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Randomized controlled trials established the cardiac protection of sodium-glucose cotransporter-2 (SGLT2) inhibitors among adults with type 2 diabetes. New evidence suggests that these results could extend to people without diabetes.To evaluate the effect of SGLT2 inhibitors in patients with heart failure, regardless of the presence of type 2 diabetes.PubMed, Web of Science, Cochrane Library, and Embase (OVID interface).Eligible trials randomly assigned adults with heart failure to SGLT2 inhibitors or control.Time-to-event individual patient data were reconstructed from published Kaplan-Meier plots; time-varying risk ratios (RRs) were calculated in half-, 1-, and 2-year time frames; and anticipated absolute benefits were calculated using simple models applying relative effects to baseline risks.Sodium-glucose cotransporter-2 inhibitors reduce hospitalization for heart failure by 37% (95% CI, 25% to 47%) at 6 months, 32% (CI, 20% to 42%) at 1 year, and 26% (CI, 10% to 40%) at 2 years (all high certainty) and reduce cardiovascular death by 14% (CI, 1% to 25%) at 1 year (high certainty). Nevertheless, low-certainty evidence did not indicate protection against all-cause death, kidney disease progression, or kidney failure. Anticipated absolute benefits are greater for patients treated in the first year and for those with poorer prognoses, such as those newly diagnosed with heart failure in the hospital. In addition, SGLT2 inhibitors doubled the risk for genital infections (RR, 2.69 [CI, 1.61 to 4.52]; high certainty).Covariates were unavailable in meta-analyses with reconstructed individual patient data.Among people with heart failure, SGLT2 inhibitors reduce hospitalizations for heart failure regardless of the presence of diabetes; absolute benefits are most pronounced in first-year treatment and vary with prognostic factors. Clinicians should note the increased risk for genital infection in patients receiving SGLT2 inhibitors.1.3.5 Project for Disciplines of Excellence, West China Hospital of Sichuan University. (PROSPERO: CRD42021255544).

Liquid crystal monomers (LCMs) in liquid crystal displays (LCDs) may be released into the environment, especially in electronic waste (e-waste) recycling industrial parks with a high pollution risk. However, little has been known about the environmental release and human exposure to LCMs until now. Herein, a total of 45 LCMs were detected in LCDs of commonly used smartphones and computers by high-resolution mass spectrometry with suspect screening analysis. Fluorinated biphenyls and their analogs were the dominant LCMs. Based on available standards of the screening results and previous studies, 55 LCMs were quantified in samples from an e-waste recycling industrial park in Central China. The LCMs were frequently detected in outdoor dust (

Yanjiao Shen,1,&ast; Yuting Wang,2,&ast; Qingyang Shi,1 Lisha Hou,3 Xiaoyan Chen,4 Birong Dong,3 Qiukui Hao3,5 1Department of Guideline and Rapid Recommendation, Cochrane China Centre, MAGIC China Centre, Chinese Evidence-Based Medicine Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada; 3The Center of Gerontology and Geriatrics/National Clinical Research Center of Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Zigong Mental Health Center, Zigong, Sichuan, People’s Republic of China; 5School of Rehabilitation Science, McMaster University, Hamilton, Ontario, Canada&ast;These authors contributed equally to this workCorrespondence: Qiukui HaoThe Center of Gerontology and Geriatrics/National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, #37 Guoxue Lane, Chengdu, 610041, People’s Republic of ChinaTel/Fax +86-28-85422321Email haoqiukui@gmail.comIntroduction: To assess whether the electronic frailty index (eFI) is independently associated with all-cause mortality and chemotherapy adverse reactions among older Chinese patients with lung cancer.Methods: This is a retrospective, single-institution, chart review, and not a prospective cohort study. All patients ≥ 60 years with primary lung cancer in the West China Hospital from 2010 to 2017 were included in this cohort. The eFI was established using 35 frailty-related variables in the electronic medical record (EMR) system and was cut by a value of 0.2 to classify the patients into frail (eFI ≥ 0.2) and robust/non-frail groups (eFI< 0.2). The long-term outcome was all-cause mortality identified by government databases and telephone interviews. Short-term outcomes were any infection, bone suppression, chemotherapy discontinuation, impaired liver function, any gastrointestinal reactions and length of hospitalization. An inverse probability weighting method was used to eliminate the potential confounders. An adjusted Kaplan–Meier estimator and a weighted Cox model were used to calculate the survival and hazard ratio. A weighted logistic model was used to calculate the odds of short-term outcomes.Results: A total of 997 patients were included in this study with a median follow-up of 34 months. Compared with non-frail patients, frail patients had an increased risk of mortality and shortened overall survival (hazard ratio [HR] of mortality, 1.29; 95% confidence interval [CI], 1.05 to 1.60; adjusted restricted mean survival time [aRMST] difference, − 5.68 months; 95% CI, − 10.15 to − 1.21 months). For short-term outcomes, frail patients had increased odds of infection compared to non-frail patients (odds ratio, 1.83; 95% CI, 1.09 to 3.06). No other outcome showed a significant result.Conclusion: This study of older Chinese patients with primary lung cancer suggests that eFI-based frail patients had worse prognoses with increased risk of all-cause mortality and shortened survival times.Keywords: electronic frailty index, all-cause mortality, lung cancer

IntroductionRed meat overconsumption is an unhealthy behavior, while its attributed burden and epidemiological pattern remain unclear. This study aimed to describe the status and trend of how the diet high in red meat burdens the world.Material and methodsWe accessed the data of summary exposure values (SEVs), deaths, and disability-adjusted life of years (DALYs) with their age-standardized rates in each country from the Global Burden of Disease Collaborative Network from 1990 to 2019. We calculated estimated annual percentage changes (EAPCs) to evaluate the trends of the disease burden.ResultsThe age-standardized SEV rates increased in most of the 21 GBD regions, mainly in the low-middle and middle SDI quantiles from 1990 to 2019, while East Asia increased the most rapidly. In 2019, diet high in red meat was responsible for 0.6 million (95% uncertainty interval [UI] 0.3 to 0.8 million) deaths and 23.9 million (95% UI 15.6 to 32.0 million) DALYs worldwide. From 1990 to 2019, the total deaths and DALYs attributable to diet high in red meat have increased by over 50%. However, the age-standardized death and DALY rates decreased by 30.3% and 23.5% during the study period, respectively. The age-standardized death and DALY rates in the middle SDI regions surpassed those in the high SDI regions since 2002. Ischemic heart disease, diabetes mellitus, and colorectal cancer were the main causes of diet high in red meat-related death and DALYs.ConclusionsIncreasing consumption of red meat remains challenging the world, especially in the low-middle and middle SDI countries.

To evaluate the impact of stress hyperglycemia on the in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes.We identified non-surgical hospitalized patients with heart failure and type 2 diabetes from a large electronic medical record-based database of diabetes in China (WECODe) from 2011 to 2019. We estimated stress hyperglycemia using the stress hyperglycemia ratio (SHR) and its equation, say admission blood glucose/[(28.7 × HbA1c)- 46.7]. The primary outcomes included the composite cardiac events (combination of death during hospitalization, requiring cardiopulmonary resuscitation, cardiogenic shock, and the new episode of acute heart failure during hospitalization), major acute kidney injury (AKI stage 2 or 3), and major systemic infection.Of 2875 eligible Chinese adults, SHR showed U-shaped associations with composite cardiac events, major AKI, and major systemic infection. People with SHR in the third tertile (vs those with SHR in the second tertile) presented higher risks of composite cardiac events ([odds ratio, 95% confidence interval] 1.89, 1.26 to 2.87) and major AKI (1.86, 1.01 to 3.54). In patients with impaired kidney function at baseline, both SHR in the first and third tertiles anticipated higher risks of major AKI and major systemic infection.Both high and low SHR indicates poor prognosis during hospitalization in non-surgical patients with heart failure and type 2 diabetes.

Bifenthrin (BF) is a widely used pyrethroid that has been frequently detected in surface waters. Previous studies indicated that BF had antiestrogenic activity in zebrafish embryos but estrogenic activity in posthatch fish. To determine whether age-related differences in metabolism contribute to the endocrine effects in developing fish, embryos from zebrafish and Japanese medaka were exposed to BF before and after liver development. Since the commercial mixture of BF is an isomer-enriched product containing two enantiomers (1R-cis-BF and 1S-cis-BF), enantioselective metabolism was also evaluated. The estrogenic metabolite, 4-hydroxybifenthrin (4-OH-BF) was identified in zebrafish embryos, and formation was higher in animals after liver development (>48 hpf). Treatments with β-glucuronidase indicated that 4-OH-BF underwent conjugation in embryos. Formation was reduced by cotreatment of the cytochrome P450 (CYP450) inhibitor, ketoconazole. Formation of 4-OH-BF was greater when treated with 1R-cis-BF compared to the S-enantiomer. However, metabolites were not observed in medaka embryos. These data indicate enantioselective oxidation of BF to an estrogenic metabolite occurs in zebrafish embryos and, since it is increased after liver development, may partially explain estrogenic activity observed in older animals. The lack of activity in medaka suggests species-specific effects with BF metabolism and may influence risk assessment strategies in wildlife.

Current practice uses the latest measure of glycated hemoglobin (HbAlc) to facilitate clinical decision-making. Studies have demonstrated that HbAlc variability links the risk of death and complications of diabetes. However, the role of HbAlc variability is unclear in clinical practice. This systematic review summarized the evidence of visit-to-visit HbAlc variability regarding different metrics in micro- and macro-vascular complications and death in people with type 2 diabetes.We searched PubMed, EMBASE (via OVID), and Cochrane Central Register (CENTRAL, via OVID) for studies investigating the association between HbAlc variability and adverse outcomes in patients with type 2 diabetes and performed random-effects meta-analysis stratified by HbAlc variability metrics in terms of standard deviation (SD), coefficient of variation (CV), and HbAlc variability score (HVS).In people with type 2 diabetes, the highest quantile of all three HbAlc variability metrics (HbAlc-standard deviation [HbAlc-SD], HbAlc-coefficient of variance [HbAlc-CV], and HVS) is associated with increased risks of all-cause mortality, cardiovascular events, progression to chronic kidney disease, amputation, and peripheral neuropathy. For example, the hazard ratio of HbAlc-SD on all-cause mortality was l.89 with 95% confidence interval (95% CI) l.46-2.45 (HbAlc-CV l.47, 95% CI l.26-l.72; HVS l.67, 95% CI l.34-2.09).High HbAlc variability leads to micro- and macro-vascular complications of type 2 diabetes and related death. People with type 2 diabetes and high HbAlc variability need additional attention and care for the potential adverse outcomes.

Objective To diagnose the ring chromosome 13 (r(13)) in a fetus, and analyze the genotype–phenotype correlation. Case report A 26-year-old woman who was second pregnancy, underwent amniocentesis at 18 weeks of gestation because of the increased nuchal translucency (NT). Prenatal ultrasound showed the NT thickness was 3.5 mm at 12+1 weeks of gestation and nuchal fold (NF) was 6.1 mm at 18 weeks of gestation, and amniotic fluid karyotype analysis revealed mosaic r(13). CMA detected a 16.293 Mb duplication at 13q21.32q31.1 and 31.303 Mb deletion at 13q31.1q34. Conclusion R(13) is a very rare chromosomal abnormality. Cytogenetic examination combined with CMA can provide accurate diagnosis and effective information for genetic counseling.

Objective To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. Design Systematic review and network meta-analysis. Data sources Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. Eligibility criteria for selecting studies Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. Results The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference −8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes ( https://matchit.magicevidence.org/230125dist-diabetes ). Conclusions This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. Systematic review registration PROSPERO CRD42022325948.

Chromosomal inversion is closely related to male infertility. Inversion carriers may produce abnormal gametes, which may lead to partial duplication/deletion of the embryonic chromosome and result in spontaneous abortion, a fetus with multiple anomalies, or birth of a malformed child. Genetic counselling remains challenging for these carriers in clinical practice. We report two male carriers with inversion of chromosome 10 and review 26 reported cases. In the first case, 46,XX,inv(10)(p13q22) of the fetal chromosome was found in prenatal diagnosis; this was inherited from the paternal side with 46XY,inv(10)(p13q22). Another case was a male carrier with inv(10)(q21.2q22.1). There have been 25 (89.3%) cases of pericentric inversion and three (10.7%) cases of paracentric inversion involving chromosome 10. Of 28 cases, nine were associated with pregestational infertility of the couples, while the other 19 cases were associated with gestational infertility of the couples or normozoospermia. The breakpoints at 10p15, 10p11, 10q11, and 10q21 were associated with pregestational infertility of the couples. The breakpoints at 10p15, 10p14, 10p13, 10p12, 10p11, 10q11, 10q21, 10q22, 10q23, 10q24, 10q25, and 10q26 were related to gestational infertility of the couples or normozoospermia. Although there is a high risk of infertility or recurrent miscarriages, carriers with inversion of chromosome 10 might produce healthy offspring. Natural pregnancy can be used as a choice for inversion carriers with recurrent spontaneous abortion.

Background Trisomy 19q is a recognizable syndrome and associated with a wide spectrum of clinical phenotypes in clinic. The purpose of this study was to explore the prenatal phenotypes of 19q13.42 duplication, which was rarely reported in clinic. Case presentation Three pregnant women presenting diverse indications for prenatal diagnosis accepted amniocentesis: increased nuchal translucency and fetal pyelic separation (case 2) and high risk of maternal serum screening for Down syndrome (case 1 and case 3). Case 1 and case 2 shared similar duplicated locus in the region of 19q13.42, encompassing part NLRP12 gene. The latter inherited the chromosomal duplication from the mother with normal phenotypes. Case 3 carried a 1.445 Mb duplication in the 19q13.42q13.43 region. It was proposed that evolutionary duplication of NLRP12 gene could have a causative role in autoinflammatory diseases development. The genotype–phenotype correlation depends mainly on the duplicated size and functional genes involved, which is still yet to be determined. All pregnant women chose to continue the pregnancy and delivered healthy children with no apparent abnormalities. Conclusions The 19q13.42 microduplications in our study were the smallest fragments compared to previous literature. Our findings enriched the prenatal phenotypes for this chromosomal microscopic imbalance. It was proposed that long term follow up analysis should be guaranteed till adulthood to determine whether there will be other emerging clinical symptoms and developmental-behavioral disorders for such carriers.

BackgroundHigh low-density lipoprotein-cholesterol (LDL-C) is a public health issue contributing to ischemic heart disease (IHD) and stroke.MethodIn this ecological study, we collected summary exposure values (SEVs), deaths, disability-adjusted life of years (DALYs), and Social Demographic Index (SDI) of high LDL-C from 1990 to 2019 using the query tool from the Global Burden of Disease (GBD) Collaborative Network. Outcomes include SEVs, deaths, and DALYs attributable to high LDL-C stratified by sex, age, region, SDI, countries, and territories. Estimated annual percentage changes (EAPCs) were applied to estimate annual trends of changes in these outcomes. We applied the weighted segmented regression with break-point estimation to detect the linear piecewise relationship between SDI and high LDL-C disease burden.ResultsGlobally, 3.00 million (95% uncertainty interval [UI], 2.35–3.76 million) people in 1990 and 4.40 million (95% UI, 3.30–5.65 million) people died from high LDL-C in 2019. The absolute annual burden from deaths and DALYs attributed to high LDL-C increased by 46% (95% UI, 35–56%) and 41% (95% UI, 31–50%) from 1990 to 2019. The age-standardized SEV, death, and DALY was decreased by 9% (95% UI, −11 to −8%), 37% (95% UI, −41−33%), and 32% (95% UI, −37 to −28%), respectively, during the study period. There was a negative association between SDI and high LDL-C-related age-standardized death and DALY rates when SDI surpassed 0.71 and 0.71, respectively.ConclusionAlthough the overall age-standardized burden of high LDL-C is controlled in the past 30 years, it remains increasing in moderate SDI countries, and decreasing trends are disappearing in high SDI countries. New challenges require new actions stratified by countries with different SDI levels.

Cholesterol homeostasis is related to multiple diseases in humans, including cardiovascular disease, cancer, and neurodegenerative and hepatic diseases. The cholesterol levels in cells are balanced dynamically by uptake, biosynthesis, transport, distribution, esterification, and export. In this review, we focus on de novo cholesterol synthesis, cholesterol synthesis regulation, and intracellular cholesterol trafficking. In addition, the progression of lipid transfer proteins (LTPs) at multiple contact sites between organelles is considered.

Per- and polyfluoroalkyl substances (PFASs) are man-made persistent organic compounds of significant health and environmental concern because of their resistance to degradation, tendency for global...

Integrating reactive oxygen species (ROS)-based catalytic therapy and photothermal therapy into one single nanosystem is an inspiring therapeutic approach for tumours. Herein, multifunctional Au nanoparticles with copper–tannic acid coordination core–shell nanostructures (Au@TACu NSs) were fabricated through a one-step method. The obtained Au@TACu NSs possessed a superior hyperthermic effect for tumour ablation, as well as preferential peroxidase-like activity to induce the production of toxic hydroxyl radicals (˙OH) through the decomposition of H2O2 for oxidation therapy. Notably, the hyperthermic effect and GSH-depleting capability of Au@TACu NSs can further amplify ˙OH production, achieving photothermally-enhanced oxidation therapy (PTT/OT). Moreover, such a synergistic therapeutic strategy showed highly efficient inhibition of tumour growth in vivo with unnoticeable tissue damage. Our work provides insights into the use of Au-based nanomaterials as theranostic agents for PTT/OT synergistic tumour therapy.

BackgroundFunctional constipation (FC) is a common bowel disorder that prevails worldwide. In China, although a heterogeneous prevalence of constipation is expected, it is currently not demonstrated. In this study, we aimed to evaluate the prevalence and related risk factors of FC in the Chinese population, according to the Rome criteria.MethodsWe searched the PubMed, the Embase, the Cochrane Library, the Web of Science, the China National Knowledge Infrastructure (CNKI), the Wanfang data knowledge service platform, the VIP information resource integration service platform, and the Chinese Biomedical Literature Service System (SinoMed) databases from the inception of database to July 2021. Population-based cross-section studies that enrolled adults with FC, diagnosed by the Rome criteria, were deemed eligible. We summarized the overall prevalence and detected the subgroup effect per the Rome I, Rome II, Rome III, and Rome IV criteria. We used the generalized linear mixed model (GLMM) with a random-effect intercept to pool the prevalence and performed pairwise meta-analyses for prevalence comparisons by risk factors.ResultsWe identified 3,213 records through our database search, and 39 studies from China, comprising 1,240,79 participants, met the eligibility criteria for our study. The pooled overall prevalence of FC using the Rome criteria was 8.5% in China. Heterogeneous prevalence was detected within the Rome criteria (Rome II: 10.6%, 95% CI: 7.2–15.4; Rome III: 6.5%, 95% CI: 3.4–12.0; Rome IV: 8.1%, 95% CI: 5.6–11.8). The prevalence increased between 1991 and 2020 (from 5.5% with 95% CI: 3.6–8.2 between 1991 and 2000 to 10.9% with 95% CI: 5.5–20.4 between 2011 and 2020). Higher prevalence was found in women [odds ratio (OR) = 1.53, 95% CI: 1.31–1.78] and the elderly (≥70 years vs. ≤ 29 years: OR = 3.38, 95% CI: 2.16–5.30) than in men and the younger population. A high-fiber diet was associated with lower prevalence (OR = 0.33, 95% CI: 0.15–0.75), whereas irregular bowel habit and inactivity were associated with higher prevalence (OR = 3.64, 95% CI: 2.64–5.03; OR = 1.97, 95% CI: 1.14–3.43). Unhealthy mental states, such as anxiety and depression, and poor sleep quality led to high prevalence (OR = 3.16, 95%C I: 1.96–5.11; OR = 2.74, 95% CI: 1.76–4.26; OR = 2.14, 95% CI: 1.69–2.72, respectively).ConclusionVarious types of FC prevail in China based on the different Rome criteria, personal characteristics, and habits. The prevalence also increased over the past three decades. The FC should be included under the primary care setting with uniform diagnosis criteria in China.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, CRD42021277172.

Contaminants of emerging concern (CECs) as well as their transformation products (TPs) are often found in treated wastewater and biosolids, raising concerns about their environmental risks. Small changes in chemical structure, such as the addition or loss of a methyl group, as the result of methylation or demethylation reaction, may significantly alter a chemical's physicochemical properties. In this study, we evaluated the difference in accumulation and translocation between four CECs and their respective methylated or demethylated derivatives in plant models. Suspended Arabidopsis thaliana cell culture and wheat seedlings were cultivated in nutrient solutions containing individual compounds at 1 mg/L. The methylated counterparts were generally more hydrophobic and showed comparative or greater accumulation in both plant models. For example, after 1 h incubation, methylparaben was found in A. thaliana cells at levels two orders of magnitude greater than demethylated methylparaben. In contrast, the demethylated counterparts, especially those with the addition of a hydroxyl group after demethylation, showed decreased plant uptake and limited translocation. For example, acetaminophen and demethylated naproxen were not detected in the shoots of wheat seedlings after hydroponic exposure. Results from this study suggest that common transformations such as methylation and demethylation may affect the environmental fate of CECs, and should be considered to obtain a more comprehensive understanding of risks of CECs in the environment.

In nanocrystalline silicon carbide (NC-SiC), nanocrystalline-to-amorphous (NC-A) transformation can be induced due to atomic displacement events. To evaluate the detailed mechanisms of radiation resistance to amorphization and understand the role of grain boundaries (GBs), it is significantly critical to determine the amorphized dose of NC-SiC by inducing atomic displacements and obtain the information of defect behaviors in the NC-A transformation by using molecular dynamics methods. The results of this study revealed that full amorphization of NC-SiC was achieved by randomly displace (1) a Si atom or (2) a Si/C atom at the same dose of displacement per atom (dpa). The migration of carbon interstitial is the driving force in the amorphization process of NC-SiC according to the low migration energy of carbon in 3C-SiC. Moreover, defect clusters subsequently form and merge into the amorphous domains at the GBs, which will reveal the microscopic mechanism of the irradiation-induced NC-SiC amorphization.

Pesticide contamination is a threat to many aquatic habitats, and runoff from residential homes is a major contributor of these chemicals in urban surface streams and estuaries. Improved understanding of their fate and transport can help identify areas of concern for monitoring and management. In many urban areas, runoff water congregates in numerous underground catch basins before draining into the open environment; however, at present essentially no information is available on pesticide presence in these systems. In this study, we collected water samples from a large number of underground urban catch basins in different regions of California during the active pest management season to determine the occurrence and profile of the widely used pyrethroid insecticides. Detectable levels of pyrethroids were found in 98% of the samples, and the detection frequency of individual pyrethroids ranged from no detection for fenpropathrin to 97% for bifenthrin. In the aqueous phase, total pyrethroid concentrations ranged from 3 to 726 ng/L, with a median value of 32 ng/L. Pyrethroids were found to be enriched on suspended solids, with total concentrations ranging from 42 to 93,600 ng/g and a median value of 2,350 ng/g. In approximately 89% of the samples, whole water concentrations of bifenthrin were predicted to have toxic units1 for sensitive aquatic invertebrates. The high detection frequency of bifenthrin and overall pyrethroid concentrations, especially for particle-bound residues, suggest that underground urban catch basins constitute an important secondary source for extended and widespread contamination of downstream surface waters by pesticides such as pyrethroids in urban regions.

Background: Heart failure as an important issue in global public health, has brought a heavy economic burden. Traditional Chinese medicine injections (TCMIs) have significant effects on heart failure with reduced ejection fraction (HFrEF). However, it is difficult for clinicians to identify the differences in clinical efficacy and safety of various TCMIs. The purpose of this study is to compare the efficacy and safety of various TCMIs for treating HFrEF by conducting a Bayesian network meta-analysis (NMA) and to further provide references for clinical decision-making.Methods: The clinical randomized controlled trials of TCMIs for treating HFrEF were searched in seven database from inception to August 3rd, 2021. The Cochrane collaboration’s tool was used to assess the risk of bias. NMA was performed in a Bayesian hierarchical framework. The surface under the cumulative ranking curve (SUCRA), the multi-dimensional efficacy analysis, the comparison-adjusted funnel plot, and the node-splitting analysis were conducted using R software.Results: A total of 107 eligible RCTs involving 9,073 HFrEF patients and 6 TCMIs were included. TCMIs include Huangqi injection (HQ) also called Astragalus injection, Shenfu injection (SF), Shengmai injection (SGM), Shenmai injection (SM), Xinmailong injection (XML), and Yiqifumai lyophilized injection (YQFM). The results of NMA and SUCRA showed that with conventional treatment (CT) as a common control, in terms of clinical efficacy, CT + XML was most effective in New York Heart Association cardiac functional classification efficiency, brain natriuretic peptide, and N-terminal pro-brain natriuretic peptide; the CT + SM was most effective in 6-min walking test, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac output; the CT + YQFM was most effective in left ventricular ejection fraction; the CT + HQ was most effective in stroke volume; the CT + SF was most effective in Minnesota Living with Heart Failure Questionnaire. In terms of safety, there was no significant difference between CT + TCMIs and CT.Conclusion: This Bayesian network meta-analysis results show that the combination of qualified TCMIs and CT is more effective for HFrEF patients than CT alone, and CT + XML and CT + SM may be one of the potential optimal treatments. Also, the safety of these TCMIs needs to be further observed. However, due to some limitations, the conclusions need to be verified by more large-sample, double-blind, multi-center RCTs.

Background. Acupoint sensitization is considered an important factor in the efficacy of acupoint therapy. This study aimed to evaluate the efficacy of acupressure in the prevention of stable angina pectoris using acupoints with different pressure-pain sensitivities. Methods. A total of 202 patients were enrolled and randomly assigned to a high-sensitivity group (HSG) (n = 109) in which patients received acupressure at the five acupoints with the highest sensitivity to pain and a low-sensitivity group (LSG) (n = 93) in which patients received acupressure at the five acupoints with the lowest sensitivity to pain. The duration of acupressure treatment was 4 weeks, and the patients were evaluated at baseline, week 4, and week 8. The primary outcome was a change in the frequency of angina attacks from baseline. The secondary outcomes included nitroglycerin consumption, the Canadian Cardiovascular Society classification, and the Seattle Angina Questionnaire score. Adverse events such as bleeding and subcutaneous haemorrhage were recorded in both groups. Results. The effect of acupressure compared with baseline on the prevention of angina pectoris in HSG was better than that in LSG at week 4 (incidence rate ratio (IRR): 0.691 and 95% confidence interval (CI): [0.569, 0.839]) and week 8 (IRR: 0.692 and 95% CI: [0.569, 0.839]). No significant difference between groups was found in the frequency of nitroglycerin consumption at week 4 (odds ratio (OR) = 0.863 and 95% CI: [0.147, 5.077]) or week 8 (OR = 1.426 and 95% CI: [0.211, 9.661]). Two themes in the questionnaire showed significantly different changes from baseline between the two groups. Scores on the angina frequency (AF) subscale had changed more from the baseline in the HSG at week 8 than in the LSG (mean difference (MD) = 3.807 and 95% CI: [0.673, 6.942]). Scores on the treatment satisfaction (TS) subscale had also changed more in the HSG than in the LSG at week 4 (MD = 3.651 and 95% CI: [0.327, 7.327]) and week 8 (MD = 4.220 and 95% CI: [0.347, 7.346]). One patient in the LSG reported bruising at the acupoint. No unexpected safety problems arose. Conclusions. This study showed that acupressure at acupoints with high sensitivity to pain may effectively reduce the frequency of stable angina pectoris episodes. This trial is registered with NCT03975140.

Tumor microenvironment–responsive polypeptide nanogels belong to a biomaterial with excellent biocompatibility, easily adjustable performance, biodegradability, and non-toxic properties. They are developed for selective delivery of antitumor drugs into target organs to promote tumor cell uptake, which has become an effective measure of tumor treatment. Endogenous (such as reduction, reactive oxygen species, pH, and enzyme) and exogenous (such as light and temperature) responsive nanogels can release drugs in response to tumor tissues or cells to improve drug distribution and reduce drug side effects. This article systematically introduces the research progress in tumor microenvironment–responsive polypeptide nanogels to deliver antitumor drugs and provides a reference for the development of antitumor nanoformulations.

In the present study, we investigated the dopaminergic and steroid hormone systems of A/J mice fed environmentally relevant concentrations of a perfluoroalkyl substance (PFAS) mixture over a period of 10 weeks. The PFAS mixture was chosen based on measured PFAS concentrations in earthworms at a Norwegian skiing area (Trondheim) and consisted of eight different PFAS. Dietary exposure to PFAS led to lower total brain dopamine (DA) concentrations in male mice, as compared to control. On the transcript level, brain tyrosine hydroxylase (th) of PFAS exposed males was reduced, compared to the control group. No significant differences were observed on the transcript levels of enzymes responsible for DA metabolism, namely – monoamine oxidase (maoa and maob) and catechol-O methyltransferase (comt). We detected increased transcript level for DA receptor 2 (dr2) in PFAS exposed females, while expression of DA receptor 1 (dr1), DA transporter (dat) and vesicular monoamine transporter (vmat) were not affected by PFAS exposure. Regarding the steroid hormones, plasma and muscle testosterone (T), 11-ketotestosterone (11-KT) and 17β-estradiol (E2) levels, as well as transcripts for estrogen receptors (esr1 and esr2), gonadotropin releasing hormone (gnrh) and aromatase (cyp19) were unaltered by the PFAS treatment. These results indicate that exposure to PFAS doses, comparable to previous observation in earthworms at a Norwegian skiing area, may alter the dopaminergic system of mice with overt consequences for health, general physiology, cognitive behavior, reproduction and metabolism.

Our aim was to investigate the association of glycated haemoglobin A1c (HbA1c) variability score (HVS) with estimated glomerular filtration rate (eGFR) slope in Chinese adults living with type 2 diabetes. This cohort study included adults with type 2 diabetes attending outpatient clinics between 2011 and 2019 from a large electronic medical record-based database of diabetes in China (WECODe). We estimated the individual-level visit-to-visit HbA1c variability using HVS, a proportion of changes in HbA1c of ≥0.5% (5.5 mmol/mol). We estimated the odds of people experiencing a rapid eGFR annual decline using a logistic regression and differences across HVS categories in the mean eGFR slope using a mixed-effect model. The analysis involved 2397 individuals and a median follow-up of 4.7 years. Compared with people with HVS ≤ 20%, those with HVS of 60% to 80% had 11% higher odds of experiencing rapid eGFR annual decline, with an extra eGFR decline of 0.93 mL/min/1.73 m2 per year on average; those with HVS > 80% showed 26% higher odds of experiencing a rapid eGFR annual decline, with an extra decline of 1.83 mL/min/1.73 m2 per year on average. Chinese adults with type 2 diabetes and HVS > 60% could experience a more rapid eGFR decline.

BackgroundDiabetes is prevalent worldwide including hospitalized patients with heart failure with reduced ejection fraction (HFrEF). This retrospective study investigated the association of diabetes with in-hospital adverse events in patients with HFrEF.MethodsWe analyzed data from electronic medical records of patients hospitalized with HFrEF in West China Hospital of Sichuan University from January 1, 2011, to September 30, 2018. Propensity score matching balances the baseline characteristics between patients with and without diabetes. Logistic and Poisson regressions investigated the association of diabetes with risks of intubation, cardiogenic shock, acute kidney injury (AKI), intensive care unit (ICU) admission and death during hospitalization, and length of ICU and hospital stay in the matched cases.ResultsAmong 6,022 eligible patients (including 1,998 with diabetes), 1,930 patient pairs with and without diabetes were included by propensity score matching. Patients with diabetes had a significantly increased risk of intubation (odds ratio [OR], 2.69; 95% confidence interval [CI], 2.25–3.22; PPPPPPPConclusionsAmong patients with HFrEF, those with diabetes have a worse prognosis, including a higher risk of in-hospital intubation, cardiogenic shock, AKI, ICU admission and death during hospitalization, and longer ICU and hospital stay.

Recycled water (RW) has been increasingly recognized as a valuable source of water for alleviating the global water crisis. When RW is used for agricultural irrigation, many contaminants of emerging concern (CECs) are introduced into the agroecosystem. The ubiquity of CECs in field soil, combined with the toxic, carcinogenic, or endocrine-disrupting nature of some CECs, raises significant concerns over their potential risks to the environment and human health. Understanding such risks and delineating the fate processes of CECs in the water-soil-plant continuum contributes to the safe reuse of RW in agriculture. This review summarizes recent findings and provides an overview of CECs in the water-soil-plant continuum, including their occurrence in RW and irrigated soil, fate processes in agricultural soil, offsite transport including runoff and leaching, and plant uptake, metabolism, and accumulation. The potential ecological and human health risks of CECs are also discussed. Studies to date have shown limited accumulation of CECs in irrigated soils and plants, which may be attributed to multiple attenuation processes in the rhizosphere and plant, suggesting minimal health risks from RW-fed food crops. However, our collective understanding of CECs is rather limited and knowledge of their offsite movement and plant accumulation is particularly scarce for field conditions. Given a large number of CECs and their occurrence at trace levels, it is urgent to develop strategies to prioritize CECs so that future research efforts are focused on CECs with elevated risks for offsite contamination or plant accumulation. Irrigating specific crops such as feed crops and fruit trees may be a viable option to further minimize potential plant accumulation under field conditions. To promote the beneficial reuse of RW in agriculture, it is essential to understand the human health and ecological risks imposed by CEC mixtures and metabolites.

Bifenthrin (BF) is a widely used pyrethroid that has been frequently detected in surface waters. Previous studies indicated that BF had antiestrogenic activity in zebrafish embryos but estrogenic activity in posthatch fish. To determine whether age-related differences in metabolism contribute to the endocrine effects in developing fish, embryos from zebrafish and Japanese medaka were exposed to BF before and after liver development. Since the commercial mixture of BF is an isomer-enriched product containing two enantiomers (1

Background: Hyperuricemia is a common metabolic disease and has become a public health problem because of its increasing prevalence and association with comorbidities. Allopurinol and febuxostat are recommended as the first-line treatments for hyperuricemia and gout. But cardiovascular safety between febuxostat and allopurinol is still controversial. The purpose of this study is to compare the cardiovascular safety of XOIs and placebo in hyperuricemic patients with or without gout.Methods: PubMed, Embase via OVID, Cochrane Library, CNKI, Wanfang, and VIP were searched from their earliest records to February 8th 2021. ClinicalTrials.gov was also searched for unpublished data. The reference lists of included studies and relevant review articles investigating the cardiovascular safety of XOIs in hyperuricemia patients are screened for potentially eligible studies. Randomized controlled trials (RCTs) evaluating allopurinol (100~900 mg/d), febuxostat (20~120 mg/d), or placebo for hyperuricemia were included. The outcomes were incidence of MACE, non-fatal MI, non-fatal stroke, and cardiovascular death. We conducted a Bayesian random-effects network meta-analysis on the included randomized controlled trials using the Markov Chain Monte Carlo simulation method. The grading of recommendations assessment, development, and evaluation (GRADE) approach was used to assesses the certainty of the evidence.Results: Ten RCTs with 18,004 participants were included. The network estimates showed that there was no significant difference observed among febuxostat, allopurinol, and placebo regarding outcomes. The certainty of the evidence ranged from very low to moderate. The probabilities of rankings and SUCRA showed that compared to placebo, febuxostat, and allopurinol might prevent adverse cardiovascular events.Conclusion: Febuxostat is not associated with increasing risk of adverse cardiovascular events compared to allopurinol; and compared to placebo, whether febuxostat and allopurinol reduce the risk of adverse cardiovascular events remains uncertain.

Background To provide evidence for medical management of chronic idiopathic constipation (CIC) in China based on comparisons of all clinical practical interventions using Bayesian network meta-analysis. Methods We conducted a systematic literature review by searching PubMed, Embase, Cochrane Central, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database (inception to May 2019) for randomized controlled trials (RCTs) for CIC in Chinese people. Only RCTs that recruited participants aged over 18 and diagnosed with CIC by the Rome II, III or IV criteria were included. We used three outcomes to examine efficacy. The risk ratio (RR) of the responder rate, based on ≥3 spontaneous bowel movements (SBMs) per week after treatment, was the primary outcome, and the SBM count per week and the Bristol score (BS) were secondary outcomes. In addition, adverse effects (AEs) were also considered a secondary outcome to evaluate safety. We conducted Bayesian network meta-analysis with random effects, and the RR or mean difference with its 95% credible interval was calculated. In addition, we ranked all treatments via their cumulative curves (SUCRA) and assessed the quality of evidence according to the GRADE criteria. Results We included a total of 42 trials (6820 participants) of 20 grouped interventions that included pharmacological and nonpharmacological treatments. For the primary outcome, fourteen interventions were significantly better than placebo, and Probiotics plus Mosapride (PB + MP) appeared superior to others (GRADE quality of evidence: Moderate to Low), followed by Prucalopride (PP) (High to Low) and Electroacupuncture (EA) (High to Low). For SBM, Compound sodium bicarbonate suppository (CSBS) appeared to be best, with an SUCRA value of 90% (High to Low). For BS, Lactulose plus Probiotics (LT + PB) was superior to others (Moderate to Low), followed by Polyethylene glycol (PEG) (High to Moderate). Although all interventions appeared non-significant when compared with placebo in terms of adverse effects, Lactulose plus Mosapride showed greater risk than others on ranking probability. Conclusions Given the GRADE assessment, PB + MP, PP and EA may be the priory options with moderate certainty in the quality of evidence for the primary outcome. For SBM, a CSBS may be the best option with moderate certainty in the quality of evidence. For BS, PEG may be the priory option with high certainty in the quality of evidence. However, due to a lack of high certainty in the quality of evidence, caution is needed when recommending the interventions. Because of the limitations, an increased number of trials are required for more accurate results.

Polycystic ovary syndrome (PCOS) is a set of symptoms caused by elevated androgens (male hormones) in females. PCOS is the most common endocrine disorder among women between 18 and 44 years. Currently, the pathogenesis of PCOS remains unclear. Liquid chromatography-mass spectrometry (LC/MS)-based metabolomics is becoming more and more useful for medical research, especially in revealing the mechanism of the disease. The aim of this study was to investigate the difference of serum metabolic profiles in patients with PCOS and healthy control to better understand the mechanism of this disease. Ten patients with PCOS and 10 healthy people were recruited for this study. The serum samples were collected for LC/MS analysis. Multivariate statistical analysis was performed to discover and identify the potential biomarkers. Six biomarkers were found and identified. The biomarkers belonged to different metabolic pathway including lipid metabolism, carnitine metabolism, androgen metabolism, and bile acid metabolism. Those biomarkers also played different roles in disease progression. Metabolomics is a powerful tool used in research of the mechanism involved in this disease to provide useful information for better understanding of PCOS.

Background:Mycoplasma pneumoniae pneumonia (MPP) causes flu-like symptoms in children, increasing the burden on the health and education systems. In China, traditional Chinese medicine oral liquids (TCMOLs) combined with azithromycin (TCMOLs + Azithromycin) is commonly used to treat MPP in children. However, TCMOLs with the optimal clinical applicability remain unknown. Here, we evaluated the clinical effectiveness and safety of TCMOLs + Azithromycin in children with MPP.Methods: We searched PubMed, Embase, Cochrane Library, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP information resource integration service platform databases for eligible randomized controlled trials (RCTs) published from database inception to October 2020. Two reviewers independently performed data extraction and risk of bias assessment. After Bayesian random effect modeling and surface under the cumulative ranking curve (SUCRA) scoring, we ranked each intervention. We assessed heterogeneity using multivariate meta-regression for potential modifiers and used the Grading of Recommendations, Assessment, Development, and Evaluation to rate pooled evidence’s certainty.Results: In the 63 included RCTs with 6,410 children, five different TCMOLs were combined with azithromycin. TCMOLs + Azithromycin had significantly better primary outcomes than did azithromycin alone. Of all TCMOLs, Xiaoer Xiaoji Zhike (XEXJZK)+Azithromycin showed the best effectiveness with respect to the response rate (odds ratio [OR] = 6.5, 95% credible interval [CrI] = 4.3–10; low certainty) and pulmonary rales disappearance time (mean difference [MD] = −2.1, 95% CrI: −2.9 to −1.2; low certainty) with SUCRA 85 and 80%, respectively. Pudilan Xiaoyan + Azithromycin showed the highest effectiveness with respect to cough disappearance time (MD = −2.6, 95% CrI: −3.4 to −1.7; very low certainty) and fever disappearance time (MD = −1.8, 95% CrI: −2.3 to −1.3; very low certainty) with SUCRA 87 and 87%, respectively. The difference in the adverse effects between TCMOLs + Azithromycin and azithromycin alone was nonsignificant.Conclusion: Of the different TCMOLs, XEXJZK may be the best option to combine with azithromycin to treat children with MPP. However, our results should be interpreted with caution due to the low certainty of evidence. In general, TCMOLs’ safety remains unclear because of a lack of evidence. More high-quality RCTs are needed to further evaluate efficacy and safety of these TCMOLs.

BackgroundSodium-glucose-cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control and lowering body weight in patients with type 2 diabetes mellitus. However, the efficacy and safety on weight loss in adults with overweight or obesity but not diabetes remain unclear. In this article, we aimed to identify the efficacy and safety of SGLT2 inhibitors in adults with overweight or obesity but not diabetes in randomized controlled studies (RCTs).MethodsWe searched for RCTs concerning SGLT2 inhibitors in adults with overweight or obesity but not diabetes in Medline (Ovid SP), Embase (Ovid SP), Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov up to February 2021. The primary outcomes were changes in body weight and body mass index (BMI). Trial sequential analysis (TSA) was used to test the reliability of the primary outcomes. We analyzed the data using Review Manager 5.3 and pooled data to calculate the mean differences (MDs) or the relative risk (RR). We assessed the evidence quality of evidence of outcomes according to GRADE.ResultsSix randomized controlled trials involving 872 individuals were included in the meta-analysis. Compared to the placebo group, the SGLT2 inhibitors group had statistically significant reductions in absolute changes in body weight (MD: -1.42 kg, 95% CI: -1.70 to -1.14; PConclusionSGLT2 inhibitors could be used in selected adults with overweight and obesity but not diabetes if they are at low risk of genital infection and urinary infection. Further studies are warranted to confirm the efficacy and safety of SGLT2 inhibitors in adults with overweight or obesity but not diabetes for long-term weight management.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/#loginpage], identifier [PROSPERO, CRD42021252931]

Background: Metformin, a commonly used antidiabetic medication, is available in both an immediate-release (IR) formulation and a long-acting formulation (metformin extended-release; XR).Objective: We performed a systematic review to compare the effectiveness, safety, and patient compliance and satisfaction between the metformin IR and XR formulations.Method: We searched for randomized control trials (RCTs) and observational studies comparing the effectiveness, safety, or patient compliance and satisfaction of metformin XR with metformin IR using the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Following report screening, data collection, and risk of bias assessment, we separately pooled data from RCTs and observational studies using the Grading of Recommendation Assessment, Development, and Evaluation approach to rate the quality of evidence.Result: We included five RCTs, comprising a total of 1,662 patients, and one observational study, comprising 10,909 patients. In the meta-analyses, no differences were identified in outcomes of effectiveness and safety between the two forms of metformin (including change in HbA1c: mean difference (MD), 0.04%, 95% confidence interval [CI], −0.05–0.13%, fasting blood glucose: MD, −0.03 mmol/L, 95% CI, −0.22–0.15 mmol/L, postprandial blood glucose: MD, 0.50 mmol/L, 95% CI, −0.71–1.72 mmol/L, adverse events of abdominal pain: relative risk (RR), 1.15, 95% CI, 0.57–2.33, all-cause death (RR, 3.02, 95% CI 0.12–73.85), any adverse events (RR, 1.14, 95% CI 0.97–1.34), any adverse events leading to treatment discontinuation: RR, 1.51, 95% CI, 0.82–2.8, any gastrointestinal adverse events: RR, 1.09, 95% CI, 0.93–1.29, diarrhea: RR, 0.82, 95% CI, 0.53–1.27, flatulence: RR, 0.43, 95% CI, 0.15–1.23, nausea: RR, 0.97, 95% CI, 0.64–1.47, severe adverse events: RR, 0.64, 95% CI, 0.28–1.42, and vomiting: RR, 1.46, 95% CI, 0.6–3.56). Data from both the RCTs and the observational study indicate mildly superior patient compliance with metformin XR use compared with metformin IR use; this result was attributable to the preference for once-daily administration with metformin XR.Conclusion: Our systematic review indicates that metformin XR and IR formulations have similar effectiveness and safety, but that metformin XR is associated with improved compliance to treatment.

Background: Low-density lipoprotein cholesterol (LDL-C) is a critical surrogate outcome for cardiovascular disease (CVD). Recent observational studies identified different predictive lipid parameters, but these have not been fully validated in the Chinese population. This study aimed to compare the predictive value of lipid parameters for cardiovascular outcomes in Chinese statin-naïve patients who underwent percutaneous coronary intervention (PCI).Methods: We retrospectively recruited statin-naïve patients who underwent PCI for stable angina and acute coronary syndrome at Sichuan Provincial People's Hospital between 1 January 2016 and 31 December 2017. A follow-up was conducted via outpatient visits or telephone. We divided patients into three groups based on lipid parameter tertiles. We calculated the hazard ratios (HRs) of the highest and lowest tertiles for major adverse cardiovascular events (MACEs) using multivariate Cox proportional hazards regression. We compared the association strength of lipid parameters with MACEs using the HR of non-LDL-C lipid parameters relative to LDL-C.Results: Among 445 included patients, the highest LDL-C, LDL-C/high-density lipoprotein cholesterol (HDL-C), atherosclerosis index, and non-HDL-C level tertiles were associated with an average increase of 165% (HR 2.65, confidence interval [CI] 1.26 to 5.61; P = 0.01), 324% (HR 4.24, CI 1.89 to 9.52; P < 0.001), 152% (HR 2.52, CI 1.22 to 5.22; P = 0.01), and 125% (HR 2.25, CI 1.09 to 4.64; P = 0.01) in the hazard of composite CVD, respectively. Lipoprotein (a) levels did not show a significant association with the endpoints. Except for LDL-C/HDL-C, different lipid parameter HR ratios were Conclusion: Compared with non-LDL-C lipid parameters, LDL-C acts better predictive value for cardiovascular outcomes in general Chinese statin-naïve post-PCI patients.

Background: Pharmacotherapy provides an option for overweight and obese adults to reduce their body weight if lifestyle modification fails. This systematic review summarises latest and likely practice-changing evidence for the benefits and harms of weight-lowering drugs. Methods: The network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) for randomised controlled trials of weight-lowering drugs in overweight and obese adults. We performed a frequentist random-effect network meta-analysis to summarise the evidence and applied GRADE frameworks to rate the certainty of the evidence, calculate the absolute effects, categorise interventions and present the findings. Findings: The 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered body weight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification alone. High to moderate certainty evidence established phentermine/topiramate (odds ratio [OR] of ≥5% weight reduction: 8·00, 95% confidence interval [CI]: 5·19 to 12·34; mean difference [MD] of percent body weight change: −7·97%, 95%CI: −9·28 to −6·66%) and glucagon-like peptide-1 (GLP-1) receptor agonists (OR: 6·20, 95% CI: 4·88 to 7·89; MD: −5·75%, 95%CI: −6·30 to −5·20%) were among the most effective in lowering weight. Naltrexone/bupropion (OR: 2·68, 95% CI: 2·06 to 3·49), phentermine/topiramate (OR, 2·36, 95% CI: 1·60 to 3·46), GLP-1 receptor agonists (OR: 2·16, 95% CI: 1·68 to 2·78), and orlistat (OR: 1·68, 95% CI: 1·38 to 2·05) increase any adverse event leading to drug discontinuation. In a post hoc analysis, semaglutide, one of the GLP-1 receptor agonists, demonstrated for both likelihood of ≥5% weight loss (OR: 9·81, 95% CI: 7·06 to 13·63) and percent body weight change (MD: −11.41%, 95%CI: −12.54 to −10.27%) and substantially larger than any other drugs with an increased risk of adverse events leading to discontinuation (OR: 1·98; 95% CI: 1·33 to 2·96). Interpretation: In overweight and obese adults, phentermine/topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide may be the most effective. Funding: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant numbers ZYGD18022 and 2020HXF011). Declaration of Interest: We declare no competing interests.

Acne has several effects on physical symptoms, but the main impacts are on the quality of life, which can be improved by treatment. There are several acne treatments but less evidence comparing their relative efficacy. Thus, we assessed the comparative efficacy of pharmacological and nonpharmacological interventions for acne. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to April 2019, to include randomized controlled trials for acne that compared topical antibiotics (TA), benzoyl peroxide (BPO), topical retinoids (TR), oral antibiotics (OA), lasers, light devices including LED device (LED), photodynamic therapy (PDT), and intense pulsed light, chemical peels (CP), miscellaneous therapies or complementary and alternative medicine (MTCAM), or their combinations. We performed Bayesian network meta-analysis with random effects for all treatments compared with placebo and each other. Mean differences (MDs) of lesions count and risk ratios of adverse events with their 95% credible intervals (CrIs) were calculated, and all interventions were ranked by the Surface Under the Cumulative Ranking (SUCRA) values. Additional frequentist additive network meta-analysis was performed to detect the robustness of results and potential interaction effects. Sensitivity analyses were carried out with different priors, and metaregression was to adjust for nine potential effect modifiers. In the result, seventy-three randomized controlled trials (27,745 patients with mild to moderate acne), comparing 30 grouped intervention categories, were included with low to moderate risk of bias. For adverse effects, OA had more risk in combination treatment with others. For noninflammatory lesions reduction, seventeen interventions had significant differences comparing with placebo and three interventions (TR+BPO: MD = −21.89, 95%CrI [−28.97, −14.76]; TR+BPO+MTCAM: −22.48 [−34.13, −10.70]; TA+BPO+CP: −20.63 [−33.97, −7.13]) were superior to others with 94, 94, and 91% SUCRA values, respectively. For inflammatory lesions reduction, nineteen interventions were significantly better than placebo, and three interventions (TR+BPO: MD = −12.13, 95%CrI [−18.41, −5.80]; TR+BPO+MTCAM: −13.21 [−.39, −3.04]; LED: −11.30 [−18.34, −4.42]) were superior to others (SUCRA: 81, 81, and 77%, respectively). In summary of noninflammatory and inflammatory lesions results, TR+BPO and TA+BPO were the best options compared to others. The frequentist model showed similar results as above. In summary, current evidence supports the suggestion that TR+BPO and TA+BPO are the best options for mild to moderate acne. LED is another option for inflammatory lesions when drug resistance occurs. All the combinations involved with OA showed more risk of adverse events than others. However, the evidence of this study should be cautiously used due to the limitations.

BackgroundTrisomy 19q is a recognizable syndrome and associated with a wide spectrum of clinical phenotypes in clinic. The purpose of this study was to explore the prenatal phenotypes of 19q13.42 duplication, which was rarely reported in clinic. Case presentationThree pregnant women presenting diverse indications for prenatal diagnosis accepted amniocentesis: increased nuchal translucency (case 2) and high risk of trisomy 21 (case 1 and case 3). Case 1 and case 2 shared similar duplicated locus in the region of 19q13.42, encompassing part NLRP12 gene. Case 2 inherited the chromosomal duplication from the mother with normal phenotypes. Case 3 carried a 1.445Mb duplication in the 19q13.42q13.43 region. It was proposed that evolutionary duplication of NLRP12 gene could have a causative role in autoinflammatory diseases development. The genotype-phenotype correlation depends mainly on the duplicated size and functional genes involved, which is still yet to be determined. All pregnant women chose to continue the pregnancy and delivered healthy children with no apparent abnormalities.ConclusionsThe 19q13.42 microduplications in our study are the smallest fragments compared to previous literature. We delineated 19q duplication cases without structural ultrasound anomalies for the first time, which enriched the prenatal phenotypes of this chromosomal aberration. It was proposed that long term follow up analysis should be guaranteed till adulthood to determine whether there will be other emerging clinical symptoms and developmental-behavioral disorders for such carriers.

Background: Along with the discovery of cell-free DNA (cfDNA) and the invention of next-generation sequencing (NGS), non-invasive prenatal testing (NIPT) had appeared and been applied for detecting common aneuploidies such as trisomy 21, 18, and 13, with low false-negative and false-positive rates. Recently, it had also been used for sex chromosome aneuploidies (SCAs). To assess the clinical utility of NIPT for SCAs in Northeast China, we collected NIPT data from BGI 500 sequencing platform in the Center for Reproductive Medicine, Center for Prenatal Diagnosis of the First Hospital of Jilin University, and calculate the positive predictive value (PPV) and false positive rate (FPR). Results: A cohort of 14936 samples were analyzed by NIPT, and revealed 70 cases with SCAs high-risk, among them, 40 women agreed to undergo amniocentesis, but as many as 30 ones refused further diagnose. Based on verified fetal karyotype, 30.0% (12/40) were confirmed to be a true positive. Unluckily, the PPV for monosomy X performed 0%. Besides, positive 47,XXX were 46.67% (7/15), 40.00% (2/5) were positive for 47, XYY, and 42.86% (3/7) were positive for 47, XXY.Conclusions: In conclusion, our present results confirmed that NIPT sequenced by BGI 500 demonstrated lowest PPVs for 45,X, but the more accurate prediction for other SCAs, it is still a potential method for SCAs screening. Henceforth, we should focus on how to improve the test utility and provide better services for pregnant women in need.

Background Trisomy of the short arm of chromosome 17 is a rare genomic disorder. The clinical features of complete trisomy 17p syndrome have been described. Most cases of this syndrome have been found in infants and children, but only a few cases were found by ultrasound in the prenatal period. Methods We report a case of complete trisomy 17p syndrome, which was inherited from paternal balanced translocation t(15;17)(q11.2;q11.2). A pregnant woman underwent an ultrasound examination at 24 weeks of gestation. Amniotic fluid was collected by amniocentesis. Cytogenetic and single nucleotide polymorphism array analyses were performed. We further reviewed the relationship between duplication regions and the clinical phenotype. Results Ultrasonographic evaluation showed intrauterine growth retardation and a right choroid plexus cyst, but the gallbladder was not observed. The fetal karyotype was 46,XX,der(17)t(15;17)(q11.2;q11.2)pat. The father's karyotype was 46,XY,t(15;17)(q11.2;q11.2). The single nucleotide polymorphism array results showed arr[GRCh37] 17p13.3q11.1(525‐25309337)×3, which indicated a 25.309‐Mb duplication. Conclusion Complete trisomy 17p syndrome shows severe malformations. Intrauterine growth retardation is the most typical manifestation of this syndrome as shown by ultrasonography in the second trimester of pregnancy. The genotype‐phenotype relationships of complete trisomy 17p syndrome are not completely consistent. To further determine these relationships, additional cases are necessary to provide more information from ultrasonographic findings during pregnancy.