Sex differences in impact of cumulative systolic blood pressure from childhood to adulthood on albuminuria in midlife: a 30-year prospective cohort study.

BACKGROUND AND OBJECTIVES: Albuminuria is recognized as being a predictor of cardiovascular and renal disease. We aimed to identify the impact of the long-term burden and trends of systolic blood pressure on albuminuria in midlife, as well as to explore sex differences concerning this relationship. METHODS: This longitudinal study consisted of 1,683 adults who had been examined 4 or more times for blood pressure starting in childhood, with a follow-up time period of 30 years. The cumulative effect and longitudinal trend of blood pressure were identified by using the area under the curve (AUC) of individual systolic blood pressure measurement with a growth curve random effects model. RESULTS: Over 30 years of follow-up, 190 people developed albuminuria, including 53.2% males and 46.8% females (aged 43.39 ± 3.13 years in the latest follow-up). The urine albumin-to-creatinine ratio (uACR) values increased as the total and incremental AUC values increased. Additionally, women had a higher albuminuria incidence in the higher SBP AUC groups than men do (13.3% for men vs. 33.7% for women). Logistic regression showed that the ORs of albuminuria for males and females in the high total AUC group were 1.34 (0.70-2.60) and 2.94 (1.50-5.74), respectively. Similar associations were found in the incremental AUC groups. CONCLUSIONS: Higher cumulative SBP was correlated with higher uACR levels and a risk of albuminuria in middle age, especially in women. The identification and control of cumulative SBP levels from an early age may assist in reducing the incidences of renal and cardiovascular disease for individuals in later life.

Continuous Chemiluminescence Measurements of Dissolved Nitric Oxide (NO) and Nitrogen Dioxide (NO2) in the Ocean Surface Layer of the East China Sea.

Nitric oxide (NO) is a short-lived intermediate of the oceanic nitrogen cycle, and it is produced by biological and photochemical processes in the ocean. Nitrogen dioxide (NO2) is a reactive atmospheric compound which has not been determined in the ocean so far. Here, we present the setup and validation of a novel continuous underway measurement system to measure dissolved NO and NO2 in the surface ocean. The system consists of a seawater/gas equilibration component coupled to a chemiluminescence detector. It was successfully deployed during a 12 day cruise to the East China Sea in May 2018. Dissolved NO and NO2 surface concentrations ranged from

Risk factors for electrocardiographic left ventricular hypertrophy in a young Chinese general population: the Hanzhong adolescent cohort study.

BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG-LVH) is a common manifestation of preclinical cardiovascular disease. The present study aimed to investigate risk factors for ECG-LVH and its prevalence in a cohort of young Chinese individuals. METHODS: (1) A total of 1515 participants aged 36-45 years old from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine risk factors for ECG-LVH and its prevalence. (2) A total of 235 participants were recruited from the same cohort in 2013 and were followed up in 2017. Longitudinal analysis was used to determine the predictors of LVH occurrence over the 4-year period. We used multivariable logistic regression models to calculate OR and 95% CIs and to analyze risk factors for ECG-LVH. RESULTS: In the cross-sectional analysis, the prevalence of LVH diagnosed by the Cornell voltage-duration product in the overall population and the hypertensive population was 4.6% and 8.8%, respectively. The logistic regression results shown that female sex [2.611 (1.591-4.583)], hypertension [2.638 (1.449-4.803)], systolic blood pressure (SBP) [1.021 (1.007-1.035)], serum uric acid (SUA) [1.004 (1.001-1.006)] and carotid intima-media thickness (CIMT) [67.670 (13.352-342.976)] were significantly associated with the risk of LVH (all P < 0.05). In the longitudinal analysis, fasting glucose [1.377 (1.087-1.754)], SBP [1.046 (1.013-1.080)] and female sex [1.242 (1.069-1.853)] were independent predictors for the occurrence of LVH in the fourth year of follow-up. CONCLUSIONS: Our study suggested that female sex, hypertension, SBP, SUA and CIMT were significantly associated with the risk of LVH in young people. In addition, fasting glucose, SBP and female sex are independent predictors of the occurrence of LVH in a young Chinese general population.

Long-term burden of higher body mass index from childhood on adult cardiometabolic biomarkers: A 30-year cohort study.

BACKGROUND AND AIMS: Data are limited regarding the association between long-term burden of higher body mass index (BMI) from childhood and cardiometabolic biomarkers. METHODS AND RESULTS: A total of 1553 individuals aged 6-15 years, who were examined 4 or more times for BMI since childhood and followed for 30 years were included in our analysis. Total area under the curve (AUCt) and incremental AUC (AUCi) were calculated as the long-term burden and trends of BMI. Cardiometabolic biomarkers including serum uric acid (SUA), fasting blood-glucose (FBG), and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) were obtained from venous blood samples. The results showed a positive association of BMI AUCt and AUCi with cardiometabolic biomarkers. After adjusting for demographic variables, the AUCt and AUCi of BMI were significantly associated with a higher level of SUA (ß = 3.71; 2.87), FBG (ß = 0.09; 0.09), and TG/HDL-C (ß = 0.14; 0.11). We performed further studies after dividing subjects into four groups according to AUCt and AUCi of BMI by quartiles. Compared with the lowest quartile group, the highest quartile group had significantly increased risk ratios of hyperuricemia (RR = 2.01; 1.74), type 2 diabetes mellitus (RR = 8.18; 3.96), and high-risk TG/HDL-C (RR = 4.05; 3.26). CONCLUSION: Our study identifies all subjects' BMI growth curve from childhood and indicates that the long-term burden of higher BMI significantly increases the cardiometabolic risk, and the impact of excessive body weight on cardiometabolic health originates in early life. We emphasize the importance of weight control from childhood for cardiometabolic health.

Predictive Role of Child-To-Adult Blood Pressure Trajectories for Incident Metabolic Syndrome: 30-Year Hanzhong Adolescent Hypertension Study.

OBJECTIVE: The relationship between child-to-adult blood pressure (BP) trajectories and metabolic syndrome (MetS) is unknown. We aimed to determine the predictive role of BP trajectories for incident MetS and its components. METHODS: The prospective Hanzhong Adolescent Hypertension study began in 1987 and included 2692 participants free of MetS at baseline with at least 3 BP measurements available from 1987 to 2017. RESULTS: The systolic BP (SBP) trajectory patterns were grouped as normal (class 1, 18.7%), high normal (class 2, 60.3%), prehypertensive (class 3, 13.1%), stage 1 hypertensive (class 4, 5.7%), and stage 2 hypertensive (class 5, 2.2%). Compared with those in the normal group, individuals in classes 2 to 5 had significantly higher risks of MetS (all Ps < .05), and those with hypertension had more than an 8-fold higher risk of MetS (both P < .05). The fully adjusted risk ratios (RRs) of central obesity increased significantly in a stepwise manner as the SBP trajectory group increased from class 1 to class 5 (P < .05). Compared with those with a normal SBP trajectory, participants in the prehypertensive group and stage 1 and stage 2 hypertensive groups had significantly higher RRs for high-risk triglycerides after full adjustment (RR = 1.89 [1.22-2.94]; RR = 3.61 [2.16-6.02]; and RR = 3.22 [1.52-6.84], respectively). CONCLUSION: Our study suggests that BP trajectories are predictive of incident MetS outcomes. Early detection of hypertension or modest elevations in BP is crucial. The stage of hypertension based on SBP level showed a greater association with central obesity.

Association of body mass index changes from childhood to adulthood with dyslipidemia in adults: Hanzhong adolescent cohort study.

BACKGROUND: Dyslipidemia is a disorder of lipid metabolism and associated with insulin resistance. The relationship between longitudinal body mass index (BMI) changes from childhood to adulthood and long-term dyslipidemia was explored in this study. METHODS: We assessed the longitudinal relationship between BMI changes since childhood and dyslipidemia among 1738 participants in rural areas of Hanzhong City, Shaanxi. All participants were initially examined between the ages of 6 and 15 years in 1987 and were reexamined in 1995, 2013 and 2017; the total follow-up duration was 30 years. Anthropometric measurements and blood biochemistry indexes were measured. RESULTS: We found that gradual progression of normal weight to overweight (OR = 1.65; 95% CI = 1.27, 2.15) or persistent overweight (OR = 2.45; 95% CI = 1.52, 3.96) from childhood to adulthood was associated with an increased risk of dyslipidemia in adulthood. And these risks were largely disappeared if the overweight or obesity during childhood was resolved by adulthood. The higher the BMI in adulthood and the younger the age at which overweight begins, the higher the risk of dyslipidemia. CONCLUSIONS: Early weight loss and any degree of weight loss from childhood to adulthood can help improve dyslipidemia in adulthood. We further emphasize the importance of weight management and control in public health primary prevention.

Salvianolic acid B combined with mesenchymal stem cells contributes to nucleus pulposus regeneration.

PURPOSE: To investigate whether salvianolic acid B is able to enhance repair of degenerated intervertebral discs by mesenchymal stem cells (MSCs) through the promotion of MSC differentiation into nucleus pulposus cells in a nucleus-pulposus-like environment and by enhancing the trophic effect of MSCs on residual nucleus pulposus cells (mediated by transforming growth factor-ß1). MATERIALS AND METHODS: Successful intervertebral disc degeneration models, established by aspiration of the nucleus pulposus in New Zealand white rabbits, were randomly divided into eight groups: Group A was treated with MSC transplantation. Group B was treated with MSC transplantation and salvianolic acid B, with the subgroups B1, B2, B3, and B4 receiving 0.01 mg/L, 0.1 mg/L, 1 mg/L, and 10 mg/L salvianolic acid B, respectively. Groups C and D were treated with phosphate buffer saline and sham graft, respectively. Group E was the normal control group. At the end of week 8, the type II collagen, proteoglycan, transforming growth factor-ß1, and water contents in each group were examined by semi-quantitative immunohistochemistry, spectrophotometry, enzyme-linked immunosorbent assay, and magnetic resonance, respectively. RESULTS: The content of type II collagen, proteoglycan, transforming growth factor-ß1, and water in groups B3 and B4 were significantly higher than those in group A (p < 0.01). CONCLUSIONS: Salvianolic acid B (1 mg/L to 10 mg/L) plus MSC transplantation was more effective in repairing degenerated intervertebral discs than was stem cell transplantation alone.

Effect of Salt Intake on Serum Glucagon-Like Peptide-1 Levels in Normotensive Salt-Sensitive Subjects.

BACKGROUND/AIMS: Excess dietary salt is a critical risk factor of salt-sensitive hypertension. Glucagon-like peptide-1 (GLP-1) , a gut incretin hormone, conferring benefits for blood pressure by natriuresis and diuresis. We implemented a randomized trial to verify the effect of altered salt intake on serum GLP-1 level in human beings. METHODS: The 38 subjects were recruited from a rural community of Northern China. All subjects were sequentially maintained a baseline diet period for 3 days, a low-salt diet period for 7 days (3.0g/day of NaCl) , and a high-salt diet period for additional 7 days (18.0g/day of NaCl). RESULTS: Serum GLP-1 level increased significantly with the change from the baseline period to the low-salt diet period and decreased with the change from the low-salt to high-salt diet in normotensive salt-sensitive (SS) but not salt-resistant (SR) individuals. There was a significant inverse correlation between the serum GLP-1 level and the MAP in SS subjects. Inverse correlation between the serum GLP-1 level and 24-h urinary sodium excretion was also found among different dietary interventions in SS subjects. CONCLUSIONS: Our study indicates that variations in dietary salt intake affect the serum GLP-1 level in normotensive salt-sensitive Chinese adults.

The Role of Uric Acid in Hypertension of Adolescents, Prehypertension and Salt Sensitivity of Blood Pressure.

Uric acid is the end product of purine metabolism. Metabolic disorders of uric acid are associated with many disease states. Substantial evidence suggests the possible role of uric acid as a mediator of high blood pressure. Elevated uric acid is closely associated with new onset essential hypertension in adolescents and prehypertension; and urate-lowering agents can significantly improve these early stages of hypertension. Uric acid also influences salt sensitivity of blood pressure through two phases. Local renin-angiotensin-aldosterone system activation initiates renal damage, arteriolopathy, and endothelium dysfunction, which is followed by the dysregulation of sodium homeostasis, thereby leading to increased salt sensitivity. In this review we summarize the available evidence to contribute to a better understanding of the casual relationship between uric acid and early or intermediate stages of hypertension. We hope our review can contribute to the prevention of hypertension or provide new insights into a treatment that would slow the progression of hypertension.

A C-type lectin could selectively facilitate bacteria clearance in red swamp crayfish, Procambarus clarkii.

C-type lectins function as pattern recognition receptors and play important roles in the innate immune system of crustaceans. In this study, we reported a new CTL gene (designated as PcLec5) from red swamp crayfish, Procambarus clarkii. PcLec5 was mainly distributed in hepatopancreas, gills and intestine, and the PcLec5 transcripts were up-regulated in all the three tissues after challenge with bacteria Vibrio anguillarum. For further functional analyses, PcLec5 was recombinantly expressed in Escherichia coli and anti-PcLec5 polyclonal antiserum was prepared. The results of bacteria binding assay revealed that PcLec5 could selectively bind to 5 of 9 kinds of bacteria we used and had a tendency to bind to Gram-negative bacteria. Sugar binding assay showed that PcLec5 could bind to peptidoglycan, lipoteichoic acid and lipopolysaccharide, with the highest affinity to LPS. Furthermore, bacteria-clearance experiment showed PcLec5 could selectively facilitate the clearance of injected bacteria in crayfish, and the bacteria-clearance facilitating spectrum of PcLec5 was totally in agreement with its bacteria binding spectrum. These results suggested PcLec5 function as a pattern recognition receptor in crayfish immune system and had certain selectivity on bacteria pathogens.

Efficient and Selective Oxygenation of Cycloalkanes and Alkyl Aromatics with Oxygen through Synergistic Catalysis of Bimetallic Active Centers in Two-Dimensional Metal-Organic Frameworks Based on Metalloporphyrins.

Confined catalytic realms and synergistic catalysis sites were constructed using bimetallic active centers in two-dimensional metal-organic frameworks (MOFs) to achieve highly selective oxygenation of cycloalkanes and alkyl aromatics with oxygen towards partly oxygenated products. Every necessary characterization was carried out for all the two-dimensional MOFs. The selective oxygenation of cycloalkanes and alkyl aromatics with oxygen was accomplished with exceptional catalytic performance using two-dimensional MOF Co-TCPPNi as a catalyst. Employing Co-TCPPNi as a catalyst, both the conversion and selectivity were improved for all the hydrocarbons investigated. Less disordered autoxidation at mild conditions, inhibited free-radical diffusion by confined catalytic realms, and synergistic C-H bond oxygenation catalyzed by second metal center Ni employing oxygenation intermediate R-OOH as oxidant were the factors for the satisfying result of Co-TCPPNi as a catalyst. When homogeneous metalloporphyrin T(4-COOCH3)PPCo was replaced by Co-TCPPNi, the conversion in cyclohexane oxygenation was enhanced from 4.4% to 5.6%, and the selectivity of partly oxygenated products increased from 85.4% to 92.9%. The synergistic catalytic mechanisms were studied using EPR research, and a catalysis model was obtained for the oxygenation of C-H bonds with O2. This research offered a novel and essential reference for both the efficient and selective oxygenation of C-H bonds and other key chemical reactions involving free radicals.

Inhibition of the STIM1/Orai1 Signaling Pathway by Glycine Betaine Mitigates Myocardial Hypertrophy in Spontaneous Hypertension Rats.

Background: Spontaneous hypertension is a leading risk factor for cardiovascular diseases morbidity and mortality. Glycine betaine (GB) is a natural vitamin that has the potential to lower blood pressure. This work attempted to investigate the role and mechanisms of GB in spontaneous hypertension. Methods: Spontaneously hypertensive rats (SHRs) were administrated with 100, 200, or 400 mg/kg of GB by gavage or combined with by injection of lentivirus-mediated STIM1 overexpression vector. The heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart weight/body weight (HW/BW) of rats were monitored. The pathological changes in myocardium were examined by hematoxylin and eosin staining and Masson staining. The expression of genes and proteins was detected by quantitative real-time PCR, western blotting, and immunohistochemistry. Results: GB at 200 and 400 mg/kg reduced the HR, SBP, DBP and HW/BW in SHRs. GB decreased the cross-sectional area and fibrotic area in the myocardium and downregulated the expression of atrial natriuretic peptide (ANP) and ß-myosin heavy chain (ß-MHC) in the myocardium of SHRs. It indicated that GB treatment effectively alleviated myocardial hypertrophy in SHRs. Additionally, GB treatment repressed the expression of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1) in the myocardium of SHRs. STIM1 overexpression reversed GB treatment-mediated inhibition of myocardial hypertrophy in SHRs. Conclusions: In conclusion, GB repressed STIM1/Orai1 signaling pathway, which contributed to alleviating myocardial hypertrophy in SHRs. Thus, our study provides a theoretical basis for GB as an antihypertensive drug.

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid.

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.

Associations of lipid accumulation product, visceral adiposity index, and triglyceride-glucose index with subclinical organ damage in healthy Chinese adults.

Background and aims: Obesity is an independent risk factor for cardiovascular disease development. Here, we aimed to examine and compare the predictive values of three novel obesity indices, lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose (TyG) index, for cardiovascular subclinical organ damage. Methods: A total of 1,773 healthy individuals from the Hanzhong Adolescent Hypertension Study cohort were enrolled. Anthropometric, biochemical, urinary albumin-to-creatinine ratio (uACR), brachial-ankle pulse wave velocity (baPWV), and Cornell voltage-duration product data were collected. Furthermore, the potential risk factors for subclinical organ damage were investigated, with particular emphasis on examining the predictive value of the LAP, VAI, and TyG index for detecting subclinical organ damage. Results: LAP, VAI, and TyG index exhibited a significant positive association with baPWV and uACR. However, only LAP and VAI were found to have a positive correlation with Cornell product. While the three indices did not show an association with electrocardiographic left ventricular hypertrophy, higher values of LAP and TyG index were significantly associated with an increased risk of arterial stiffness and albuminuria. Furthermore, after dividing the population into quartiles, the fourth quartiles of LAP and TyG index showed a significant association with arterial stiffness and albuminuria when compared with the first quartiles, in both unadjusted and fully adjusted models. Additionally, the concordance index (C-index) values for LAP, VAI, and TyG index were reasonably high for arterial stiffness (0.856, 0.856, and 0.857, respectively) and albuminuria (0.739, 0.737, and 0.746, respectively). Lastly, the analyses of continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) demonstrated that the TyG index exhibited significantly higher predictive values for arterial stiffness and albuminuria compared with LAP and VAI. Conclusion: LAP, VAI, and, especially, TyG index demonstrated utility in screening cardiovascular subclinical organ damage among Chinese adults in this community-based sample. These indices have the potential to function as markers for early detection of cardiovascular disease in otherwise healthy individuals.

Ultrasound-guided microwave ablation as a palliative treatment for mycosis fungoides eyelid involvement: A case report.

BACKGROUND: Mycosis fungoides (MF) is a form of lymphoma derived from heterogeneous T cells, and eyelid involvement is extremely rare. The common methods to treat eyelid involvement are radiotherapy and chemotherapy, but their efficacies are limited. Herein, we report a case of advanced-stage MF eyelid involvement, propose ultrasound (US)-guided microwave ablation (MWA) therapy and present a literature review. CASE SUMMARY: A male patient was admitted to our hospital in June 2018 and diagnosed with MF via radiological and histopathological examinations. The patient's condition was not well controlled by various conventional chemotherapies. US-guided MWA was performed to relieve the patient's symptoms and improve his quality of life, showing satisfactory efficacy. CONCLUSION: Eyelid involvement is one of the most troublesome clinical problems for advanced-stage MF patients. This is the first report on the use of US-guided MWA as a palliative therapy for MF eyelid involvement; the treatment successfully relieved the patient's clinical symptoms and reduced his anxiety behaviours. Our study sheds new light on methods for improving the clinical management of eyelid involvement in MF.

Lactobacillus Suppresses Tumorigenesis of Oropharyngeal Cancer via Enhancing Anti-Tumor Immune Response.

Deficiency in T cell-mediated adaptive immunity, such as low CD8+ T cell infiltration, inhibits the immune surveillance, promotes malignant transformation, and facilitates tumor growth. Microbiota dysbiosis diminishes the immune system and contributes to the occurrence of cancer. However, the impact of oral dysbiosis on the occurrence and molecular mechanisms of oropharyngeal cancer (OPC) remains largely unknown. In the current study, we used 4-nitroquinoline-1-oxide (4NQO) to mimic tobacco-related carcinogenesis to generate a murine OPC model and determine the role of microbiota changes in OPC tumorigenesis. Our results showed that the oral flora composition of mice was deregulated during the tumorigenesis of OPC. The abundance of Streptococcus, Veillonella, Muribacter, Rodentibacter, and Gemella was increased, whereas the dominant genus Lactobacillus was gradually decreased with disease progression. We further demonstrated that infiltration of CD8+ T lymphocytes was markedly reduced due to the reduction of Lactobacillus. Supplementation of Lactobacillus increased the infiltration of CD8+ T cells, promoted the expression of IFN-γ and granzyme B, and lessened the OPC progression. Analyzing the metabolites of the Lactobacillus, we demonstrated that Lactobacillus enhanced the anti-tumor immune response by producing acetate in OPC development. Administration of acetate to mice could increase the expression of IFN-γ and IFN-γ-inducible chemokines in tumor tissues by activating GPR43 to promote the infiltration of CD8+ T lymphocytes and substantially delay the development of OPC. Together, our data suggest that dysbiosis of oral microbiota promotes the tumorigenesis of OPC through downregulation of cytotoxic T lymphocytes. Lactobacillus and its metabolite acetate improve the tumor microenvironment, which could be applied in the treatment of OPC.

Metformin alleviates irradiation-induced intestinal injury by activation of FXR in intestinal epithelia.

Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus, which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine.

Early life body mass index trajectories and albuminuria in midlife: A 30-year prospective cohort study.

Background: Albuminuria is a marker of vascular dysfunction and is associated with chronic renal and cardiovascular diseases. Data on the association between the longitudinal patterns of weight change early in life and albuminuria later in life are limited. We aimed to identify the body mass index (BMI) trajectory across a 30-year span and evaluate its association with middle-age albuminuria. Methods: Of the 4623 participants aged 6-18-year-old recruited by Hanzhong Adolescent Hypertension Study cohort in northern China from March 10, 1987 to June 3, 2017, a total of 1,825 participants followed up with 6 visits over 30 years were enrolled. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analyses. Albuminuria was defined as a urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. Findings: Three distinct BMI trajectories were identified: low-increasing (n = 671, 36.8%), moderate-increasing (n = 940, 51.5%), and high-increasing (n = 214, 11.7%); male participants exhibited a steeper increase in BMI than females. The uACR was increased linearly from the low- to high-increasing group. A total of 201 individuals developed albuminuria, with an incidence of 11.0%. Compared with the low-increasing group, the odds ratio (OR) of albuminuria in middle age was 2.13(95% confidence interval [CI]: 1.26 to 3.61) for the high-increasing group after full adjustment for age, sex, smoking, alcohol consumption, marital status, systolic blood pressure, diabetes, and hyperlipidemia. The unadjusted ORs of the high-increasing BMI group were 5.08 (2.76-9.37) for males and 3.45 (1.78-6.69) for females, and the association remained significant in males in the fully adjusted models. Interpretation: Higher BMI trajectories are associated with higher uACR and an increased risk of albuminuria in middle age, especially in males. Identifying long-term BMI trajectories from an early age may assist in predicting the risk of renal diseases and cardiovascular disease later in life. Funding: This work was supported by the National Natural Science Foundation of China (81600327, 82070437, 81870319, 82070549, and 82170437), Natural Science Basic Research Program of Shaanxi Province (2021JM-257 and 2021JM-588), Institutional Foundation of the First Affiliated Hospital of Xi'an Jiaotong University (2019QN-06 and 2021ZXY-14), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (XJTU1AF-CRF-2019-004, XJTU1AF2021CRF-021, and XJTU1AFCRF-2017-021), Research Incubation Fund of Xi'an People's Hospital (FZ-61), Grants from the Major Chronic Non-communicable Disease Prevention and Control Research Key Project of the Ministry of Science and Technology of China (2017YFC1307604 and 2016YFC1300104).

Associations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study.

BACKGROUND: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. METHODS: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g. RESULTS: During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SDSBP , ARVSBP , SDDBP , ARVDBP , SDMAP , ARVMAP , and ARVPP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. CONCLUSIONS: Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life.

Associations of genetic variations in NEDD4L with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.

Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), a member of the E3 ubiquitin-protein ligases, encoded by NEDD4L gene, was found to be involved in in salt sensitivity by regulating sodium reabsorption in salt-sensitive rats. The authors aimed to explore the associations of NEDD4L genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in Chinese adults. Participants from 124 families in Northern China in the Baoji Salt-Sensitive Study Cohort in 2004, who received the chronic salt intake intervention, including a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day), were analyzed. Besides, the development of hypertension over 14 years was evaluated. NEDD4L single nucleotide polymorphism (SNP) rs74408486 was shown to be significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet, while SNPs rs292449 and rs2288775 were significantly associated with pulse pressure (PP) response to high-salt diet. In addition, SNP rs4149605, rs73450471, and rs482805 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP at 14 years of follow-up. SNP rs292449 was significantly associated with hypertension incidence over the 14-year follow-up. Finally, this gene-based analysis found that NEDD4L was significantly associated with longitudinal BP changes and the incidence of hypertension over the 14-year follow-up. This study indicated that gene polymorphism in NEDD4L serve an important function in salt sensitivity, longitudinal BP change and development of hypertension in the Chinese population.