The efficacy of low/lactose-free milk powder in the treatment of lactose intolerance in infants: A protocol for systematic review and meta analysis.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of formula milk powder in the treatment of lactose intolerance in children, and to provide an evidence-based medicine basis for the rational use of drugs in children with lactose intolerance caused by various reasons by meta-analysis. METHODS: Use computers to search major databases, including Web of Science, PubMed, CNKI, Wanfang Data Knowledge Service Platform, and other databases, the retrieval time is from the establishment of the database to April 2023. The collected literatures were screened, data extracted and processed, and then meta-analysis was performed by Review-Manager 5.4 statistical software. RESULTS: A total of 10 randomized controlled trials were included, with 1112 patients, including 562 patients in the treatment group and 550 patients in the control group. The control group was treated with conventional therapy, and the treatment group was treated with lactose-free/low-lactose milk powder on the basis of conventional therapy. The results of the meta-analysis showed that the clinical efficacy of the treatment group was significantly better than that of the control group [odds ratio=6.01, 95% confidence interval (CI): 3.94-9.18, P<0.00001], the course of disease in the treatment group was shorter than that in the control group (mean difference=-1.45, 95% CI: -1.76 to -1.13, P<0.0001). The antidiarrhea time of the treatment group was shorter than that of the control group, and the difference between the 2 groups was statistically significant (mean difference=-1.41, 95% CI: -1.67 to -1.15, P<0.0001). CONCLUSION: Low/lactose-free milk powder can improve clinical efficacy and shorten the course of treatment in infants with lactose intolerance, which can be demonstrated by further large-scale clinical studies.

A sensor platform based on SERS detection/janus textile for sweat glucose and lactate analysis toward portable monitoring of wellness status.

Herein we report a wearable sweat sensor of a Janus fabric based on surface enhanced Raman scattering (SERS) technology, mainly detecting the two important metabolites glucose and lactate. Janus fabric is composed of electrospinning PU on a piece of medical gauze (cotton), working as the unidirectional moisture transport component (R = 1305%) to collect and transfer sweat efficiently. SERS tags with different structures act as the probe to recognize and detect the glucose and lactate in high sensitivity. Core-shell structured gold nanorods with DTNB inside (AuNRs@DTNB@Au) are used to detect lactate, while gold nanorods with MPBA (AuNRs@MPBA) are used to detect glucose. Through the characteristic SERS information, two calibration functions were established for the concentration determination of glucose and lactate. The concentrations of glucose and lactate in sweat of a 23 years volunteer during three-stage interval running are tested to be 95.5, 53.2, 30.5 µM and 4.9, 13.9, 10.8 mM, indicating the glucose (energy) consumption during exercise and the rapid accumulation of lactate at the early stage accompanied by the subsequent relief. As expected, this sensing system is able to provide a novel strategy for effective acquisition and rapid detection of essential biomarkers in sweat.

Preoperative body composition measured by bioelectrical impedance analysis can predict pancreatic fistula after pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains one of the most severe complications after pancreatic surgery. The methods for predicting pancreatic fistula are limited. We aimed to investigate the predictive value of body composition parameters measured by preoperative bioelectrical impedance analysis (BIA) on the development of POPF. METHODS: A total of 168 consecutive patients undergoing pancreatic surgery from March 2022 to December 2022 at our institution were included in the study and randomly assigned at a 3:2 ratio to the training group and the validation group. All data, including previously reported risk factors for POPF and parameters measured by BIA, were collected. Risk factors were analyzed by univariable and multivariable logistic regression analysis. A prediction model was established to predict the development of POPF based on these parameters. RESULTS: POPF occurred in 41 of 168 (24.4%) patients. In the training group of 101 enrolled patients, visceral fat area (VFA) (odds ratio [OR] = 1.077, P = 0.001) and fat mass index (FMI) (OR = 0.628, P = 0.027) were found to be independently associated with POPF according to multivariable analysis. A prediction model including VFA and FMI was established to predict the development of POPF with an area under the receiver operating characteristic curve (AUC) of 0.753. The efficacy of the prediction model was also confirmed in the internal validation group (AUC 0.785, 95% CI 0.659-0.911). CONCLUSIONS: Preoperative assessment of body fat distribution by BIA can predict the risk of POPF after pancreatic surgery.

The utilization of chitosan/Bletilla striata hydrogels to elevate anti-adhesion, anti-inflammatory and pro-angiogenesis properties of polypropylene mesh in abdominal wall repair.

Polypropylene (PP) mesh is commonly used in abdominal wall repair due to its ability to reduce the risk of organ damage, infections and other complications. However, the PP mesh often leads to adhesion formation and does not promote functional tissue repair. In this study, we synthesized one kind of aldehyde Bletilla striata polysaccharide (BSPA) modified chitosan (CS) hydrogel based on Schiff base reaction. The hydrogel exhibited a porous network structure, a highly hydrophilic surface and good biocompatibility. We wrapped the PP mesh inside the hydrogel and evaluated the performance of the resulting composites in a bilateral 1 × 1.5 cm abdominal wall defect model in rats. The results of gross observation, histological staining and immunohistochemical staining demonstrated the positive impact of the CS hydrogel on anti-adhesion and wound healing effects. Notably, the addition of BSPA to the CS hydrogel further improved the performance of the composites in vivo, promoting wound healing by enhancing collagen deposition and capillary rearrangement. This study suggested that the BSPA-modified CS hydrogel significantly promoted the anti-adhesion, anti-inflammatory and pro-angiogenesis properties of PP meshes during the healing process. Overall, this work offers a novel approach to the design of abdominal wall repair patches.

Exploring the Water-Soil-Crop Dynamic Process and Water Use Efficiency of Typical Irrigation Units in the Agro-Pastoral Ecotone of Northern China.

Groundwater resources serve as the primary source of water in the agro-pastoral ecotone of northern China, where scarcity of water resources constrains the development of agriculture and animal husbandry. As a typical rainfed agricultural area, the agro-pastoral ecotone in Inner Mongolia is entirely dependent on groundwater for agricultural irrigation. Due to the substantial groundwater consumption of irrigated farmland, groundwater levels have been progressively declining. To obtain a sustainable irrigation pattern that significantly conserves water, this study faces the challenge of unclear water transport relationships among water, soil, and crops, undefined water cycle mechanism in typical irrigation units, and water use efficiency, which was not assessed. Therefore, this paper, based on in situ experimental observations and daily meteorological data in 2022-2023, utilized the DSSAT model to explore the growth processes of potato, oat, alfalfa, and sunflower, the soil water dynamics, the water balance, and water use efficiency, analyzed over a typical irrigation area. The results indicated that the simulation accuracy of the DSSAT model was ARE < 10%, nRMSE/% < 10%, and R2 ≥ 0.85. The consumption of the soil moisture during the rapid growth stage for the potatoes, oats, alfalfa, and sunflower was 7-13% more than that during the other periods, and the yield was 67,170, 3345, 6529, and 4020 kg/ha, respectively. The soil evaporation of oat, potato, alfalfa, and sunflower accounted for 18-22%, 78-82%; 57-68%, and 32-43%, and transpiration accounted for 40-44%, 56-60%, 45-47%, and 53-55% of ETa (333.8 mm-369.2 mm, 375.2 mm-414.2 mm, 415.7 mm-453.7 mm, and 355.0 mm-385.6 mm), respectively. It was advised that irrigation water could be appropriately reduced to decrease ineffective water consumption. The water use efficiency and irrigation water use efficiency for potatoes was at the maximum amount, ranging from 16.22 to 16.62 kg/m3 and 8.61 to 10.81 kg/m3, respectively, followed by alfalfa, sunflowers, and oats. For the perspective of water productivity, it was recommended that potatoes could be extensively cultivated, alfalfa planted appropriately, and oats and sunflowers planted less. The findings of this study provided a theoretical basis for efficient water resource use in the agro-pastoral ecotone of Northern China.

Experimental confirmation and bioinformatics reveal biomarkers of immune system infiltration and hypertrophy ligamentum flavum.

Background: Hypertrophy ligamentum flavum is a prevalent chronic spinal condition that affects middle-aged and older adults. However, the molecular pathways behind this disease are not well comprehended. Objective: The objective of this work is to implement bioinformatics techniques in order to identify crucial biological markers and immune infiltration that are linked to hypertrophy ligamentum flavum. Further, the study aims to experimentally confirm the molecular mechanisms that underlie the hypertrophy ligamentum flavum. Methods: The corresponding gene expression profiles (GSE113212) were selected from a comprehensive gene expression database. The gene dataset for hypertrophy ligamentum flavum was acquired from GeneCards. A network of interactions between proteins was created, and an analysis of functional enrichment was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. An study of hub genes was performed to evaluate the infiltration of immune cells in patient samples compared to tissues from the control group. Finally, samples of the ligamentum flavum were taken with the purpose of validating the expression of important genes in a clinical setting. Results: Overall, 27 hub genes that were differently expressed were found through molecular biology. The hub genes were found to be enriched in immune response, chemokine-mediated signaling pathways, inflammation, ossification, and fibrosis processes, as demonstrated by GO and KEGG studies. The main signaling pathways involved include the TNF signaling pathway, cytokine-cytokine receptor interaction, and TGF-ß signaling pathway. An examination of immunocell infiltration showed notable disparities in B cells (naïve and memory) and activated T cells (CD4 memory) between patients with hypertrophic ligamentum flavum and the control group of healthy individuals. The in vitro validation revealed markedly elevated levels of ossification and fibrosis-related components in the hypertrophy ligamentum flavum group, as compared to the normal group. Conclusion: The TGF-ß signaling pathway, TNF signaling pathway, and related hub genes play crucial roles in the progression of ligamentum flavum hypertrophic. Our study may guide future research on fibrosis of the ligamentum flavum.

Deciphering the brain-gut axis: elucidating the link between cerebral cortex structures and functional gastrointestinal disorders via integrated Mendelian randomization.

Background: Observational studies have suggested associations between functional gastrointestinal disorders (FGIDs) and variations in the cerebral cortex. However, the causality of these relationships remains unclear, confounded by anxiety and depression. To clarify these causal relationships and explore the mediating roles of anxiety and depression, we applied univariate, multivariable, and mediation Mendelian randomization (MR) analyses. Method: We utilized genome-wide association study (GWAS) summary data from the FinnGen database and the ENIGMA consortium, identifying genetic variants associated with irritable bowel syndrome (IBS), functional dyspepsia (FD), and cerebral cortex structures. Data on anxiety and depression came from FinnGen and a large meta-analysis. Utilizing a bidirectional univariate MR approach, we explored correlations between FD, IBS, and cortex variations. Then, independent effects were assessed through multivariable MR. A meta-analysis of these results, incorporating data from two cohorts, aimed to increase precision. We also explored the potential mediating roles of anxiety and depression. Results: Our findings indicate a negative causal correlation between FD and the thickness of the rostral anterior cingulate cortex (rACC) across both global and regional adjustments (ß = -0.142, 95% confidence interval (CI): -0.209 to-0.074, P.FDR = 0.004; ß = -0.112, 95%CI: -0.163 to-0.006, P.FDR = 0.003) and a positive causal correlation with the globally adjusted thickness of the superior frontal gyrus (SFG) (ß = 0.107, 95%CI: 0.062 to 0.153, P.FDR = 0.001). The causal correlation with the rACC persisted after multiple variable adjustments (ß = -0.137, 95% CI: -0.187 to-0.087, P.FDR = 1.81 × 10-5; ß = -0.109, 95%CI: -0.158 to-0.06, P.FDR = 0.002). A significant causal association was found between globally adjusted surface area of the caudal anterior cingulate cortex (cACC) and IBS (odds ratio = 1.267, 95%CI: 1.128 to 1.424, P.FDR = 0.02). The analysis showed that neither anxiety nor depression mediated the relationship between FGIDs and cerebral cortex structures. Conclusion: Our research provides significant MR evidence of a bidirectional causal relationship between FGIDs and the cerebral cortex structures. This evidence not only confirms the two-way communication along the brain-gut axis but also illuminates the underlying pathophysiology, paving the way for identifying potential therapeutic approaches.

Optimizing Epoxy Interfacial Bonding Properties and Failure Mechanism between Carbon Textile-Reinforced Mortar Composites and Concrete Substrates.

Textile-reinforced mortar (TRM) composites have been extensively utilized in building reinforcement due to their exceptional mechanical properties. The weakest link in the entire structure is the interface between the TRM composites and the concrete; however, it plays a crucial role in effectively transferring stress. Researchers have taken measures to improve the strength of the interface, but the results are relatively scattered. In this paper, the surface treatment of the substrate, the thickness of the surfactant, and the physical doping of the surfactant on the interfacial bonding strength of the concrete were comparatively studied. The results demonstrate that the sandblasting treatment on the surface of the concrete enhances the bonding area between the mortar and the concrete of the reinforcement layer, leading to a 50% increase in the bending resistance of the structure. When the surfactant thickness increases to 0.5 kg/m2, more surfactants penetrate the mortar and concrete. This significantly inhibits the occurrence of cracks in the structure. The addition of 2.5% Al2O3 nanomaterials to the surfactant diminishes the shrinkage rate of the curing process, enhances the impact toughness, and improves the flexural and compressive properties of the bonding layer. The ultimate load of the structure increases by 65%. Physical doping of the surfactant is the most effective measure with the most apparent improvement result. It significantly enhances the bonding strength of the interface and can be widely used in construction.

Electrosynthesis of an Improbable Directly Bonded Phosphorene-Fullerene Heterodimensional Hybrid toward Boosted Photocatalytic Hydrogen Evolution.

Phosphorene and fullerene are representative two-dimensional (2D) and zero-dimensional (0D) nanomaterials respectively, constructing their heterodimensional hybrid not only complements their physiochemical properties but also extends their applications via synergistic interactions. This is however challenging because of their diversities in dimension and chemical reactivity, and theoretical studies predicted that it is improbable to directly bond C60 onto the surface of phosphorene due to their strong repulsion. Here, we develop a facile electrosynthesis method to synthesize the first phosphorene-fullerene hybrid featuring fullerene surface bonding via P-C bonds. Few-layer black phosphorus nanosheets (BPNSs) obtained from electrochemical exfoliation react with C602- dianion prepared by electroreduction of C60, fulfilling formation of the "improbable" phosphorene-fullerene hybrid (BPNS-s-C60). Theoretical results reveal that the energy barrier for formation of [BPNS-s-C60]2- intermediate is significantly decreased by 1.88 eV, followed by an oxidization reaction to generate neutral BPNS-s-C60 hybrid. Surface bonding of C60 molecules not only improves significantly the ambient stability of BPNSs, but also boosts dramatically the visible light and near-infrared (NIR) photocatalytic hydrogen evolution rates, reaching 1466 and 1039 µmol h-1 g-1 respectively, which are both the highest values among all reported BP-based metal-free photocatalysts.

Trends and cross-country inequalities in the global burden of osteoarthritis, 1990-2019: A population-based study.

OBJECTIVE: To evaluate the trends and cross-country inequalities of global osteoarthritis (OA) burden over the last 30 years, and further predicted its changes to 2035. METHODS: The estimates and 95 % uncertainty intervals (UIs) for incidence, prevalence, and disability-adjusted life-years (DALYs) of OA were extracted from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We described OA epidemiology at global, regional, and national levels, analyzed 1990-2019 trends in OA burden from overall, local, and multi-dimension scopes, decomposed OA burden according to population size, age structure, and epidemiologic changes, quantified cross-country inequalities in OA burden using standard health equity methods recommended by World Health Organization, and predicted changes of OA burden to 2035. RESULTS: GBD 2019 estimated 527,811,871 (95 % UIs: 478,667,549 to 584,793,491) prevalent cases, 41,467,542 (95 % UIs: 36,875,471 to 46,438,409) incident cases and 18,948,965 (95 % UIs: 9,571,298 to 37,659,660) DALYs cases of OA worldwide in 2019, with the highest cases in East Asia and highest age-standardized rate (ASR) in high-income North America. The global burden of OA increased overall from 1990 to 2019 with the fastest growth observed in the first decade of the 21st century. Decomposition analysis revealed that OA knee (62.78 %), women (60.47 %), and middle sociodemographic index (SDI) quintile (32.35 %) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. A significant increase in SDI-related inequalities was detected, and the gap in DALYs between the highest SDI country and the lowest SDI country increased from 179.5 [95 % confidence interval (CI): 149.3-209.8] per 100,000 in 1990 to 341.9 (95 % CI: 309.5-374.4) per 100,000 in 2019. Notably, although the ASR of incidence, prevalence, and DALYs of OA was predicted to decrease annually from 2020 to 2035, the case number of these metrics was predicted to keeping increasing, with predicted values of 52,870,737 [95 % credible interval (Crl): 39,330,063 to 66,411,411], 727,532,373 (95 % Crl: 542,765,783 to 912,298,962), and 25,986,983 (95 % Crl: 19,216,928 to 32,757,038) in 2035, respectively. CONCLUSIONS: As a major public health issue, the global burden of OA showed an overall increasing trend from 1990 to 2019, which was primarily driven by population growth and aging. Countries with high SDI shouldered disproportionately high OA burden, and the SDI-related inequalities across countries exacerbated over time. This study highlighted great challenges in the control and management of OA, including both growing case number and distributive inequalities worldwide, which may be instructive for better making public health policy and reasonably allocating medical source.

Global associations between long-term exposure to PM2.5 constituents and health: A systematic review and meta-analysis of cohort studies.

Existing studies on the most impactful component remain controversial, hindering the optimization of future air quality standards that concerns particle composition. We aimed to summarize the health risk associated with PM2.5 components and identify those components with the greatest health risk. We performed a meta-analysis to quantify the combined health effects of PM2.5 components, and used the meta-smoothing to produce the pooled concentration-response (C-R) curves. Out of 8954 initial articles, 80 cohort studies met the inclusion criteria, including a total of 198.08 million population. The pooled C-R curves demonstrated approximately J-shaped association between total mortality and exposure to BC, and NO3-, but U-shaped and inverted U-shaped relationship withSO42- and OC, respectively. In addition, this study found that exposure to various elements, including BC,SO42-NO3-, NH4+, Zn, Ni, and Si, were significantly associated with an increased risk of total mortality, with Ni presenting the largest estimate. And exposure to NO3-, Zn, and Si was positively associated with an increased risk of respiratory mortality, while exposure to BC, SO42-, and NO3- showed a positive association with risk of cardiovascular mortality. For health outcome of morbidity, BC was notably associated with a higher incidence of asthma, type 2 diabetes and stroke. Subgroup analysis revealed a higher susceptibility to PM2.5 components in Asia compared to Europe and North America, and females showed a higher vulnerability. Given the significant health effects of PM2.5 components, governments are advised to introduce them in regional monitoring and air quality control guidelines. ENVIRONMENTAL IMPLICATION: PM2.5 is a complex mixture of chemical components from various sources, and each component has unique physicochemical properties and uncertain toxicity, posing significant threat to public health. This study systematically reviewed cohort studies on the association between long-term exposure to 13 PM2.5 components and the risk of morbidity and mortality. And we applied the meta-smoothing approach to establish the pooled concentration-response associations between PM2.5 components and mortality globally. Our findings will provide strong support for PM2.5 components monitoring and the improvement of air quality-related regulations. This will aid in helping to enhance health intervention strategies and mitigating public exposure to detrimental particulate matter.

Multimorbidity and emergency hospitalisations during hot weather.

BACKGROUND: People with chronic diseases are a commonly listed heat-vulnerable group in heat-health action plans. While prior research identifies multiple health conditions that may increase vulnerability to ambient heat, there is minimal evidence regarding the implications of multimorbidity (two or more chronic diseases). METHODS: From the statewide hospital registry of Queensland, Australia, we identified people aged ≥15 years who had emergency hospitalisation(s) between March 2004 and April 2016 and previously had 0, 1, 2, or ≥3 of five chronic diseases: cardiovascular disease, diabetes, mental disorders, asthma/COPD, and chronic kidney disease. We conducted time-stratified case-crossover analyses to estimate the odds ratio of hospitalisations associated with ambient heat exposure in people with different numbers, types, and combinations of chronic diseases. Ambient heat exposure was defined as a 5 °C increase in daily mean temperature above the median. FINDINGS: There were 2,263,427 emergency hospitalisations recorded (48.7% in males and 51.3% in females). When the mean temperature increased, hospitalisation odds increased with chronic disease number, particularly in older persons (≥65 years), males, and non-indigenous people. For instance, in older persons with 0, 1, 2, or ≥3 chronic diseases, the odds ratios associated with ambient heat exposure were 1.00 (95% confidence interval: 0.96, 1.04), 1.06 (1.02, 1.09), 1.08 (1.02, 1.14), and 1.13 (1.07, 1.19), respectively. Among the chronic diseases, chronic kidney disease, and asthma/COPD, either existing alone, together, or in combination with other diseases, were associated with the highest odds of hospitalisations under ambient heat exposure. INTERPRETATION: While individuals with multimorbidity are considered in heat-health action plans, this study suggests the need to consider specifically examining them as a distinct and vulnerable subgroup. FUNDING: Wellcome.

Heat and health of occupational workers: a short summary of literature.

Globally, occupational workers suffer various health impacts due to extreme heat. In this short review, we examine the literature discussing health impacts of heat on occupational workers, and then discuss certain individual and institutional measures needed to address the problem. Though the available literature in the recent decade discusses health impacts of heat on workers as various heat-related illnesses, we found very few studies examining how occupational workers suffer from issues concerning cardiovascular health, neurological health, respiratory health, and mental health. In this regard, we highlight the need for more studies to examine how occupational workers exposed to extreme heat conditions suffer from fatal health issues like cardiovascular attack, brain stroke, and other ailments impacting vital organs of the body. Occupational workers across the world should be made aware of measures to protect themselves from extreme heat. Further, countries should develop occupational heat safety guidelines with statutory effect.

Efforts to promote osteogenesis-angiogenesis coupling for bone tissue engineering.

Repair of bone defects exceeding a critical size has been always a big challenge in clinical practice. Tissue engineering has exhibited great potential to effectively repair the defects with less adverse effect than traditional bone grafts, during which how to induce vascularized bone formation has been recognized as a critical issue. Therefore, recently many studies have been launched to attempt to promote osteogenesis-angiogenesis coupling. This review summarized comprehensively and explored in depth current efforts to ameliorate the coupling of osteogenesis and angiogenesis from four aspects, namely the optimization of scaffold components, modification of scaffold structures, loading strategies for bioactive substances, and employment tricks for appropriate cells. Especially, the advantages and the possible reasons for every strategy, as well as the challenges, were elaborated. Furthermore, some promising research directions were proposed based on an in-depth analysis of the current research. This paper will hopefully spark new ideas and approaches for more efficiently boosting new vascularized bone formations.

Correlation Between Serum 1,25(OH)2D3, Serum Phosphorus, and Parathyroid Hormone and Parathyroid Function After Central Lymph Node Dissection in Patients with Papillary Thyroid Carcinoma.

This work was to demonstrate the relationship between serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), serum phosphorus (SP), and parathyroid hormone (PTH) and parathyroid function after central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC). 200 PTC patients after CLND were included, who were rolled into a control group (CG) (n = 89 cases without hypoparathyroidism) and an observation group (OG) (n = 111 cases with complicated hypoparathyroidism). The 1,25(OH)2D3, SP, and PTH levels were detected, and the diagnostic effect of these indicators was assessed. The serum PTH levels of patients in CG after surgery were normal relative to those before surgery, while the serum PTH of patients in OG was relatively lower. 1,25(OH)2D3 concentration of patients in OG was also inferior to CG, while the SP level was superior (P < 0.05). Hypoparathyroidism was positively correlated with serum PTH (r = 0.382) and 1,25(OH)2D3 (r = 0.321) and negatively correlated with SP (r = - 0.211). The area under the curve (AUC) (0.893), sensitivity (90.83%), and specificity (94.77%) of the joint diagnosis of 1,25(OH)2D3 + SP + PTH were greatly superior to those of the single diagnosis and the pairwise diagnosis with the three indicators (P < 0.05). Hypoparathyroidism in patients with PTC after CLND surgery was positively correlated with 1,25(OH)2D3 and PTH and negatively correlated with SP concentration. In addition, the combination diagnosis of 1,25(OH)2D3, PTH, and SP worked well.

Projecting heat-related cardiovascular mortality burden attributable to human-induced climate change in China.

BACKGROUND: Cardiovascular disease (CVD) has been found to be particularly vulnerable to climate change and temperature variability. This study aimed to assess the extent to which human-induced climate change contributes to future heat-related CVD burdens. METHODS: Daily data on CVD mortality and temperature were collected in 161 Chinese communities from 2007 to 2013. The association between heat and CVD mortality was established using a two-stage time-series design. Under the natural forcing, human-induced, and combined scenarios, we then separately projected excess cause-/age-/region-/education-specific mortality from future high temperature in 2010-2100, assuming no adaptation and population changes. FINDINGS: Under shared socioeconomic pathway with natural forcing scenario (SSP2-4.5-nat), heat-related attributable fraction of CVD deaths decreased slightly from 3.3% [95% empirical confidence interval (eCI): 0.3, 5.8] in the 2010s to 2.8% (95% eCI: 0.1, 5.2) in the 2090s, with relative change of -0.4% (95% eCI: -0.8, 0.0). However, for combined natural and human-induced forcings, this estimate would surge to 8.9% (95% eCI: 1.5, 15.7), 14.4% (95% eCI: 1.5, 25.3), 21.3% (95% eCI: -0.6, 39.4), and 28.7% (95% eCI: -3.3, 48.0) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. When excluding the natural forcing, the number of human-induced heat-related CVD deaths would increase from approximately eight thousand (accounting for 31% of total heat-related CVD deaths) in the 2010s to 33,052 (68%), 63,283 (80%), 101,091 (87%), and 141,948 (90%) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. Individuals with stroke, females, the elderly, people living in rural areas, and those with lower education level would exhibit heightened susceptibility to future high temperature. In addition, Southern and Eastern regions of China were expected to experience a faster increase in heat-related attributable fraction of CVD deaths. INTERPRETATION: Human activities would significantly amplify the future burden of heat-related CVD. Our study findings suggested that active adaptation and mitigation measures towards future warming could yield substantial health benefits for the patients with CVD. FUNDING: National Natural Science Foundation of China.

Prognostic and onco-immunological value of immune-related eRNAs-driven genes in lung adenocarcinoma.

BACKGROUND: We aimed to comprehensively analyze the clinical value of immune-related eRNAs-driven genes in lung adenocarcinoma (LUAD) and find the potential biomarkers for prognosis and therapeutic response to improve the survival of this malignant disease. MATERIALS AND METHODS: Pearson's correlation analysis was performed to identify the immune-related eRNAs-driven genes. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were used to construct this prognostic risk signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to investigate the underlying molecular mechanism. The single sample gene set enrichment analysis (ssGSEA) algorithm was conducted to evaluate the immune status based on the signature. The quantitative real-time PCR (qRT-PCR) analysis was performed to evaluate the expression value of the signature genes between LUAD tissues and adjacent lung tissues. RESULTS: Five immune-related eRNAs-driven genes (SHC1, GDF10, CCL14, FYN, and NOD1) were identified to construct a prognostic risk signature with favorable predictive capacity. The patients with high-risk scores based on the signature were significantly associated with the malignant clinical features compared with those with low-risk scores. Kaplan-Meier analysis demonstrated that the sample in the low-risk group had a prolonged survival compared with those in the high-risk group. This risk signature was validated to have a promising predictive capacity and reliability in diverse clinical situations and independent cohorts. The functional enrichment analysis demonstrated that humoral immune response and intestinal immune network for IgA production pathway might be the underlying molecular mechanism related to the signature. The proportion of the vast majority of immune infiltrating cells in the high-risk group was significantly lower than that in the low-risk group, and the immunotherapy response rate in the low-risk group was significantly higher than that in the high-risk group. Moreover, BI-2536, sepantronium bromide, and ULK1 were the potential drugs for the treatment of patients with higher risk scores. Finally, the experiment in vivo and database analysis indicated that CCL14, FYN, NOD1, and GDF10 are the potential LUAD suppressor and SHC1 is a potential treatment target for LUAD. CONCLUSION: Above all, we constructed a prognostic risk signature with favorable predictive capacity in LUAD, which was significantly associated with malignant features, immunosuppressive tumor microenvironment, and immunotherapy response and may provide clinical benefit in clinical decisions.