Diurnal variation of postoperative delirium in elderly patients undergoing esketamine anesthesia for elective noncardiac surgery: a randomized clinical trial.

BACKGROUND: Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients. METHODS: A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00-12:00) or afternoon (14:00-18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation. RESULTS: Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=-0.583, OR (95% CI) 0.558 (0.319-0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time. CONCLUSION: Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation.

Manganese exposure leads to depressive-like behavior through disruption of the Gln-Glu-GABA metabolic cycle.

There is a correlation between long-term manganese (Mn) exposure and the Parkinson's-like disease (PD), with depression as an early symptom of PD. However, the direct relationship between Mn exposure and depression, and the mechanisms involved, remain unclear. We found that Mn exposure led to depressive-like behavior and mild cognitive impairment in mice, with Mn primarily accumulating in the cornu ammonis 3 (CA3) area of the hippocampus. Mice displayed a reduction in neuronal dendritic spines and damage to astrocytes specifically in the CA3 area. Spatial metabolomics revealed that Mn downregulated glutamic acid decarboxylase 1 (GAD1) expression in astrocytes, disrupting the Glutamine-Glutamate-γ-aminobutyric acid (GlnGluGABA) metabolic cycle in the hippocampus, leading to neurotoxicity. We established an in vitro astrocyte Gad1 overexpression (OEX) model and found that the cultured medium from Gad1 OEX astrocytes reversed neuronal synaptic damage and the expression of gamma-aminobutyric acid (GABA) related receptors. Using the astrocyte Gad1 OEX mouse model, results showed that OEX of Gad1 ameliorated depressive-like behavior and cognitive dysfunction in mice. These findings provide new insight into the important role of GAD1 mediated GlnGluGABA metabolism disorder in Mn exposure induced depressive-like behavior. This study offers a novel sight to understanding abnormal emotional states following central nervous system damage induced by Mn exposure.

A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity.

Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (1-3) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex 3). In addition, a control compound (complex 4) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes 1-3 was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order 3 > 2 > 1, giving the IC50 values ranging from 2.874 ± 0.155 µM to 31.47 ± 0.29 µM against five cancer cell lines. Complex 4 showed less activity in comparison with complex 1-3. Notably, complexes 1-3 displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex 4 (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound 3 induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes 3 and 4 was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex 3 interacted with DNA in an intercalating mode, but the interaction mode of compound 4 with DNA was electrostatic interaction.

Hypertension status and its risk factors in highlanders living in Ganzi Tibetan Plateau: a cross-sectional study.

BACKGROUND: The updated status of hypertension and its risk factors are poorly evaluated in Tibetan highland areas. We initiated a large-scale cross-sectional survey to provide updated status of hypertension and its risk factors (especially salt intake) in the Ganzi Tibetan Plateau, China. METHODS: Stratified multistage random sampling was performed to obtain a representative sample of 4,036 adult residents from 4 counties in the Ganzi Tibetan area. The whole survey population was used to present the epidemiology and risk factors of hypertension. The participants with blood and urine biochemistry data were used to analyze the relationship between salt intake parameters and hypertension. RESULTS: Stratified multistage random sampling was performed to obtain a representative sample of 4,036 adult residents. The overall prevalence rate of hypertension was 33.5% (the age-adjusted prevalence rate was 28.9%). A total of 50.9% of the hypertensive patients knew their conditions; 30.1% of them received antihypertensive treatment; and 11.2% of them had their blood pressure controlled. Age, male sex, living altitude ≥ 3500 m, overweight and abdominal obesity were positively correlated with hypertension. In addition, the adjusted odds ratio (OR) for hypertension was 1.33 (95% CI: 1.01-1.74) for drinking tea with salt, and 1.51 (95% CI: 1.32-1.72) for per SD increase in the estimation of 24-hour urinary sodium excretion (e24hUSE). Furthermore, per 100mmol/day increase in e24hUSE was associated with elevation of blood pressure (+ 10.16, 95% CI: 8.45-11.87 mmHg for SBP; +3.83, 95% CI: 2.74-4.93 mmHg for DBP) in this population. CONCLUSIONS: Our survey suggests a heavy disease burden of hypertension in the Ganzi Tibetan Plateau. Age, male sex, altitude of residence ≥ 3500 m, overweight, abdominal obesity, and excessive salt intake (shown as drinking tea with adding salt and a higher level of e24hUSE) all increased the risk of hypertension in this highland area.

Rapid and on-site detection of bisulfite via a NIR fluorescent probe: A case study on the emission wavelength of probes with different quinolinium as electron-withdrawing groups.

The emission of venenous sulfur dioxide (SO2) and its derivatives from industrial applications such as coking, transportation and food processing has caused great concern about public health and environmental quality. Probes that enable sensitivity and specificity to detect SO2 derivatives play a crucial role in its regulations and finally mitigating its environmental and health impacts, but fluorescent probes that can accurately, rapidly and on-site detect SO2 derivatives in foodstuffs and environmental systems rarely reported. Herein, a near-infrared (NIR) fluorescent probe (ZTX) for the ratiometric response of bisulfite (HSO3-) was designed and synthesized by regulating the structure of high-performance HSO3- fluorescent probe SL previously reported by us based on structural analyses, theoretical calculations and related literature reports. The Michael addition reaction between the electronic-deficient C=C bond and HSO3- destroys ZTX's π-conjugation system and blocks its intramolecular charge transfer (ICT) process, resulting in a significant fading of the fuchsia solution and the bluish-purple fluorescence turned light blue fluorescence. Fluorescent imaging of HSO3- in live animals utilizing ZTX has been demonstrated. The quantitative analysis of HSO3- in food samples using ZTXvia a smartphone has been also successfully implemented. Simultaneously, the ZTX-based test strips were utilized to quantificationally determine HSO3- in environmental water samples by a smartphone. Consequently, probe ZTX could provide a new method to understand the physiopathological roles of HSO3-, evaluate food safety and monitor environment, and is promising for broad applications.

MCU inhibition protects against intestinal ischemia‒reperfusion by inhibiting Drp1-dependent mitochondrial fission.

Intestinal ischemia‒reperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemia‒reperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified. In this study, we generated an IIR model using C57BL/6 mice and Caco-2 cells and found increases in the calcium levels and MCU expression following IIR injury. The specific inhibition of MCU markedly attenuated IIR injury. Moreover, MCU knockdown alleviates mitochondrial dysfunction by reducing oxidative stress and apoptosis. Mechanistically, MCU knockdown substantially reduced the translocation of Drp1 and thus its binding to Fis1 receptors, resulting in decreased mitochondrial fission. Taken together, our findings demonstrated that MCU is a novel upstream regulator of Drp1 in ischemia‒reperfusion and represents a predictive and therapeutic target for IIR.

Ghrelin alleviates intestinal ischemia-reperfusion injury by activating the GHSR-1α/Sirt1/FOXO1 pathway.

Ischemia-reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia-reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 µg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.

Metalloproteins as risk factors for osteoarthritis: improving and understanding causal estimates using Mendelian randomization.

Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders and a primary cause of pain and disability among the elderly population. Research on the relationship between metalloproteins (MPs) and OA is limited, and causality remains unclear. Our objective is to utilize Mendelian randomization (MR) to explore the possible causal relationship between MPs and OA. The data on MPs were derived from a Genome-Wide Association Study (GWAS) analysis involving 3301 samples. The GWAS data for OA were obtained from an analysis involving 462,933 European individuals. In this study, a variety of two-sample Mendelian randomization methods (two-sample MR) to evaluate the causal effect of MPs on OA, including inverse variance weighted method (IVW), MR-Egger method, weighted median method (WM), simple mode, weight mode, and Wald ratio. The primary MR analysis using the IVW method reveals a significant negative correlation between Metallothionein-1F (MT-1F), zinc finger protein 134 (ZNF134), calcium/calmodulin-dependent protein kinase type 1D (CAMK1D), and EF-hand calcium-binding domain-containing protein 14 (EFCAB14) with the occurrence of osteoarthritis (OA) (p value < 0.05). However, no causal relationship was observed in the opposite direction between these MPs and OA. Notably, even in combined models accounting for confounding factors, the negative association between these four MPs and OA remained significant. Sensitivity analysis demonstrated no evidence of horizontal pleiotropy or heterogeneity, and leave-one-out analysis confirmed the robustness of the results. In this study, we have established a conspicuous association between four distinct MPs and OA. This discovery augments our understanding of potential avenues for the diagnosis and treatment of this condition. Key Points • The MR method was employed to assess the relationship between MPs and OA. • A total of four types of MPs have demonstrated inhibitory effects on the occurrence of OA.

Low-level PM2.5 induces the occurrence of early pulmonary injury by regulating circ_0092363.

The significant correlation between particulate matter with aerodynamic diameters of ≤ 2.5 µm (PM2.5) and the high morbidity and mortality of respiratory diseases has become the consensus of the research. Epidemiological studies have clearly pointed out that there is no safe concentration of PM2.5, and mechanism studies have also shown that exposure to PM2.5 will first cause pulmonary inflammation. Therefore, the purpose of this study is to explore the mechanism of early lung injury induced by low-level PM2.5 from the perspective of epigenetics. Based on the previous results of population samples, combined with an in vitro/vivo exposure model of PM2.5, it was found that low-level PM2.5 promoted the transport of circ_0092363 from intracellular to extracellular spaces. The decreased expression of intracellular circ_0092363 resulted in reduced absorption of miR-31-5p, leading to inhibition of Rho associated coiled-coil containing protein kinase 1 (ROCK1) and the subsequent abnormal expression of tight junction proteins such as Zonula occludens protein 1 (ZO-1) and Claudin-1, ultimately inducing the occurrence of early pulmonary injury. Furthermore, this study innovatively introduced organoid technology and conducted a preliminary exploration for a study of the relationship among environmental exposure genomics, epigenetics and disease genomics in organoids. The role of circ_0092363 in early pulmonary injury induced by low-level PM2.5 was elucidated, and its value as a potential diagnostic biomarker was confirmed.

In situ profiling reveals spatially metabolic injury in the initiation of polystyrene nanoplastic-derived intestinal epithelial injury in mice.

Despite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury.

BMS-794833 reduces anlotinib resistance in osteosarcoma by targeting the VEGFR/Ras/CDK2 pathway.

Background: Osteosarcoma, a tumor that originates from bone cells, has a poor prognosis and a high degree of malignancy. Anlotinib, a small-molecule multi-target tyrosine kinase inhibitor (TKI), is the first-line drug in treating osteosarcoma, especially in late-stage osteosarcoma. However, patients often develop resistance after using anlotinib for a certain period, which poses a challenge to its further clinical application. Recently, several TKIs, for instance regorafenib and cabozantinib, have showed clinical interest in treating osteosarcoma and target both vascular endothelial growth factor receptor (VEGFR) and mesenchymal epithelial transition factor (c-MET). Therefore, the identification of new TKI warrants further investigation. Methods: We performed CCK8 aasays to confirm that BMS-794833 sensitization osteosarcoma cells to anlotinib. Bioinformatics analysis and rescue experiments showed that the reduce of resistance were dependent on the VEGFR/Ras/CDK2 pathway. Cell line based xenograft model were used to demonstrate that BMS-794833 and anlotinib could synergistically treat OS. Results: Here, we found that BMS-794833 reduced anlotinib resistance in osteosarcoma by targeting the VEGFR/Ras/CDK2 pathway. CCK8 assay showed that BMS-794833 significantly improved the resistance of osteosarcoma cells to anlotinib. The results of rescue experiments showed that the regulatory effects of BMS-794833 on the proliferation and drug resistance of osteosarcoma cells were dependent on the VEGFR/Ras/CDK2 pathway. In addition, BMS-794833 affected the resistance of osteosarcoma cells to anlotinib through epithelial-mesenchymal transition (EMT) and apoptosis pathways. More importantly, BMS-794833 and anlotinib exerted synergistic therapeutic effects against osteosarcoma in vivo. Conclusion: Altogether, this study reveals a new (VEGFR)-targeting drug that can be combined with anlotinib for the treatment of osteosarcoma, which provides an important theoretical basis for overcoming anlotinib resistance.

PHE-SICH-CT-IDS: A benchmark CT image dataset for evaluation semantic segmentation, object detection and radiomic feature extraction of perihematomal edema in spontaneous intracerebral hemorrhage.

BACKGROUND AND OBJECTIVE: Intracerebral hemorrhage is one of the diseases with the highest mortality and poorest prognosis worldwide. Spontaneous intracerebral hemorrhage (SICH) typically presents acutely, prompt and expedited radiological examination is crucial for diagnosis, localization, and quantification of the hemorrhage. Early detection and accurate segmentation of perihematomal edema (PHE) play a critical role in guiding appropriate clinical intervention and enhancing patient prognosis. However, the progress and assessment of computer-aided diagnostic methods for PHE segmentation and detection face challenges due to the scarcity of publicly accessible brain CT image datasets. METHODS: This study establishes a publicly available CT dataset named PHE-SICH-CT-IDS for perihematomal edema in spontaneous intracerebral hemorrhage. The dataset comprises 120 brain CT scans and 7,022 CT images, along with corresponding medical information of the patients. To demonstrate its effectiveness, classical algorithms for semantic segmentation, object detection, and radiomic feature extraction are evaluated. The experimental results confirm the suitability of PHE-SICH-CT-IDS for assessing the performance of segmentation, detection and radiomic feature extraction methods. RESULTS: This study conducts numerous experiments using classical machine learning and deep learning methods, demonstrating the differences in various segmentation and detection methods on the PHE-SICH-CT-IDS. The highest precision achieved in semantic segmentation is 76.31%, while object detection attains a maximum precision of 97.62%. The experimental results on radiomic feature extraction and analysis prove the suitability of PHE-SICH-CT-IDS for evaluating image features and highlight the predictive value of these features for the prognosis of SICH patients. CONCLUSION: To the best of our knowledge, this is the first publicly available dataset for PHE in SICH, comprising various data formats suitable for applications across diverse medical scenarios. We believe that PHE-SICH-CT-IDS will allure researchers to explore novel algorithms, providing valuable support for clinicians and patients in the clinical setting. PHE-SICH-CT-IDS is freely published for non-commercial purpose at https://figshare.com/articles/dataset/PHE-SICH-CT-IDS/23957937.

Sestrin2 reduces ferroptosis via the Keap1/Nrf2 signaling pathway after intestinal ischemia-reperfusion.

Sestrins are metabolic regulators that respond to stress by reducing the levels of reactive oxygen species (ROS) and inhibiting the activity of target of rapamycin complex 1 (mTORC1). Previous research has demonstrated that Sestrin2 mitigates ischemia-reperfusion (IR) injury in the heart, liver, and kidneys. However, its specific role in intestinal ischemia-reperfusion (IIR) injury remains unclear. To elucidate the role of Sestrin2 in IIR injury, we conducted an experimental study using a C57BL/6J mouse model of IIR. We noticed an increase in the levels of Sestrin2 expression and indicators associated with ferroptosis. Our study revealed that manipulating Sestrin2 expression in Caco-2 cells through overexpression or knockdown resulted in a corresponding decrease or increase, respectively, in ferroptosis levels. Furthermore, our investigation revealed that Sestrin2 alleviated ferroptosis caused by IIR injury through the activation of the Keap1/Nrf2 signal pathway. This finding highlights the potential of Sestrin2 as a therapeutic target for alleviating IIR injury. These findings indicated that the modulation of Sestrin2 could be a promising strategy for managing prolonged IIR injury.

Mic19 depletion impairs endoplasmic reticulum-mitochondrial contacts and mitochondrial lipid metabolism and triggers liver disease.

Endoplasmic reticulum (ER)-mitochondria contacts are critical for the regulation of lipid transport, synthesis, and metabolism. However, the molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, we show that Mic19, a key subunit of MICOS (mitochondrial contact site and cristae organizing system) complex, regulates ER-mitochondria contacts by the EMC2-SLC25A46-Mic19 axis. Mic19 liver specific knockout (LKO) leads to the reduction of ER-mitochondrial contacts, mitochondrial lipid metabolism disorder, disorganization of mitochondrial cristae and mitochondrial unfolded protein stress response in mouse hepatocytes, impairing liver mitochondrial fatty acid ß-oxidation and lipid metabolism, which may spontaneously trigger nonalcoholic steatohepatitis (NASH) and liver fibrosis in mice. Whereas, the re-expression of Mic19 in Mic19 LKO hepatocytes blocks the development of liver disease in mice. In addition, Mic19 overexpression suppresses MCD-induced fatty liver disease. Thus, our findings uncover the EMC2-SLC25A46-Mic19 axis as a pathway regulating ER-mitochondria contacts, and reveal that impairment of ER-mitochondria contacts may be a mechanism associated with the development of NASH and liver fibrosis.

A near-infrared fluorescent probe for rapid and on-site detection of sulfur dioxide derivative in biological, food and environmental systems.

Emission of toxic gaseous sulfur dioxide (SO2) and its derivative bisulfite (HSO3-) from various industrial applications, like food processing, transportation, and the coking process, has raised substantial concerns regarding environmental quality and public health. The probes for specific and sensitive detection of SO2 derivatives plays an essential role in their regulation, and ultimately mitigating their environmental and health implications, but the one that can detect SO2 derivatives onsite by end users remains limited. Herein, we report a new near-infrared fluorescence probe (SL) for rapid and onsite detection of SO2 derivative, HSO3- in industrial wastewater, food samples and for sensing its interaction with biological organisms. The SL is developed through coupling of quinolinium and coumarin moiety through an electron deficit CC bond that can specifically react with HSO3- via a Michael addition. By recording the blue shift of absorption and emission spectra, SL can sensitively detect HSO3- (limit of detection, 38 nM) in aqueous solution within 40 s SL is biocompatible, can be used for evaluating toxicity of SO2 derivatives in living organisms. The preparation of SL-stained test paper allows the colorimetric/fluorometric analysis for quantification of HSO3- onsite in food, river and coking wastewater samples using a smartphone. The successful development of SL not only provides a new tool to investigate HSO3- in biological, food and environmental systems, but also potentially promotes the application of fluorescence technique for rapid and onsite analysis of real-world samples by end users.

L.acidophilus participates in intestinal inflammation induced by PM2.5 through affecting the Treg/Th17 balance.

Particulate matter with aerodynamic diameters of ≤2.5 µm (PM2.5) is associated with multiple organ damage, among which the influence of PM2.5 on the gastrointestinal system has been a recent focus of attention. In this study, four different types of PM2.5 exposure models are established to determine the occurrence of PM2.5 induced intestinal inflammation. In view of the abnormal expression of lymphocytes detected in the model and the well-known fact that the intestine is the largest immune organ, we focused on the intestinal immune system. A combined regulatory T cell (Treg) transplantation experiment demonstrated that PM2.5 induced intestinal inflammation by affecting the imbalance of regulatory T cell/T helper cell 17 (Treg/Th17). Since the intestine has the highest microbial content, and the results of the 16S rDNA third-generation sequencing analysis further revealed that the abundance of Lactobacillus_acidophilus (L.acidophilus) decreased significantly after PM2.5 exposure. The following mechanism study confirmed that L.acidophilus participated in an imbalance of Treg/Th17. Moreover, L.acidophilus supplementation successfully alleviated intestinal inflammation by regulated regulating the balance of Treg/Th17 under the background of PM2.5 exposure. Hence, this is a potential method to protect against intestinal inflammation induced by PM2.5.

Association between hemoglobin concentration and hypertension risk in native Tibetans at high altitude.

Previous studies examining the association between hemoglobin concentration and hypertension have yielded inconsistent results. There is still a lack of evidence regarding the association between hemoglobin concentration and hypertension risk in native Tibetans at high altitude. We performed this cross-sectional study in Luhuo County of Ganzi Tibetan Autonomous Prefecture (average altitude of 3500 m). In this study, we enrolled 1547 native Tibetans. The association between hemoglobin concentration and hypertension risk was examined by multivariate binary logistic regression and smooth curve fitting. Native Tibetans with hypertension had significantly higher hemoglobin concentrations than those without hypertension (165.9 ± 21.5 g/L vs. 157.7 ± 19.2 g/L, P < 0.001). An increase in hemoglobin concentration of 1 g/L was associated with hypertension (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.02) after confounder adjustment. The highest hemoglobin concentration group (exceeding 173 g/L) was associated with an increased hypertension risk compared with the bottom quartile of hemoglobin concentration (OR 2.39, 95% CI 1.48-3.85). Hemoglobin concentration (per 1 g/L change) exceeding 176 g/L was significantly associated with an increased hypertension risk (OR 1.04, 95% CI 1.03-1.06). Additionally, high-altitude polycythemia significantly increased the hypertension risk compared with a normal hemoglobin concentration (OR 2.92, 95% CI 1.25-6.86). A similar result was observed for mild polycythemia (OR 1.74, 95% CI 1.29-2.34). In conclusion, hemoglobin concentration was associated with hypertension risk in native Tibetans. When the hemoglobin concentration exceeded a certain value (approximately 176 g/L), the risk of hypertension was significantly increased.

The effects of Olmesartan/amlodipine administered in the Morning or At Night on nocturnal blood pressure reduction in Chinese patients with mild-moderate essential hypertension (OMAN Trial): study protocol for a prospective, multicenter, randomized, open-label clinical trial {1}.

INTRODUCTION: Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30-60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension. METHODS AND ANALYSIS: This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6-10 am) or a bedtime (6-10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12. DISCUSSION: Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice. TRIAL REGISTRATION: ChiCTR2200059719. Registered on 10 May 2022 ( http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4 ) {2a,2b}.