Prevalence of the virulence genes and their correlation with carbapenem resistance amongst the Pseudomonas aeruginosa strains isolated from a tertiary hospital in China.

Pseudomonas aeruginosa is one of the top-listed pathogens in nosocomial infection. It is notorious for its complicated virulence system and rapid adaptability to drugs or antimicrobials. In this study, we aimed to evaluate the prevalence of sixteen virulence genes in four groups including type III secretion system, biofilm formation, extracellular toxin biosynthesis and enzymes amongst 209 clinical Pseudomonas aeruginosa strains. We investigated the different distribution patterns of virulence genotypes based on carbapenem-resistant phenotype or the carriage of carbapenemase genes. The detection rate of each virulence gene varied greatly. phzM and plcN were detected in all collected strains, while pilB and exoU were only carried by a small portion of isolates (6.7% and 16.3%). Additionally, the number of genotypes observed in each group of examined virulence genes ranged from 4 to 8. Only the distribution of genotypes of type III secretion system showed statistical difference between carbapenem-mediated or carbapenem-resistant and carbapenem-sensitive strains. The virulence genotype of Pseudomonas aeruginosa was possibly interrelated to its resistance mechanism. Further research suggested that one particular TTSS genotype exhibited higher ratio in carbapenemase-producing strains and exoS was less frequently detected in CRPA strains carrying carbapenemase gene. Generally, the significant genetic diversity of virulence genes amongst Pseudomonas aeruginosa strains was highlighted in this study. Specific TTSS genotypes were associated with carbapenem-resistance. In particular, certain incompatibility might exist between exoS and carbapenemase genes, which provided valuable information for further understanding the relationship between carbapenem resistance and virulence.

Cross-reactive antibodies against monkeypox virus exist in the population immunized with vaccinia Tian Tan strain in China.

Monkeypox virus (MPXV) belongs to the Orthopoxvirus genus. The worldwide outbreak of MPXV in 2022 has caused widespread concerns. Cross-reactive antibodies induced by vaccinia-inoculation can provide protection against reinfection by MPXV. The vaccinia Tian Tan (VTT) strain, which was widely inoculated in the Chinese population before the 1980s, has genomic differences from other vaccinia strains, although they all belong to the orthopoxviruses family. The current seroprevalence of VTT-vaccinated populations remains unclear more than four decades after the termination of vaccination campaigns in China. Our results showed that cross-reactive IgG antibodies against MPXV were present in 31.8% (75/236) of vaccinees four decades after VTT-vaccination, suggesting that vaccination with VTT may provide long-term protection against MPXV infection in some individuals.

Two-dimensional measurements of receptor-ligand interactions.

Gaining insight into the two-dimensional receptor-ligand interactions, which play a significant role in various pivotal biological processes such as immune response and cancer metastasis, will deepen our understanding of numerous physiological and pathological mechanisms and contribute to biomedical applications and drug design. A central issue involved is how to measure the in situ receptor-ligand binding kinetics. Here, we review several representative mechanical-based and fluorescence-based methods, and briefly discuss the strengths and weaknesses for each method. In addition, we emphasize the great importance of the combination of experimental and computational methods in studying the receptor-ligand interactions, and further studies should focus on the synergistic development of experimental and computational methods.

Insight into adsorption process and mechanisms of Cr(III) using carboxymethyl cellulose-g-poly(acrylic acid-co-acrylamide)/attapulgite composite hydrogel.

Cr(III) as one of the most concerned potentially toxic elements, is discharged from relevant industries and Cr(VI) reduction. Hydrogel-based adsorption could be one of the promising approaches for Cr(III) removal. Featured with environmental friendliness and low cost, carboxymethyl cellulose (CMC) was employed for the hydrogel synthesis, and attapulgite (APT) could be used to strengthen its stability. However, the adsorption performance and mechanisms need to be examined. In the present study, carboxymethyl cellulose-g-poly(acrylic acid-co-acrylamide)/ attapulgite (CMC-g-p(AA-co-AM)/APT) was synthesised via in situ copolymerisation. Its efficacy for removing Cr(III) from an aqueous solution was investigated using batch adsorption experiments. Results showed that the introduction of APT enhanced the thermal stability but decreased the swelling performance of the hydrogel. The prepared hydrogel could strongly adsorb Cr(III) at a wide pH range of 3.0-7.0. Cr(III) can be efficiently removed by the composite hydrogel within 1-2 h. At low concentration, CMC-g-p(AA-co-AM)/APT could slightly adsorbed more Cr(III) than CMC-g-p(AA-co-AM). The maximum absorption of CMC-g-p(AA-co-AM) and CMC-g-p(AA-co-AM)/APT were 74.8 and 47.7 mg/g at 298 K, respectively. The negative value of ΔHo and ΔGo indicated the adsorption of Cr(III) onto the two studied hydrogels is an exothermic and spontaneous process. Ion exchange and complexation, as implied by EDS, FT-IR and XPS, combining with electrostatic attraction are the possible adsorption mechanisms for Cr(III) onto the prepared hydrogels. All the results above suggests that the composite hydrogel CMC-g-p(AA-co-AM)/APT can be a promising candidate for the removal of Cr(III) from waste water.

Biochemical, histopathological and untargeted metabolomic analyses reveal hepatotoxic mechanism of acetamiprid to Xenopus laevis.

Acetamiprid, a commonly detected neonicotinoid in aquatic ecosystems, poses a threat to aquatic non-target organisms. However, limited information is available on the toxic effects of acetamiprid on nontarget aquatic organisms. This study assessed the toxic effects of acetamiprid on Xenopus laevis, a typical model organism. The acute toxicity for 96 h revealed that acetamiprid had detrimental effects with a median lethal concentration (LC50) value of 64.48 mg/L. Toxicity assays, including oxidative stress, histopathology and untargeted metabolomics of acetamiprid to X. laevis, were performed for 28 d at 1/10 and 1/100 LC50 by studying the liver, which is the most antioxidant and major metabolic organ. The results demonstrated that acetamiprid exposure significantly changed the oxidant status of and caused histological damage to the liver. Furthermore, the untargeted metabolomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified the endogenous metabolites that were significantly altered. There were 89 differential metabolites compared to the controls: 64 in the 1/10 LC50 group, 47 in the 1/100 LC50 group, and 23 metabolites in the 1/10 LC50 group were the same as those in the 1/100 LC50 group. Sixteen pathways that were mainly associated with amino acid metabolism and lipid metabolism, such as sphingolipid metabolism, glycerophospholipid metabolism and histidine metabolism, were disrupted, revealing the hepatotoxic effects of acetamiprid on X. laevis at the molecular level. These findings provide crucial information for evaluating the aquatic risks of neonicotinoids.

Prevalence and risk factors of metabolic syndrome among adults in Hainan Province / 中国热带医学

@#Abstract: Objective　This study aims to explore the prevalence and risk factors of metabolic syndrome (MS) among the adults in Hainan Province, and to provide scientific basis for MS prevention and control. Methods　A multi-stage cluster random sampling method was applied to select 3 690 permanent residents aged 18 years and above in Hainan Province. The survey was conducted by trained investigators using household appointments and centralized surveys. A questionnaire survey, physical measurement, and laboratory examination were conducted after the collection of blood samples. The processed samples were then tested by a quality-controlled laboratory. Finally, we analysed the prevalence of metabolic syndrome (MS) and its relationship with population characteristics and health-related behaviors. Results　The crude prevalence of MS in the population aged 18 and above in Hainan province was 19.46% and the standardized prevalence was 13.21%, with a higher rate in urban areas (22.21%) than in rural areas (18.13%). The prevalence of MS increased with age (P<0.001), and there were significant differences in MS prevalence among different marital and occupational statuses (P<0.01). Logistic regression results indicated that the age groups of 40-<50 years (OR=2.986, 95%CI:1.355-6.580), 50-<60 years (OR=3.739, 95%CI: 1.715-8.151), 60-<70 years (OR=3.890, 95%CI: 1.769-8.556), 70 years and above (OR=3.927, 95%CI: 1.758-8.771), technical, transportation and production personnel (OR=1.579, 95%CI: 1.033-2.412), retired (OR=1.788, 95%CI: 1.415-2.259), unemployed (OR=1.503, 95%CI: 1.044-2.165), smoking cessation (OR=1.582, 95%CI: 1.162-2.154), insufficient intake of fruits and vegetables (OR=1.196, 95%CI: 1.005-1.422), and insufficient physical activity (OR=1.437, 95%CI: 1.155-1.787) were all associated with the prevalence of MS. Among the investigated subjects, 30.22% of them had one abnormal component, with hyperglycemia being the highest (54.44%); 24.25% of them had two abnormal components, with "hyperglycemia + hypertension" being the highest (33.30%); and 19.46% had three or more components, with "overweight/obesity + hyperglycemia + hypertension" being the highest (24.79%). Conclusions　The prevalence of MS in Hainan Province is on the rise, and effective lifestyle intervention measures are needed to reduce the risk of MS.

Under-reporting of mortality surveillance in Hainan, 2018-2020 / 中国热带医学

@#Objective　To understand the overall under-reporting of cause of death monitoring in Hainan Province, and to provide a scientific basis for evaluating the data from death registration report and health planning in Hainan. Methods　Multi-stage cluster random sampling was used, all towns/streets in cities and counties of the province were ranked from highest to lowest in terms of crude death rate, divided into high, medium and low levels (the number of each level was basically the same), and one was randomly selected from each level. A total of three towns/streets were used as survey areas, and all households in the area were survey households. Death information of resident population during 2018-2020 was collected and compared with routine surveillance data for the same period. The under-reporting rate was calculated, and comparison between groups was performed by chi-square. Results　A total of 12 583 death cases were investigated from 2018 to 2020, and the average mortality was 621.48/105. 4 809 cases were missed with the total under-reporting rate of 38.22%. The under-reporting rate from 2018 to 2020 were 39.75%, 39.99% and 34.77% (χ2=30.404, P<0.01) respectively. The under-reporting rate in eastern and central and western areas were 30.33%, 30.10% and 60.15% (χ2=931.901, P<0.01) respectively. The negative rate were different in different years old group (χ2=14.834, P<0.05). Of the 4 809 under-reported cases, as many as 93.49% died at home, and the composition of deaths in hospitals was about 10 times higher in the center than in the east and west, and the proportion of those who died in hospital in central areas was about 10 times higher than in eastern and central areas. Conclusions　More than half of the cities and counties in Hainan Province have improved the completeness of cause of death surveillance data. The under-reporting rate in age group <5 years are still high, and regular under-reporting investigations are still needed to strengthen the reporting and management of death information.

High-Performance Lithium-Ion Storage of FeTiO3 with Morphology Adjustment and Niobium Doping.

Ferrous titanate (FeTiO3) has a high theoretical capacity and physical and chemical properties stability, so it is a potential lithium anode material. In this study, FeTiO3 nanopowder and nanosheets were prepared by the sol-gel method and the hydrothermal method. In addition, niobium-ion doping was carried out, the radius of Nb close to Ti so the Nb can easily enter into the FeTiO3 lattice. Nb can provide more free electrons to improve the electrochemical performance. Then, the effects of the morphology and niobium doping on the microstructure and electrochemical properties of FeTiO3 were systematically studied. The results show that FeTiO3 nanosheets have a better lithium storage performance than nanopowders because of its high specific surface area. A certain amount of niobium doping can improve the electrochemical performance of FeTiO3. Finally, a 1 mol% niobium-doping FeTiO3 nanosheets (1Nb-FTO-S) electrode provided a higher specific capacity of 782.1 mAh g-1 at 50 mA g-1. After 200 cycles, the specific capacity of the 1Nb-FTO-S electrode remained at 509.6 mAh g-1. It is revealed that an increased specific surface area and ion doping are effective means to change the performance of lithium, and the proposed method looks promising for the design of other inorganic oxide electrode materials.

Evaluation of a multiplex PCR kit for detection of 17 respiratory pathogens in hospitalized patients.

Background: Rapid pathogen identification is critical for optimizing diagnosis and treatment of infectious diseases. Multiplex polymerase chain reaction (PCR) is a sensitive, broad-spectrum molecular detection technique that is simple and rapid to perform. It is capable of simultaneously screening for multiple pathogens within a short time range. Here, we designed and evaluated a multiplex PCR kit for the identification of 17 common respiratory pathogens in clinical samples from hospitalized patients. Methods: A total of 452 samples from hospitalized patients, including 242 respiratory and 210 non-respiratory samples, were analyzed for 13 bacteria and 4 fungi by a multiplex fluorescent PCR kit. The diagnostic performance of the kit was assessed by considering routine microbiology as the reference standard. Results: The overall positivity rate of the multiplex PCR kit was 86.9%, much higher than that noted on routine microbiology (56.9%). Furthermore, the co-infection detection rate was also significantly higher than that noted on routine microbiology (69.5% vs. 15.0%). Compared with routine microbiology, kit sensitivity was >90% for detection of most target bacteria, with a negative predictive value (NPV) of >99%, especially for detection of Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Stenotrophomonas maltophilia, Enterococcus faecium, Enterococcus faecalis and Escherichia coli. The kit was noted to be particularly superior in identifying Stenotrophomonas maltophilia and Streptococcus pneumoniae as compared to routine microbiology. The multiplex PCR kit was noted to be less sensitive (33.3-59.6%) and more specific (93.9-100.0%) for detection of mycobacteria and fungi. Conclusions: Our multiplex PCR kit offers a rapid and sensitive diagnosis of common bacterial pneumonia, although sensitivity for mycobacteria and fungi warrants enhancement. Further optimization includes minimizing false positivity and increasing relevance to clinical application.

Erythromycin Estolate Is a Potent Inhibitor Against HCoV-OC43 by Directly Inactivating the Virus Particle.

In addition to antibacterial effects, macrolide antibiotics exhibit other extensive pharmacological effects, such as anti-inflammatory and antiviral activities. Erythromycin estolate, one of the macrolide antibiotics, was previously investigated to effectively inhibit infections of various flaviviruses including Zika virus, dengue virus, and yellow fever virus, but its antiviral effect against human coronavirus remains unknown. Thus, the current study was designed to evaluate the antiviral efficacy of erythromycin estolate against human coronavirus strain OC43 (HCoV-OC43) and to illustrate the underlying mechanisms. Erythromycin estolate effectively inhibited HCoV-OC43 infection in different cell types and significantly reduced virus titers at safe concentration without cell cytotoxicity. Furthermore, erythromycin estolate was identified to inhibit HCoV-OC43 infection at the early stage and to irreversibly inactivate virus by disrupting the integrity of the viral membrane whose lipid component might be the target of action. Together, it was demonstrated that erythromycin estolate could be a potential therapeutic drug for HCoV-OC43 infection.

Insights into intercellular receptor-ligand binding kinetics in cell communication.

Cell-cell communication is crucial for cells to sense, respond and adapt to environmental cues and stimuli. The intercellular communication process, which involves multiple length scales, is mediated by the specific binding of membrane-anchored receptors and ligands. Gaining insight into two-dimensional receptor-ligand binding kinetics is of great significance for understanding numerous physiological and pathological processes, and stimulating new strategies in drug design and discovery. To this end, extensive studies have been performed to illuminate the underlying mechanisms that control intercellular receptor-ligand binding kinetics via experiment, theoretical analysis and numerical simulation. It has been well established that the cellular microenvironment where the receptor-ligand interaction occurs plays a vital role. In this review, we focus on the advances regarding the regulatory effects of three factors including 1) protein-membrane interaction, 2) biomechanical force, and 3) bioelectric microenvironment to summarize the relevant experimental observations, underlying mechanisms, as well as their biomedical significances and applications. Meanwhile, we introduce modeling methods together with experiment technologies developed for dealing with issues at different scales. We also outline future directions to advance the field and highlight that building up systematic understandings for the coupling effects of these regulatory factors can greatly help pharmaceutical development.

The Effect of Non-Cognitive Ability on Farmer's Ecological Protection of Farmland: Evidence from Major Tea Producing Areas in China.

Ecological protection of farmland is an important means to reduce agricultural non-point source pollution and improve the quality of agricultural products. As the main body of current agricultural production and operation, the aging labor force has insufficient cognitive ability and low ability to learn actively, which is not conducive to transforming the green output. However, non-cognitive abilities closely related to the acquired environment can promote the elderly farmers' farmland ecological protection behavior by improving life satisfaction and social adaptability. Based on the above background, using the survey data of 964 farmers in China, the bivariate Probit model was used to empirically test the influence mechanism of non-cognitive ability on the ecological protection behavior of farmland. The study found that non-cognitive ability significantly promoted farmer's ecological protection of farmland in China. Specifically, the variables of non-cognitive ability, social communication ability, active learning ability, self-efficacy, stress resistance, altruistic tendency and individual resilience were found to significantly promote ecological protection of farmland. Mechanism analysis showed that non-cognitive ability promoted the ecological protection behavior of farmland by expanding social capital, information channels and improving technical value perception. A heterogeneity analysis revealed that non-cognitive ability had a greater impact on ecological protection behavior of farmland in the elderly and low-income groups. Therefore, government should attach importance to improving farmers' non-cognitive abilities, further increase technical publicity, and build a communication platform for farmers in order to promote the ecological protection of farmland.

Interaction Mechanisms and Application of Ozone Micro/Nanobubbles and Nanoparticles: A Review and Perspective.

Ozone micro/nanobubbles with catalytic processes are widely used in the treatment of refractory organic wastewater. Micro/nanobubble technology overcomes the limitations of ozone mass transfer and ozone utilization in the application of ozone oxidation, and effectively improves the oxidation efficiency of ozone. The presence of micro/nanobubbles keeps the catalyst particles in a dynamic discrete state, which effectively increases the contact frequency between the catalyst and refractory organic matter and greatly improves the mineralization efficiency of refractory organic matter. This paper expounds on the characteristics and advantages of micro/nanobubble technology and summarizes the synergistic mechanism of microbubble nanoparticles and the mechanism of catalyst ozone micro/nanobubble systems in the treatment of refractory organics. An interaction mechanism of nanoparticles and ozone microbubbles is suggested, and the proposed theories on ozone microbubble systems are discussed with suggestions for future studies on systems of nanoparticles and ozone microbubbles.

Prediction of Red Blood Cell Demand for Pediatric Patients Using a Time-Series Model: A Single-Center Study in China.

Background: Red blood cells (RBCs) are an essential factor to consider for modern medicine, but planning the future collection of RBCs and supply efforts for coping with fluctuating demands is still a major challenge. Objectives: This study aimed to explore the feasibility of the time-series model in predicting the clinical demand of RBCs for pediatric patients each month. Methods: Our study collected clinical RBC transfusion data from years 2014 to 2019 in the National Center for Children's Health (Beijing) in China, with the goal of constructing a time-series, autoregressive integrated moving average (ARIMA) model by fitting the monthly usage of RBCs from 2014 to 2018. Furthermore, the optimal model was used to forecast the monthly usage of RBCs in 2019, and we subsequently compared the data with actual values to verify the validity of the model. Results: The seasonal multiplicative model SARIMA (0, 1, 1) (1, 1, 0)12 (normalized BIC = 8.740, R 2 = 0.730) was the best prediction model and could better fit and predict the monthly usage of RBCs for pediatric patients in this medical center in 2019. The model residual sequence was white noise (Ljung-Box Q(18) = 15.127, P > 0.05), and its autocorrelation function (ACF) and partial autocorrelation function (PACF) coefficients also fell within the 95% confidence intervals (CIs). The parameter test results were statistically significant (P < 0.05). 91.67% of the actual values were within the 95% CIs of the forecasted values of the model, and the average relative error of the forecasted and actual values was 6.44%, within 10%. Conclusions: The SARIMA model can simulate the changing trend in monthly usage of RBCs of pediatric patients in a time-series aspect, which represents a short-term prediction model with high accuracy. The continuously revised SARIMA model may better serve the clinical environments and aid with planning for RBC demand. A clinical study including more data on blood use should be conducted in the future to confirm these results.

Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator.

Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose- and time- dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection.

Role and Mechanism of lncRNA-pvt1 in the Pathogenesis of Acute Lymphoblastic Leukemia in Children.

Objective: To investigate the role and mechanism of lncRNA-pvt1 in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). Methods: The expression of lncRNA-pvt1 in bone marrow tissues of ALL patients after initial diagnosis and complete remission was detected by RT-PCR to explore its possible involvement in the pathogenesis of ALL. The proliferation and apoptosis of Jurkat cells transfected with lncRNA-pvt1 were observed by MTT and flow cytometry. Results: lncRNA-pvt1 expression was upregulated in bone marrow of ALL patients. Knockdown of lncRNA-pvt1 inhibited Jurkat cell proliferation and increased its apoptosis rate. Conclusion: Silencing lncRNA-pvt1 expression can inhibit the development of ALL.

Measuring Laplace pressure and imaging the actin cortex during cytokinesis in cultured cells.

Laplace pressure is an important regulator of cell dynamics and behavior during cytokinesis. Here, we provide a protocol to measure Laplace pressure in cultured cells using a micropipette and describe the steps for imaging the actin cortex during cytokinesis. The quantification steps allow tracing dynamic change in Laplace pressure and displaying dynamic response of the actin cortex during cytokinesis in HeLa cells. This protocol can be applied to any cultured cell type during various stages of cell division. For complete details on the use and execution of this protocol, please refer to Wang et al. (2021).

Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation.

OBJECTIVE: Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A2a receptor (A2aR) in rats with myocardial ischemia-reperfusion (MI/R). METHODS: Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the A2R agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + A2aR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A2aR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. RESULTS: Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A2aR and collagen I and collagen III was found (p = 0.00). CONCLUSION: SFI activated the A2aR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.

Adiposity and risks of vascular and non-vascular mortality among Chinese adults with type 2 diabetes: a 10-year prospective study.

INTRODUCTION: Among individuals with diabetes, high adiposity has been associated with lower cardiovascular disease (CVD) mortality (the so-called 'obesity paradox' phenomenon) in Western populations, for reasons that are still not fully elucidated. Moreover, little is known about such phenomena in Chinese adults with diabetes among whom very few were obese. We aimed to assess the associations of adiposity with vascular and non-vascular mortality among individuals with diabetes, and compare these with associations among individuals without diabetes. RESEARCH DESIGN AND METHODS: In 2004-2008, the prospective China Kadoorie Biobank recruited >512 000 adults from 10 areas in China. After ~10 years of follow-up, 3509 deaths (1431 from CVD) were recorded among 23 842 individuals with diabetes but without prior major diseases at baseline. Cox regression yielded adjusted HRs associating adiposity with mortality. RESULTS: Among people with diabetes, body mass index (BMI) (mean 25.0 kg/m2) was positively log linearly associated with CVD incidence (n=9943; HR=1.19 (95% CI 1.15 to 1.22) per 5 kg/m2), but showed U-shaped associations with CVD and overall mortality, with lowest risk at 22.5-24.9 kg/m2. At lower BMI, risk of death (n=671) within 28 days of CVD onset was particularly elevated, with an HR of 3.26 (95% CI 2.29 to 4.65) at <18.5 kg/m2 relative to 22.5-24.9 kg/m2, but no higher mortality risk at BMI ≥25.0 kg/m2. These associations were similar in self-reported and screen-detected diabetes, and persisted after extensive attempts to address reverse causality and confounding. Among individuals without diabetes (mean BMI 23.6 kg/m2; n=23 305 deaths), there were less extreme excess mortality risks at low BMI. CONCLUSIONS: Among relatively lean Chinese adults with diabetes, there were contrasting associations of adiposity with CVD incidence and with mortality. The high mortality risk at low and high BMI levels highlights, if causal, the importance of maintaining normal weight among people with diabetes.

Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report.

BACKGROUND: Gaucher disease (GD) is caused by a GBA1 gene mutation that leads to decreased acid ß-glucosidase activity [glucocerebrosidase (GCase)]. This study aimed to identify and characterise compound heterozygous mutations in GBA1 in a patient with type 1 GD. CASE SUMMARY: Here, we report a rare adult-onset type 1 GD in a 46-year-old female patient with clinical manifestations of giant spleen, thrombocytopenia, and bone pain, diagnosed by enzymatic and genetic testing. Enzymology and whole exome sequencing revealed heterozygous missense mutations in exon 10 c.1448T>C (p.L483P) and exon 7 c.928A>G (p.S310G) of GBA1. The latter was first reported in patients with GD. Structural modelling showed that p.S310G and p.L483P were distant from the GCase active site. The p.S310G mutation in domain 1 may decrease stability between the α2 and α3 helices of GBA1. The p.L483P mutation in domain 2 reduced the van der Waals force of the side chain and disrupted the C-terminal ß-sheet. The patient was treated with imiglucerase replacement therapy, and her condition was stable. CONCLUSION: The p.L483P/p.S310G novel compound heterozygous mutation underlies type 1 GD and likely affects GCase protein function. This is the first description of p.S310G being associated with mild type 1 GD in the context of a coinherited p.L483P mutation.