LVH did not explain most of the reduction in CVD events associated with intensive BP lowering in the SPRINT trial.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062. [ABSTRACT FROM AUTHOR]

Electrocardiographic (ECG) Q- and ST-T–wave abnormalities predict coronary heart disease (CHD) and total mortality. No comparison has been made of the classification of these abnormalities by the 2 most widely used ECG coding systems for epidemiologic studies—the Minnesota Code (MC) and Novacode (NC). We evaluated 12-lead electrocardiograms from 64,597 participants (49 to 79 years old, 82% non-Hispanic white) in the Women''s Health Initiative clinical trial in 1993 to 1998, with a maximum of 11 years of follow-up. We used MC and NC criteria to identify Q-wave, ST-segment, and T-wave abnormalities for comparison. In total, 3,322 participants (5.1%) died during an average 8-year follow-up, and 1,314 had incident CHD in the baseline cardiovascular disease-free group. Independently, ECG myocardial infarction criteria by the MC or NC were generally equivalent and were strong predictors for CHD death and total mortality (hazard ratio 1.62, 95% confidence interval 1.05 to 2.51 for CHD death; hazard ratio 1.36, 95% confidence interval 1.09 to 1.71 for total mortality) in a multivariable analytic model. Electrocardiograms with major ST-T abnormalities by the MC or NC coding system were stronger in predicting CHD deaths and total mortality than was the presence of Q waves alone. In conclusion, the ECG classification systems for myocardial infarction/ischemia abnormalities from the MC and NC are valuable and useful in clinical trials and epidemiologic studies. ST-T abnormalities are stronger predictors for CHD events and total mortality than isolated Q-wave abnormalities. [Copyright &y& Elsevier]

Highlights: [•] Heavy ion irradiation mutagenesis was firstly applied in microalgae breeding. [•] The mutant HP-1 showed higher biomass production than the wild type Nannochloropsis. [•] Its lipid productivity was increased by 28% compared to the wild type. [•] The reason caused its higher biomass accumulation and lipid productivity was studied. [•] Further, its TAG content was higher and polar lipid was lower than the wild type. [Copyright &y& Elsevier]

Background: The tetravalent dengue vaccine (CYD-TDV) has been shown to provide protection against dengue disease over 5-year follow-up in participants with previous dengue infection, but increased the risk of dengue hospitalisation and severe dengue during long-term follow-up in those without previous dengue infection. WHO recommended pre-vaccination screening to identify those with previous dengue infection (ie, dengue seropositive) who would benefit from vaccination. We re-evaluated CYD-TDV efficacy in those identified as dengue seropositive using five commercially available immunoassays, and assessed immunoassay performance.Methods: We included participants in the immunogenicity subsets of the phase 3 CYD14 (NCT01373281) and CYD15 (NCT01374516) CYD-TDV efficacy trials, which enrolled children aged 2-16 years in 2011-12 in five countries in the Asia-Pacific region (CYD14) and five Latin American countries (CYD15). Participants assessed had received at least one injection of study drug (CYD-TDV or placebo) and had baseline samples available. We tested baseline samples by IgG-based immunoassays to classify baseline dengue serostatus, using two ELISAs (EUROIMMUN and Panbio) and three rapid diagnostic tests (RDTs; TELL ME FAST, SD BIOLINE, and OnSite). Vaccine efficacy in preventing symptomatic, hospitalised, and severe virologically confirmed dengue was determined for participants who tested positive by each immunoassay. The specificity and sensitivity of each immunoassay was determined as percentage negative and positive agreement compared with the reference algorithm, which used dengue plaque reduction neutralisation test with 50% and 90% cutoffs and non-structural protein 1 IgG ELISA results to assign baseline serostatus.Findings: Samples were available for 3967 participants, 2735 (69·0%) of whom were classified as seropositive by the reference algorithm. Vaccine efficacy against symptomatic virologically confirmed dengue in immunoassay-positive participants was high across all five immunoassays (EUROIMMUN ELISA 88·2% [95% CI 77·3 to 93·9], Panbio ELISA 87·6% [76·7 to 93·4], TELL ME FAST RDT 88·8% [67·0 to 96·2], SD BIOLINE RDT 82·8% [66·9 to 91·1], and OnSite RDT 89·7% [64·6 to 97·0]), as was vaccine efficacy against hospitalised virologically confirmed dengue (EUROIMMUN-ELISA 72·8% [38·9 to 87·9], Panbio ELISA 77·5% [52·8 to 89·3], TELL ME FAST RDT 92·4% [37·8 to 99·1], SD BIOLINE RDT 87·2% [54·5 to 96·4], and OnSite RDT 73·7% [-5·1 to 93·4]) and severe virologically confirmed dengue (EUROIMMUN ELISA 86·9% [-16·8 to 98·5], Panbio ELISA 91·3% [27·6 to 99·0], TELL ME FAST RDT 100·0% [not estimable to 100·0%], SD BIOLINE RDT 89·4% [9·6 to 98·8], and OnSite RDT 73·4% [-193·7 to 97·6]). The immunoassays exhibited high specificity (≥98·8% for all immunoassays apart from SD BIOLINE RDT) but variable sensitivities, with higher sensitivities observed for the ELISAs (EUROIMMUN 89·2% [87·9 to 90·3] and Panbio 92·5 [91·4 to 93·5]) than the RDTs (TELL ME FAST 52·5% [50·6 to 54·4], SD BIOLINE 71·1% [69·3 to 72·8], and OnSite 47·6% [45·7 to 49·5]).Interpretation: Our findings suggest that these immunoassays could be used for pre-vaccination screening for CYD-TDV as tools to assist risk stratification until more sensitive and convenient tests become available.Funding: Sanofi Pasteur. [ABSTRACT FROM AUTHOR]

Based on parametric studies, this paper studies the structural and aerodynamic properties of a typical wing-rotor system by considering additional coupling effects from the tip rotor. The governing equations are established by virtue of Yamanaka's theory and Hamilton's principle in an Euler–Bernoulli precision. In the derivation process, complex mode theory and the Rayleigh–Ritz approach are employed to obtain the analytical solution and the numerical solution, respectively, and a set of trial functions are generated for the sake of reliability. Two aeroelastic models are generated via steady and unsteady aerodynamic models to investigate the divergence and flutter performance, respectively, where the computational p-k method is adopted because of the gyros matrix. In case studies, the effectiveness of the numerical solution is validated through comparative analysis; thereafter, the aeroelastic solutions are further verified. The results demonstrate that the gyro effect and the thrust effect have significant influences on the fundamental structural and aeroelastic performances, and parametric designs have great potential to postpone aeroelastic instabilities. [ABSTRACT FROM AUTHOR]

Background: Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab.Methods: Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616.Findings: Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax.Interpretation: A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies.Funding: AbbVie Inc and Genentech Inc. [ABSTRACT FROM AUTHOR]

Background: New treatments have improved outcomes for patients with relapsed chronic lymphocytic leukemia (CLL), but complete remissions remain uncommon. Venetoclax has a distinct mechanism of action; it targets BCL2, a protein central to the survival of CLL cells.Methods: We conducted a phase 1 dose-escalation study of daily oral venetoclax in patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) to assess safety, pharmacokinetic profile, and efficacy. In the dose-escalation phase, 56 patients received active treatment in one of eight dose groups that ranged from 150 to 1200 mg per day. In an expansion cohort, 60 additional patients were treated with a weekly stepwise ramp-up in doses as high as 400 mg per day.Results: The majority of the study patients had received multiple previous treatments, and 89% had poor prognostic clinical or genetic features. Venetoclax was active at all dose levels. Clinical tumor lysis syndrome occurred in 3 of 56 patients in the dose-escalation cohort, with one death. After adjustments to the dose-escalation schedule, clinical tumor lysis syndrome did not occur in any of the 60 patients in the expansion cohort. Other toxic effects included mild diarrhea (in 52% of the patients), upper respiratory tract infection (in 48%), nausea (in 47%), and grade 3 or 4 neutropenia (in 41%). A maximum tolerated dose was not identified. Among the 116 patients who received venetoclax, 92 (79%) had a response. Response rates ranged from 71 to 79% among patients in subgroups with an adverse prognosis, including those with resistance to fludarabine, those with chromosome 17p deletions (deletion 17p CLL), and those with unmutated IGHV. Complete remissions occurred in 20% of the patients, including 5% who had no minimal residual disease on flow cytometry. The 15-month progression-free survival estimate for the 400-mg dose groups was 69%.Conclusions: Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL, including those with poor prognostic features. (Funded by AbbVie and Genentech; ClinicalTrials.gov number, NCT01328626.). [ABSTRACT FROM AUTHOR]

The association of electrocardiographic (ECG) abnormalities with cardiovascular disease and risk factors has been extensively studied in whites and African-Americans. Comparable data have not been reported in Hispanics/Latinos. The Hispanic Community Health Study/ Study of Latinos (HCHS/SOL) is a multicenter, community-based, prospective cohort study of men and women of diverse backgrounds aged 18 to 74 years who self-identified as Hispanic/Latinos. Participants (n = 16,415) enrolled from March 2008 to June 2011. We describe the prevalence of minor and major ECG abnormalities and examined their cross-sectional associations with cardiovascular disease and risk factors. The Minnesota code criteria were used to define minor and major ECG abnormalities. Previous cardiovascular disease and risk factors were based on data obtained at baseline examination. Significant differences in prevalent ECG findings were found between men and women. Major ECG abnormalities were present in 9.2% (95% confidence interval 8.3 to 10.1) of men and 6.6% (95% confidence interval 5.8 to 7.3) of women (p <0.0001). The odds of having major ECG abnormalities significantly increased with age, presence of ≥3 cardiovascular risk factors, and prevalent cardiovascular disease, in both men and women. Significant differences in major ECG abnormalities were found among the varying groups; Puerto Ricans and Dominicans had more major abnormalities compared with Mexican men and women. In conclusion, in a large cohort of Hispanic/Latino men and women, prevalence of major abnormalities was low, yet strong associations of major ECG abnormalities with cardiovascular disease and risk factors were observed in both men and women. [ABSTRACT FROM AUTHOR]

Xuanbai Chengqi decoction (XBCQ), a traditional Chinese medicine formulation, was reported to have a protective role in a variety of pulmonary infection diseases. However, its mechanism remains uncertain. In the current study, we investigated the potential mechanism of XBCQ, its therapeutic effects on organ injuries induced by sepsis and gut microbiota modulation. 80 Male Sprague Dawley rats were performed cecal ligation and puncture (CLP) for sepsis model and 60 of them were treated with different doses of XBCQ (3.78, 7.56, 15.12 g/Kg, 20 rats per group) twice per day. After the most valid dose was determined, another 40 rats were divided randomly into four groups: sham group, sham + XBCQ group, sepsis group, sepsis + XBCQ group. The sepsis + XBCQ group was treated with XBCQ by intragastric administration and then twice per day. Feces of the rats were collected and the gut microbiota constituents were analyzed by 16S rDNA sequencing. Histological changes were observed by H&E staining. Occludin content in the colon was determined by immunohistochemical analysis. The concentrations of cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. The survival rate of septic rats was increased significantly at the dose of 7.56 g/Kg from 50% to 80% at 72 h. The gut microbiota richness and composition were disturbed in septic rats. XBCQ altered the gut microbiota, involving alpha diversity changes, significantly reducing the relative abundance of Bacteroidaceae and ClostridiumXI and increasing that of Firmicutes and Actinobacteria. Furthermore, the relative abundances of Lactobacillus, Butyricicoccus and Bifidobacterium were increased by XBCQ. Moreover, the gut barrier dysfunction was improved by XBCQ through restoring the impaired tight conjunction protein Occludin. The concentration of diamine oxidase was decreased, while the D-lactate level was elevated. Meanwhile, the level of myeloperoxidase (MPO) in the lung tissue of the XBCQ-treated group was reduced. Lung injury was also alleviated by decreased levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 10 (IL-10) in bronchoalveolar lavage fluids (BALFs). The relative abundance of potential microbial biomarkers in four groups significantly correlated with the concentration of inflammatory factors in BALFs. Our results suggested that XBCQ had a protective role against sepsis by modulating the gut microbiota, restoring the intestinal epithelial barrier and decreasing inflammatory responses. Image 1 [ABSTRACT FROM AUTHOR]