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Objective Methods Results Interpretation The objective of this study was to investigate the association between developmental and premorbid body composition measurements and the risk of motor neuron disease (MND).We performed a cohort study in the UK Biobank to assess the association of developmental body metrics and premorbid body composition measures (using 28 measurements and 7 patterns of body composition) with the risk of MND. Among participants with longitudinal measures, we compared the changes in body composition over time between individuals who later developed MND and those who remained free of MND.Among the 412,691 individuals included in this study, 549 people received an MND diagnosis during the follow‐up visit. Higher birth weight was associated with an increased risk of MND among individuals born over 4 kg (hazard ratio [HR] per kg increase = 2.21, 95% confidence interval [CI] = 1.38–3.55), and taller adult height was associated with an increased risk of MND (HR per 5 cm increase = 1.10, 95% CI = 1.03–1.17). We observed that measures of elevated fat mass were associated with a lower risk of MND more than 5 years before diagnosis. A higher “leg‐dominant fat distribution” pattern was associated with an increased risk whereas higher “muscle strength” was associated with a reduced risk of MND 5 years before diagnosis. Longitudinal analyses indicated a faster decline in measures of fat mass and muscle strength, as well as a shift in fat distribution from arm to leg dominant, among individuals who later developed MND, compared with others.Body composition at early and middle age may be indicative of the risk of MND development. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

• This matched cohort study included 14,620 individuals with audiometry-determined objective hearing loss and 38,479 with subjective hearing loss, together with 29,240 and 38,479 matched unexposed individuals, respectively. • We found both undiagnosed objective and subjective hearing loss were associated with multiple subsequent adverse health consequences, but with discrepancies in comorbidity patterns. • Objective hearing loss had pronounced associations with neurodegenerative disease. • These findings highlight the importance of screening for speech-in-noise hearing impairment in the middle-aged population, for potential early diagnosis and intervention. Hearing impairment is common in the middle-aged population but remains largely undiagnosed and untreated. The knowledge about to what extent and how hearing impairment matters for health is currently lacking. Thus, we aimed to comprehensively examine the adverse health consequences as well as the comorbidity patterns of undiagnosed hearing loss. Based on the prospective cohort of the UK Biobank, we included 14,620 individuals (median age 61 years) with audiometry-determined (i.e., speech-in-noise test) objective hearing loss and 38,479 individuals with subjective hearing loss (i.e., tested negative but with self-reported hearing problems; median age 58 years) at recruitment (2006–2010), together with 29,240 and 38,479 matched unexposed individuals respectively. Cox regression was used to determine the associations of both hearing-loss exposures with the risk of 499 medical conditions and 14 cause-specific deaths, adjusting for ethnicity, annual household income, smoking and alcohol intake, exposure to working noise, and BMI. Comorbidity patterns following both exposures were visualized by comorbidity modules (i.e., sets of connected diseases) identified in the comorbidity network analyses. During a median follow-up of 9 years, 28 medical conditions and mortality related to nervous system disease showed significant associations with prior objective hearing loss. Subsequently, the comorbidity network identified four comorbidity modules (i.e., neurodegenerative, respiratory, psychiatric, and cardiometabolic diseases), with the most pronounced association noted for the module related to neurodegenerative diseases (meta-hazard ratio [HR] = 2.00, 95%confidence interval [CI] 1.67–2.39). For subjective hearing loss, we found 57 associated medical conditions, which were partitioned into four modules (i.e., diseases related to the digestive, psychiatric, inflammatory, and cardiometabolic systems), with meta-HRs varying from 1.17 to 1.25. Undiagnosed hearing loss captured by screening could identify individuals with at greater risk of multiple adverse health consequences, highlighting the importance of screening for speech-in-noise hearing impairment in the middle-aged population, for potential early diagnosis and intervention. [ABSTRACT FROM AUTHOR]

Background: People with intermediate hyperglycemia (IH), including impaired fasting glucose and/or impaired glucose tolerance, are at higher risk of developing type 2 diabetes (T2D) than those with normoglycemia. We aimed to evaluate the performance of published T2D risk prediction models in Chinese people with IH to inform them about the choice of primary diabetes prevention measures. Methods: A systematic literature search was conducted to identify Asian-derived T2D risk prediction models, which were eligible if they were built on a prospective cohort of Asian adults without diabetes at baseline and utilized routinely-available variables to predict future risk of T2D. These Asian-derived and five prespecified non-Asian derived T2D risk prediction models were divided into BASIC (clinical variables only) and EXTENDED (plus laboratory variables) versions, with validation performed on them in three prospective Chinese IH cohorts: ACE (n = 3241), Luzhou (n = 1333), and TCLSIH (n = 1702). Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer–Lemeshow test). Results: Forty-four Asian and five non-Asian studies comprising 21 BASIC and 46 EXTENDED T2D risk prediction models for validation were identified. The majority were at high (n = 43, 87.8%) or unclear (n = 3, 6.1%) risk of bias, while only three studies (6.1%) were scored at low risk of bias. BASIC models showed poor-to-moderate discrimination with C-statistics 0.52–0.60, 0.50–0.59, and 0.50–0.64 in the ACE, Luzhou, and TCLSIH cohorts respectively. EXTENDED models showed poor-to-acceptable discrimination with C-statistics 0.54–0.73, 0.52–0.67, and 0.59–0.78 respectively. Fifteen BASIC and 40 EXTENDED models showed poor calibration (P < 0.05), overpredicting or underestimating the observed diabetes risk. Most recalibrated models showed improved calibration but modestly-to-severely overestimated diabetes risk in the three cohorts. The NAVIGATOR model showed the best discrimination in the three cohorts but had poor calibration (P < 0.05). Conclusions: In Chinese people with IH, previously published BASIC models to predict T2D did not exhibit good discrimination or calibration. Several EXTENDED models performed better, but a robust Chinese T2D risk prediction tool in people with IH remains a major unmet need. [ABSTRACT FROM AUTHOR]

The Bi2MO4Cl (M = Gd and Nd) nanosheets were prepared by a molten salt flux method for the first time. The resulted Bi2GdO4Cl (F-BG) nanosheets showed the highest photocatalytic activity for oxygen (O2) evolution and trypan blue (TB) degradation than Bi2NdO4Cl (F-BN), Bi2GdO4Cl (S-BG) and Bi2NdO4Cl (S-BN) synthesized by a solid-state method. The F-BG nanosheets showed the larger specific surface areas and abundant pores, which could provide more reactive sites. The photoelectrochemical and photoluminescence (PL) results revealed that F-BG sample had the excellent separation and transfer rates of photogenerated charge carriers, leading to the highly photocatalytic performance for both O2 evolution and TB degradation. The UV–Vis diffuse reflectance spectra (DRS) showed all samples had the visible-light-responsive characteristic. The radical trapping experiment revealed hole (h+) played a major role, while superoxide radical ( · O 2 - ) contributed a little to photocatalytic degradation process. Thus, a possible photocatalytic mechanism was proposed based on the radical trapping experiment. This work shows us a useful insight into the preparation of highly active bismuth-based oxyhalide nanosheets photocatalysts by a molten salt synthesis through surface modification and morphology control and provides the possibility of water splitting under visible light. [ABSTRACT FROM AUTHOR]

Aims: Robust diabetes risk estimates in Asian patients with impaired glucose tolerance (IGT) and coronary heart disease (CHD) are lacking. We developed a Chinese type 2 diabetes risk calculator using Acarbose Cardiovascular Evaluation (ACE) trial data. Methods: There were 3105 placebo‐treated ACE participants with requisite data for model development. Clinically relevant variables, and those showing nominal univariate association with new‐onset diabetes (P <.10), were entered into BASIC (clinical variables only), EXTENDED (clinical variables plus routinely available laboratory results), and FULL (all candidate variables) logistic regression models. External validation was performed using the Luzhou prospective cohort of 1088 Chinese patients with IGT. Results: Over median 5.0 years, 493 (15.9%) ACE participants developed diabetes. Lower age, higher body mass index, and use of corticosteroids or thiazide diuretics were associated with higher diabetes risk. C‐statistics for the BASIC (using these variables), EXTENDED (adding male sex, fasting plasma glucose, 2‐hour glucose, and HbA1c), and FULL models were 0.610, 0.757, and 0.761 respectively. The EXTENDED model predicted a lower 13.9% 5‐year diabetes risk in the Luzhou cohort than observed (35.2%, 95% confidence interval 31.3%‐39.5%, C‐statistic 0.643). Conclusion: A risk prediction model using routinely available clinical variables can be used to estimate diabetes risk in Chinese people with CHD and IGT. [ABSTRACT FROM AUTHOR]

Using the no-core fiber (NCF)–seven-core fiber (SCF) interference structure, two curvature sensors of Michelson interference type and Mach–Zehnder interference (MZI) type are proposed, respectively. The curvature sensor based on Michelson interference shows wavelength-modulation characteristics, the sensitivity is about −22.76 nm/m−1 with a linearity of 0.9823, the temperature sensitivity is only 0.054 nm/°C, and the effect of temperature on curvature can be negligible. The MZI sensor based on an enlarged taper-embedded cascaded structure is an intensity-modulated sensor. The sensitivities are −63.6271 dB m/m−1 and 93.3293 dBm/m−1 for the forward and reverse curvature, respectively, and the linearities are 0.9987 and 0.9930, respectively. But the strain sensitivity (8.357 × 10−4 dBm/με) of the MZI sensor is so tiny, which can avoid the strain cross effect. The two sensors can be used in the detection of the curvature at different (temperature/strain) conditions. [ABSTRACT FROM AUTHOR]

The development of efficient and stable photocatalysts is of great significance for tailoring energy crisis and environmental pollution. In this study, novelty Sillén-Aurivillius BaBi 4 TiNbO 11 Cl ferroelectric materials were successful synthesized. Results of characterizations exhibit high crystallinity of BaBi 4 TiNbO 11 Cl nanoplates with the less impurity phases were fabricated from NaCl/CsCl molten-salt method due to the sufficient precursor ionic diffusion. This layered crystal structure of BaBi 4 TiNbO 11 Cl nanoplates can promote the separation of photon-generated carriers, and thus its photocatalytic activity is 3.73 and 1.58 times higher than that of other samples, respectively. Since the distortions of [TiO 6 ] and [NbO 6 ] octahedron in [BiTiNbO 7 ] perovskite blocks cause the ferroelectric polarization in BaBi 4 TiNbO 11 Cl, the piezo-photocatalytic performance is also assessed by mechanical force from ultrasound. Further investigations on the piezo-photocatalytic mechanisms of BaBi 4 TiNbO 11 Cl nanoplates, the internal electric fields induced by ferroelectric polarization can promote the efficient separation of free charges effectively, which enhances the catalytic activities of about 4.74 times by the synergistic effect of visible light and ultrasonic excitations. This work focuses on revealing the differences of photocatalytic, piezocatalytic and piezo-photocatalytic mechanisms for BaBi 4 TiNbO 11 Cl nanoplates, which provides a reference to develop other efficient piezo-photocatalysts of Sillén-Aurivillius layered oxyhalide materials. • Novelty Sillén–Aurivillius BaBi 4 TiNbO 11 Cl were synthesized by molten-salt method for the first time. • Piezocatalysis coupled with photocatalysis has been applied to BaBi 4 TiNbO 11 Cl nanoflakes to check their synergistic effect. • Possible electron migration paths for photocatalytic and piezocatalytic mechanisms in BaBi 4 TiNbO 11 Cl nanoplates have been discussed. [ABSTRACT FROM AUTHOR]

Nowadays, cadmium sulfide (CdS) or zinc oxysulfide (Zn(O,S)) are the traditional buffer layer of Cu(In,Ga)Se 2 (CIGS) solar cells. However, these buffer layers contain several disadvantages, such as the complicated synthesis problem and heavy metal toxicity. To solve the above problems, the potential of Bi-based (BiOX: X = Cl, Br) materials employed as buffer layers for efficient CIGS solar cells are investigated by using SCAPS simulation software in this contribution. It can be found that all BiOX materials fabricated from a soft liquid deposition process possess 2D nanosheet structures. A comparison of 2D nanosheet size reveals that BiOBr can form easily compared with BiOCl under the same growth conditions. Simultaneously, DRS and XPS determine the energy band distribution of BiOX materials. Further investigations on the simulated device performance suggest that conversion efficiency of the BiOBr sample is maximum, which is close to that of CdS and much larger than the BiOCl sample, mostly owning to the increased J SC and FF. The reason for this results is that the energy band distribution of BiOBr is similar to that of CdS buffer layer. It also indicates that BiOBr has the potential to serve as a buffer layer material for solar cells. • Conventional cadmium sulfide as a buffer layer for CIGS solar cells has many problems. • BiOX is designed as the novel buffer layer of CIGS solar cell. • The solar cell with BiOBr buffer layer possess the efficiency comparable to that of CdS buffer layer sample. [ABSTRACT FROM AUTHOR]

Developing efficient photocatalyst for the photoreduction of CO2 and degradation of organic pollutants is an effective alternative to address increasingly serious energy problems and environmental pollution. Herein, the isostructural Sillén–Aurivillius oxyhalides, Bi7Fe2Ti2O17X (X = Cl, Br, and I; BFTOX), are fabricated for CO2 reduction and degradation of organic pollutants for the first time. Density functional theory (DFT) calculations show that the valence band maximum (VBM) of BFTOC and BFTOB is contributed by the dispersive 2p orbitals of O-atoms, providing the narrow band gap (Eg) and possibly the stability against self-decomposition deactivation. The photocatalytic activities of BFTOX are strongly affected by the halogens (Cl, Br, and I), namely, the BFTOCl sample displays outstanding activity improvement (3.74 μmol·g−1·h−1) for photocatalytic performance. This is mainly attributed to the high separation of charge carriers, small optical band gap, and extended optical absorption. This work focuses on affording a reference to develop efficient and stable photocatalysts from Sillén-Aurivillius layered oxyhalide materials. [ABSTRACT FROM AUTHOR]

Measuring schematic diagram of the curvature and temperature. [Display omitted] • A novel lateral-offset optic-fiber curvature and temperature sensor is proposed. • Maximum curvature sensitivity can reach −18.75 nm/m−1 with the linearity of 0.9743. • Temperature sensitivity of the sensor is 74 pm/°C with the linearity of 0.9788. • The sensor can be applied in industrial production, building monitoring and so on. Based on the Mach-Zehnder interference principle, a optic-fiber curvature and temperature sensor consisting of a lateral-offset spliced single-mode fiber-four-core fiber-single-mode fiber (SMF-FCF-SMF) interference structure has been proposed and demonstrated. The curvature and temperature characteristics of the sensor with different offset distances are studied in detail. Within the curvature range of 0.042–0.163 m−1, the maximum curvature sensitivity can reach −18.75 nm/m−1. Besides, the temperature sensitivity of the sensor is as high as 74 pm/°C in the range of 30–80 °C. The sensor has good linearity in measuring curvature and temperature with a simple structure, expected to be applied in industrial production, building monitoring, etc. [ABSTRACT FROM AUTHOR]

A novel multi-parameter (refractive index, temperature and curvature) sensor based on the splicing-point tapered FBG-SMF-FCF-SMF (FBG, fiber Bragg grating; SMF, single-mode fiber; FCF, four-core fiber) Mach-Zehnder interferometer (MZI) is proposed and fabricated. Two waist-enlarged tapers formed at the fusion points between SMFs and FCF play the roles of the beam splitter and coupler, respectively. FBG is used to monitor temperature change and to compensate for temperature shift in the measurements of refractive index and curvature. The results show that the extinction ratio of transmission spectrum can reach at 27.22 dB. The sensitivities of the sensor to the external refractive index and curvature are 116.396 nm/RIU and 15.57 pm/m−1, respectively. The temperature sensitivities of MZI and FBG are respectively 67.31 pm/℃ and 8.73 pm/℃ in the range of 0-80℃. All the three-parameter measurements present good linear relationship. The sensor has the advantages of simple structure, easy process and low cost, which can be used in multi-parameter detection. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with cardiovascular disease are at high risk of type 2 diabetes (T2D), but little has been done to provide robust T2D risk estimates. We used Acarbose Cardiovascular Evaluation (ACE) trial data to develop a T2D risk calculator for Chinese people with coronary heart disease (CHD) and impaired glucose tolerance (IGT). Methods: ACE recruited 6522 Chinese CHD patients with IGT, randomized 1:1 to acarbose or placebo, with prospective ascertainment of new-onset diabetes over median 5.0 years. Logistic regression was used to develop basic and full risk prediction models in the 6238 with the requisite baseline data. Clinically relevant variables and variables showing a univariate association (P<0.1) with incident diabetes were included. Results: Overall 918 (15%) of 6238 participants developed diabetes. The basic model, using only clinical variables, was a poor fit with an area under the receiver-operating characteristic curve (AUC) of 0.60, whilst the full model including routinely-available laboratory results had an AUC of 0.76 with excellent goodness of fit (Table). Conclusion: In Chinese people with IGT and CHD, lower age, male sex, obesity, prior hypertension, calcium channel blocker use, nondiabetic hyperglycaemia and dyslipidaemia were major determinants for new-onset diabetes. A model comprising these factors can be used to predict 5-year T2D risk. Disclosure: S. Xu: None. C.A. Scott: None. R.L. Coleman: None. J. Tuomilehto: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; AstraZeneca. Research Support; Self; Bayer AG. R.R. Holman: Advisory Panel; Self; Bayer AG, Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. Other Relationship; Self; AstraZeneca, Bayer AG, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc. [ABSTRACT FROM AUTHOR]

Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine–topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change −7·98, 95% CI −9·27 to −6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD −5·79, 95% CI −6·34 to −5·25). Naltrexone–bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine–topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD −11·40, 95% CI −12·51 to −10·29). In adults with overweight and obesity, phentermine–topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University. [ABSTRACT FROM AUTHOR]

Background: Adverse childhood experiences (ACEs), including childhood maltreatment, have been linked with increased risk of diabetes and obesity during adulthood. A comprehensive assessment on the associations between childhood maltreatment and all major endocrine diseases, as well as the relative importance of different proposed mechanistic pathways on these associations, is currently lacking. Methods: Based on the UK Biobank, we constructed a cohort including 151,659 participants with self-reported data on childhood maltreatment who were 30 years of age or older on/after January 1, 1985. All participants were followed from the index date (i.e., January 1, 1985, or their 30th birthday, whichever came later) until the first diagnosis of any or specific (12 individual diagnoses and 9 subtypes) endocrine diseases, death, or the end of follow-up (December 31, 2019), whichever occurred first. We used Cox models to examine the association of childhood maltreatment, treated as continuous (i.e., the cumulative number of experienced childhood maltreatment), ordinal (i.e., 0, 1 and ≥ 2), or binary (< 2 and ≥ 2) variable, with any and specific endocrine diseases, adjusted for multiple covariates. We further examined the risk of having multiple endocrine diseases using Linear or Logistic Regression models. Then, sequential mediation analyses were performed to assess the contribution of four possible mechanisms (i.e., suboptimal socioeconomic status (SES), psychological adversities, unfavorable lifestyle, and biological alterations) on the observed associations. Results: During an average follow-up of 30.8 years, 20,885 participants received a diagnosis of endocrine diseases. We observed an association between the cumulative number of experienced childhood maltreatment and increased risk of being diagnosed with any endocrine disease (adjusted hazard ratio (HR) = 1.10, 95% confidence interval 1.09–1.12). The HR was 1.26 (1.22–1.30) when comparing individuals ≥ 2 with those with < 2 experienced childhood maltreatment. We further noted the most pronounced associations for type 2 diabetes (1.40 (1.33–1.48)) and hypothalamic–pituitary–adrenal (HPA)-axis-related endocrine diseases (1.38 (1.17–1.62)), and the association was stronger for having multiple endocrine diseases, compared to having one (odds ratio (95% CI) = 1.24 (1.19–1.30), 1.35 (1.27–1.44), and 1.52 (1.52–1.53) for 1, 2, and ≥ 3, respectively). Sequential mediation analyses showed that the association between childhood maltreatment and endocrine diseases was consistently and most distinctly mediated by psychological adversities (15.38 ~ 44.97%), while unfavorable lifestyle (10.86 ~ 25.32%) was additionally noted for type 2 diabetes whereas suboptimal SES (14.42 ~ 39.33%) for HPA-axis-related endocrine diseases. Conclusions: Our study demonstrates that adverse psychological sequel of childhood maltreatment constitutes the main pathway to multiple endocrine diseases, particularly type 2 diabetes and HPA-axis-related endocrine diseases. Therefore, increased access to evidence-based mental health services may also be pivotal in reducing the risk of endocrine diseases among childhood maltreatment-exposed individuals. [ABSTRACT FROM AUTHOR]

• Sustainable layered heterojunction Z-Scheme CN/Bi 4 NbO 8 X (Cl, Br) photocatalyst. • Successful fabrication of layered heterojunction Z-Scheme CN/Bi 4 NbO 8 X (Cl, Br) by hydrothermal approach. • Efficient for the decomposition of RhB and Trypan Blue dye in less time. • Improved visible light photocatalytic activity of the synthesized compound. A highly potential visible light active g-C 3 N 4 /Bi 4 NbO 8 X (Cl, Br) heterojunction photocatalysts were constructed at the interface of the coupling between Bi 4 NbO 8 X (Cl, Br) and g-C 3 N 4. The band gap value of heterojunctions g-C 3 N 4 /Bi 4 NbO 8 Br-20% (CNBNB-3), g-C 3 N 4 /Bi 4 NbO 8 Cl-20% (CNBNC-3), and pristine materials g-C 3 N 4 (CN), Bi 4 NbO 8 Cl and Bi 4 NbO 8 Br were analyzed to be 2.68 eV, 2.69 eV and 2.74 eV, 2.46 eV and 2.48 eV, respectively. The degradation performance of optimized CNBNC-3 and CNBNB-3 photocatalysts revealed much superior removal efficiency of 97% and 84% than the pristine material for rhodamine B. The synthesized photocatalysts maintained good recyclable stability after five consecutive cycles and potentially capable of pollutant degradation. The electrochemical impedance and photoluminescence spectroscopy revealed that the migration and separation efficiency of photogenerated charge carriers of photocatalyst were boosted, while reduced recombination rate was observed. The photocatalytic reaction mechanism also revealed the superoxide ·O 2 − and •OH radicals are the main active species responsible for the pollutant degradation. [ABSTRACT FROM AUTHOR]

Background: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs.Methods: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678.Findings: 14 605 citations were identified by our search, of which 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·41, 95% CI -12·54 to -10·27).Interpretation: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective.Funding: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University. [ABSTRACT FROM AUTHOR]

Objective: We examined the impact of acarbose, an α-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation (ACE) trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD).Research Design and Methods: Participants were randomly assigned to acarbose or placebo and followed with four monthly fasting plasma glucose (FPG) tests and annual oral glucose tolerance tests. Incident diabetes was defined as two successive diagnostic FPG levels ≥7 mmol/L or 2-h plasma glucose (PG) levels ≥11.1 mmol/L while taking study medication or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG <6.1 mmol/L and 2-h PG <7.8 mmol/L. Intention-to-treat and on-treatment analyses were conducted using Poisson regression models, overall and for subgroups (age, sex, CHD type, HbA1c, FPG, 2-h PG, BMI, estimated glomerular filtration rate, for IGT alone, for IGT + impaired fasting glucose, and for use of thiazides, ACE inhibitors [ACEis]/angiotensin receptor blockers [ARBs], β-blockers, calcium channel blockers, or statins).Results: Incident diabetes was less frequent with acarbose compared with placebo (3.2 and 3.8 per 100 person-years, respectively; rate ratio 0.82 [95% CI 0.71, 0.94], P = 0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose compared with placebo (16.3 and 14.1 per 100 person-years, respectively; 1.16 [1.08, 1.25], P < 0.0001). This effect was greater in participants not taking an ACEi or ARB (1.36 [1.21, 1.53], Pinteraction = 0.0006). The likelihood of remaining in normoglycemic regression did not differ between the acarbose and placebo groups (P = 0.41).Conclusions: Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic cardiomyopathy is a cardiac dysfunction in patients with diabetes which may lead to overt heart failure and death. Toll-like receptor (TLR) signaling triggers diabetic cardiomyopathy through various mechanisms, one of which is the upregulation of TLR4 expression. The aim of this study was to delineate the role of TLR4 in diabetic cardiomyopathy. Methods: C57BL/6 mice were injected with streptozotocin to induce diabetes. The experimental and control groups were treated with 5 μg of TLR4 small interfering RNA (siRNA) or scrambled siRNA. Cardiac histopathology was evaluated by hematoxylin and eosin, Sirius red, and immunofluorescence staining after treatment with TLR4 siRNA. The myocardial fibrosis and inflammatory factors were detected by quantitative real-time polymerase chain reaction after treatment with TLR4 siRNA. The myocardial function was evaluated by echocardiography after treatment with TLR4 siRNA. Results: Compared with non-diabetic mouse hearts, hypertrophy, fibrosis, inflammation of cardiomyocytes, and myocardial dysfunction were significantly increased in diabetic mice (p < 0.05). Knockdown of TLR4 decreased hypertrophy, fibrosis, inflammation of cardiomyocytes, and myocardial dysfunction (p < 0.05). Cardiomyocytic cross-sectional areas in hearts of TLR4 siRNA-treated diabetic mice were similar to those of the sham-treated mice (p > 0.05). The induction of expression of cardiac fetal genes, beta-myosin heavy chain (β-MHC) and atrial natriuretic peptide (ANP), which are two markers of cardiac hypertrophy, was significantly reduced in TLR4 siRNA-treated hearts compared with controls (p < 0.05). Moreover, siRNA-mediated silencing of TLR4 reduced diabetes-induced collagen deposition (p < 0.05). Paralleled with changes in collagen deposition and the expression of collagen I and collagen III, knockdown of TLR4 also reduced the expression of transforming growth factor-β1 (TGFβ1) mRNA (p < 0.05). The increased expression of intercellular cell adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was significantly attenuated by TLR4 siRNA treatment in the hearts of diabetic mice (p < 0.05). Furthermore, both fractional shortening (FS) and ejection fraction (EF) values were preserved in TLR4 siRNA-treated diabetic mice compared with control siRNA-treated mice (31.80% ± 2.82% vs. 28.50% ± 5.83% for FS, p < 0.05) (57.95% ± 6.48% vs. 45.34% ± 4.25% for EF, p < 0.05). Conclusion: Our study used siRNA to specifically silence TLR4 gene expression in the diabetic mouse heart in vivo and to investigate the role that TLR4 plays in diabetic cardiomyopathy. It is likely that silencing of the TLR4 gene through siRNA could prevent the development of diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]