Global profiling of transcriptome, proteome and 2-hydroxyisobutyrylome in radioresistant lung adenocarcinoma cell.

Radioresistance contributes to metastasis and recurrence in non-small cell lung cancer (NSCLC) patients. However, the underlying mechanism remains unclear. To provide novel clues, a complete multi-omics map of a radioresistant cancer cell line has been profiled. In this article, a lung adenocarcinoma cell line, radioresistant A549 (RA549), was generated by exposure to a series of irradiation. Subsequently, we adopted transcriptome, quantitative proteome and lysine 2-hydroxyisobutyrylome to construct a differential profile on the transcriptional to post-tanslational levels on A549 and RA549 cell lines, respectively. Our analysis revealed 920 significantly differentially expressed genes and 699 proteins. Furthermore, 2-hydroxyisobutyrylome identified 30,089 Khib modified sites on 4635 proteins, indicating that Khib modifications play vital role in regulating NSCLC radioresistance. Multi-omics combined analysis identified 19 significantly differentially expressed genes/proteins in total. Meanwhile, we found that EGFR, a well-known lung cancer-related receptor, was upregulated at both the protein and Khib modification levels in RA549. Further gain/loss of function experiments showed that Khib modified EGFR level positively correlates with NSCLC cell radioresistance. Taken together, our findings report that Khib-modified proteins enhanced resistance to radiation and represent promising therapeutic targets.

Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P < 6 × 10 - 10 after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

Overview of mechanisms and novel therapies on rheumatoid arthritis from a cellular perspective.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of joints in response to autoimmune disorders. Once triggered, many factors were involved in the development of RA, including both cellular factors like osteoclasts, synovial fibroblasts, T cells, B cells, and soluble factors like interleukin-1 (IL-1), IL-6, IL-17 and tumor necrosis factor-α (TNF-α), etc. The complex interplay of those factors results in such pathological abnormality as synovial hyperplasia, bone injury and multi-joint inflammation. To treat this chronic life-affecting disease, the primary drugs used in easing the patient's symptoms are disease-modifying antirheumatic drugs (DMARDs). However, these traditional drugs could cause serious side effects, such as high blood pressure and stomach ulcers. Interestingly, recent discoveries on the pathogenesis of RA have led to various new kinds of drugs or therapeutic strategies. Therefore, we present a timely review of the latest development in this field, focusing on the cellular aspects of RA pathogenesis and new therapeutic methods in clinical application. Hopefully it can provide translational guide to the pre-clinical research and treatment for the autoimmune joint disease.

Transcriptome analysis and genome-wide identification of the dehydration-responsive element binding gene family in jackfruit under cold stress.

BACKGROUND: Jackfruit (Artocarpus heterophyllus Lam.) is the world's largest and heaviest fruit and adapts to hot, humid tropical climates. Low-temperature injury in winter is a primary abiotic stress, which affects jackfruit growth and development. Therefore, breeding cold-resistant varieties and identifying the vital genes in the process of cold resistance are essential. The dehydration-responsive element binding (DREB) gene family is among the subfamily of the APETALA2/ethylene response factor transcription factor family and is significant in plant abiotic stress responses. METHODS: In this study, a comparative analysis of the cold resistance property of 'GuangXi' ('GX') and 'Thailand' ('THA') jackfruit strains with different cold resistance characteristics was performed through chlorophyll fluorescence and transcriptome sequencing. RESULTS: We found that differentially expressed genes (DEGs) are significantly enriched in the metabolic processes. Here, 93 DREB genes were identified in the jackfruit genome, and phylogenetic analysis was used to classify them into seven groups. Gene structure, conserved motifs, chromosomal location, and homologous relationships were used to analyze the structural characteristics of the DREB family. Transcriptomics indicated that most of the AhDREB genes exhibited down-regulated expression in 'THA.' The DEGs AhDREB12, AhDREB21, AhDREB29, and AhDREB34 were selected for quantitative real-time PCR, and the results showed that these genes also had down-regulated expression in 'THA.' CONCLUSIONS: The above results suggest the significance of the DREB family in improving the cold resistance property of 'GX.'

Proteomic Assessment of the Risk of Secondary Cardiovascular Events among Individuals with CKD.

BACKGROUND: Cardiovascular risk models have been developed primarily for incident events. Well-performing models are lacking to predict secondary cardiovascular events among people with a history of coronary heart disease, stroke, or heart failure who also have chronic kidney disease (CKD). We sought to develop a proteomics-based risk score for cardiovascular events in individuals with CKD and a history of cardiovascular disease. METHODS: We measured 4638 plasma proteins among 1067 participants from the Chronic Renal Insufficiency Cohort (CRIC) and 536 individuals from the Atherosclerosis Risk in Communities Cohort (ARIC). All had non-dialysis-dependent CKD and coronary heart disease, heart failure, or stroke at study baseline. A proteomic risk model for secondary cardiovascular events was derived by elastic net regression in CRIC, validated in ARIC, and compared to clinical models. Biologic mechanisms of secondary events were characterized through proteomic pathway analysis. RESULTS: A 16-protein risk model was superior to the Framingham risk score for secondary events, including a modified score that included estimated glomerular filtration rate (eGFR). In CRIC, the annualized area under the receiver operating characteristic (AUC) within 1 to 5 years ranged between 0.77 and 0.80 for the protein model and 0.57 and 0.72 for the clinical models. These findings were replicated in the ARIC validation cohort. Biologic pathway analysis identified pathways and proteins for cardiac remodeling and fibrosis, vascular disease, and thrombosis. CONCLUSIONS: The proteomic risk model for secondary cardiovascular events outperformed clinical models based on traditional risk factors and eGFR.

Identifying Who Benefits the Most from a Community Health Worker-Led Multicomponent Intervention for Hypertension.

Background: Uncontrolled hypertension is a major public health challenge in low- and middle-income countries. The Hypertension Control Program in Argentina (HCPIA) showed that a community health worker-led multicomponent intervention was effective for blood pressure (BP) reduction in resource-limited settings, but whether the intervention was equally effective across participant subgroups is unknown. Objective: To identify participants who benefit the most from the HCPIA BP control intervention. Methods: This secondary analysis used data from HCPIA, a successful 18-month cluster-randomized trial in 18 health centers with 1,432 low-income hypertensive patients in Argentina. Fifteen baseline characteristics were used to define subgroups. The proportion of controlled BP (<140/90 mmHg) was estimated using generalized linear mixed models with arm-by-subgroup interaction terms. The distribution of trial BP response among intervention patient subgroups was assessed. Results: Participants were 53.0% female, a mean age of 56 years, and 17.4% controlled BP at baseline. After the intervention, 72.9% of intervention and 52.2% of control participants had controlled BP. The intervention was more effective in physically inactive patients (OR = 2.76, 95% CI: 1.82 and 4.21; p for interaction = 0.04), moderately active patients (OR = 3.08, 95% CI: 1.90 and 4.99; p for interaction = 0.03), and those with uncontrolled BP at baseline (OR = 2.77, 95% CI: 2.15 and 3.57; p for interaction = 0.05). Among intervention participants, 20.2% had no BP response (BP change < -4 mmHg), 41.3% had a moderate BP response (BP change: -4 mmHg to -24 mmHg), and 38.5% had a high BP response (BP change > -24 mmHg). Women (p=0.01), those who were physically inactive (p=0.03), and those not taking antihypertensive medications at baseline (p=0.001) had the greatest BP response. Conclusion: The effect of the intervention was consistent across many subgroups with some key groups showing a particularly strong intervention effect. These findings could be useful for planning future hypertension control programs in low- and middle-income countries.

A ratiometric fluorescent probe combined with smartphone technology based on cellulose for the detection of hypochlorous acid.

Hypochloric acid (HClO) is a reactive oxygen species (ROS). ROS is an important component that has antibacterial effects on the biological immune defense system. Therefore, the detection of HClO has become an unavoidable issue. This paper reports a cellulose-based fluorescent probe. Naphthalimide serves as the fluorescent group, and the methylthio group serves as the recognition site. The principle is that HClO can oxidise the methyl sulphide group to a sulphoxide. Under a 365 nm UV lamp, this ratiometric fluorescent probe emits a bright yellow green fluorescence, which turns blue after adding HClO. This probe uses more environmentally friendly and sustainable biomass resources, and has significant fluorescence characteristics compared to most reported probes. Its detection limit (LOD) is as low as 4.34 µM. The equilibrium constant K = 3.54 × 102 M-1 for the probe plus HClO. The response time is 30 s, and it has good specificity recognition and anti-interference ability. In addition, the probe has been successfully prepared into a fluorescent film, providing potential applications for the convenient detection of HClO. Finally, the probe will be combined with smartphone technology as a portable signal processing device to further achieve visual detection of HClO.

Antiphospholipid Antibodies Modify the Prognostic Value of Baseline Platelet Count for Clinical Outcomes After Ischemic Stroke.

BACKGROUND: Antiphospholipid antibodies (aPLs) have been reported to be involved in platelet-mediated thrombosis and inflammation, but the impact on the prognosis of ischemic stroke remains unclear. We aimed to examine whether the association between baseline platelet count (PLT) and long-term clinical outcomes within 2 years after ischemic stroke onset is modulated by aPLs. METHODS AND RESULTS: A total of 2938 patients with ischemic stroke were included in this prospective cohort study. Cox proportional hazards regression models were used to assess the association between the baseline PLT stratified by aPLs status and 2-year clinical outcomes after stroke onset, and an interaction effect between PLT and aPLs on clinical outcomes was tested by likelihood ratio test. There was a significant interaction effect of aPLs and PLT on recurrent stroke (Pinteraction=0.002) and cardiovascular events (Pinteraction=0.001) within 2 years after stroke onset. After multivariate adjustment, high PLT was associated with increased risks of recurrent stroke (hazard ratio [HR], 2.78 [95% CI, 1.03-7.45]; Ptrend=0.039) and cardiovascular events (HR, 2.58 [95% CI, 1.12-5.90]; Ptrend=0.024) when 2 extreme tertiles were compared among patients with aPL positive, but not among those with aPL negative. CONCLUSIONS: The aPLs had a modifying effect on the association between PLT and clinical outcomes within 2 years after ischemic stroke onset. Increased PLT was associated with recurrent stroke and cardiovascular events after ischemic stroke onset among patients with aPL positive, but not in those with aPL negative.

Serum Soluble Corin and Long-Term Clinical Outcomes After Acute Ischemic Stroke.

BACKGROUND: Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long-term clinical outcomes after acute ischemic stroke. METHODS AND RESULTS: We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all-cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log-corin was associated with a 21% (95% CI, 11-30), 16% (95% CI, 6-26), and 12% (95% CI, 3-21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all-cause mortality and cardiovascular events, as shown by C-statistics (all P<0.05). CONCLUSIONS: Serum soluble corin was associated with decreased risks of long-term clinical outcomes, and may be a promising prognostic biomarker for risk stratification in patients with acute ischemic stroke.

Sustainable phosphorescent oscillators based on photochemical deoxygenation in convections.

Upon constant photo-excitation, the phosphorescence intensities of long-lived triplet emitters dissolved in sulfoxide solvents under air exhibit periodic oscillations with regulatable frequencies and amplitudes, which is attributed to the interplay between photochemical deoxygenation and Rayleigh-Bénard convections.

The effectiveness of targeted therapy for recurrence or metastasis adenoid cystic carcinoma: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Several clinical studies have demonstrated the potential of molecular-targeted agents for the treatment of recurrent or metastatic adenoid cystic carcinoma (R/M ACC). However, there is currently no consensus regarding the efficacy of molecular-targeted agents for patients with R/M ACC. This study aimed to evaluate the therapeutic efficacy and safety of molecular-targeted agents in patients with R/M ACC and provide insights to guide clinical decision-making. MATERIALS AND METHODS: Five databases (PubMed, Embase, Cochrane, ProQuest, and Scopus) were searched based on the search strategy and selection criteria. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS), metastatic sites, and adverse events (AE). Pooled estimates were calculated using a random-effects meta-analysis. RESULTS: Finally, 28 studies, involving 849 patients, were included. The most common metastatic sites were the lungs, bones, liver, lymph nodes, and kidneys. The pooled ORR was 4.0% (95% CI, 0.7-8.8%), the pooled DCR was 80.5% (95% CI, 72.2%-87.7%). Compared with other-target drugs, multiple kinase inhibitors (MKIs) improved the ORR (pooled ORR for single-target drugs vs. MKIs: 5.9% vs. 0%). The combination of MKIs and immune checkpoint inhibitors (ICIs) had a significantly higher ORR (17.9% in the axitinib + avelumab group). The pooled median PFS and OS were 8.35 and 25.62 months, respectively. MKIs improved the median PFS compared to other-target drugs (9.43 months vs 5.06 months). In addition, the most common adverse events (AEs) were fatigue (51.6%), hypertension (44.2%), and nausea (40.0%), followed by hand-foot skin syndrome (36.8%), diarrhoea (34.4%), weight loss (34.2%), anorexia (31.8%), rash (31.7%), and headache (29.0%). CONCLUSION: The findings of this study suggest that MKIs have a better therapeutic efficacy than single-target drugs in patients with R/M ACC. Future studies are warranted to verify the synergistic role of the combination strategy of MKIs plus ICIs, given the limited number of studies on this topic conducted and published to date.

Optimal Antihypertensive Systolic Blood Pressure: A Systematic Review and Meta-Analysis.

BACKGROUND: Systolic blood pressure (SBP) lowering reduces major cardiovascular disease (CVD) and all-cause mortality. However, the optimal target for SBP lowering remains controversial. METHODS: We included trials with random allocation to an SBP <130 mm Hg treatment target and CVD as the primary outcome. Data were extracted from each study independently and in duplicate using a standardized protocol. Random-effects meta-analysis was used to obtain pooled hazard ratios (HRs) and 95% CIs for CVD and all-cause mortality comparing SBP <130 and ≥130 mm Hg treatment targets. A secondary analysis compared the same outcomes for randomization to an SBP target of <120 or <140 mm Hg. RESULTS: Seven trials, including 72 138 participants, met the eligibility criteria. Compared with an SBP target of ≥130 mm Hg, an SBP target of <130 mm Hg significantly reduced major CVD (HR, 0.78 [95% CI, 0.70-0.87]) and all-cause mortality (HR, 0.89 [95% CI, 0.79-0.99]). Compared with an SBP target of <140 mm Hg, an intensive SBP target of <120 mm Hg significantly reduced major CVD (HR, 0.82 [95% CI, 0.74-0.91]), but all-cause mortality was marginally insignificant (HR, 0.85 [95% CI, 0.71-1.01]). Adverse events were significantly more likely in the intensive SBP target groups, but the absolute risks were low. CONCLUSIONS: This study suggests targeting an SBP <130 mm Hg significantly reduces the risks of major CVD and all-cause mortality. The findings also support an SBP target of <120 mm Hg, based on a smaller number of trials. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023490693.

Tetradentate carbene-anilido boron complexes: highly fluorescent dyes with larger Stokes shifts than BODIPY analogues.

A new class of carbene-anilido boron complexes have been designed and synthesized. The complexes show intense fluorescence with large Stokes shift because of their charge-transfer excited states, different from typical BODIPY dyes. By using a chiral 1,1'-bi(2-naphthol) ligand, dyes exhibiting circularly polarized luminescence can also be facilely developed.

A two-step framework integrating lasso and Relaxed Lasso for resolving multidimensional collinearity in Chinese baijiu aging research.

The aging process is crucial for Chinese Baijiu production, significantly enhancing the spirit's flavor, aroma and quality. However, aging involves a complex interplay of numerous compounds, and the extensive duration required for aging leads to a scarcity of samples available for scientific research. These limitations pose a challenge in analyzing high-dimensional data with collinearity, complicating the understanding of the intricate chemical processes at play. In this article, a two-step framework was proposed that integrated Relaxed Lasso regression models with Lasso-selected predictors to address this issue. Baijiu samples subjected to various aging conditions were analyzed using direct GC-MS and HS-GC-MS, and the obtained data was processed by this approach. The results demonstrate significantly superior performance compared to other methods, including PLSR and Gradient Boosting. Analyses were also performed on a previously documented dataset, yielding enhanced results and underscoring the method's advantage in processing high dimensional data with multicollinearity. Moreover, this method proved effective in screening of potential indicative compounds, highlighting its utility in Baijiu aging research.

Bright green cellulose-based fluorescent probe toward Au3+ smartphone technology recognition and its visualization application.

In this study, a novel fluorescent probe, MAC-2, for the detection of Au3+ was designed and synthesised using cellulose as a carrier combined with benzothiazole derivatives. The structure of the probe was confirmed by SEM, XRD, FTIR, and 1H NMR, also the optical properties of the product were investigated. MAC-2 showed bright green fluorescence under a 365 nm UV lamp and exhibited significant quenching behaviour toward Au3+. MAC-2 utilises more sustainable biomass resources, featuring green and biodegradable characteristics that meet environmental requirements. Compared with most reported probes, it exhibits notable fluorescence properties. The limit of detection (LOD) is as low as 0.057 µM, and the response time is 1 min. It also demonstrates good specific recognition and anti-interference abilities. In addition, a smartphone was used as a portable signal processing device to achieve rapid detection of Au3+ concentration. Meanwhile, MAC-2 was successfully prepared as a fluorescent test strip, providing a potential application for the convenient detection of Au3+. The high sensitivity and selectivity exhibited by cellulose-based fluorescent probes in detecting Au3+ offer valuable insights and new ideas for the detection of other metal ions and biomolecules. These inspirations will help promote the continuous development of research and applications in related fields.

A rare case report of mucinous adenocarcinoma exacerbated by long-standing solitary rectal ulcer syndrome.

Background: Solitary rectal ulcer syndrome (SRUS) is a rare chronic rectal lesion with potential for malignant transformation, although cases of rapid progression to mucinous adenocarcinoma are infrequent. This case report highlights such an instance in a 29-year-old male patient, emphasizing the importance of vigilance among clinicians for detecting canceration in SRUS patients. Case Description: The patient presented with recurrent constipation and anal discomfort, initially diagnosed with SRUS based on colonoscopy and pathological examination. Despite long-term mesalazine treatment, symptoms persisted, and subsequent evaluation revealed the development of mucinous adenocarcinoma within a short period. Surgical resection, combined with adjuvant FOLFOX chemotherapy, effectively controlled cancer progression. Immunohistochemical analysis showed positive expression of MLH1(+), MSH2(+), MSH6(+), PMS2(+), and HER2(+), providing molecular insights into SRUS-associated mucinous adenocarcinoma. Conclusions: This case underscores the need for increased awareness among clinicians regarding the potential for cancerous transformation in SRUS patients. Early detection and intervention are crucial for improving outcomes in SRUS-associated malignancies. Furthermore, this case adds to existing literature by presenting a rare instance of SRUS progressing rapidly to mucinous adenocarcinoma, highlighting the significance of regular monitoring and timely intervention in such cases. Further research is warranted to elucidate underlying mechanisms and risk factors, guiding future clinical practice and treatment strategies.

Biological characteristics of flowers and examination of pollen viability at different developmental stages of Epimedium sagittatum (Sieb. et Zucc.) Maxim.

To gain a deeper understanding of the flowering pattern and reproductive characteristics of Epimedium sagittatum, to enrich the research on the flower development of E. sagittatum and its reproductive regulation, and to screen the methods suitable for the rapid detection of pollen viability of E. sagittatum and to promote its cross-breeding. The characteristics of its flower parts were observed, recorded and measured, and the pollen viability of E. sagittatumwas determined by five methods, including TTC staining, I2-KI staining, red ink staining, peroxidase method and in vitro germination method. The flowering process of E. sagittatum can be divided into five stages: calyx dehiscence, bract spathe, petal outgrowth, pollen dispersal, and pollination and withering. The results of I2-KI staining and peroxidase method were significantly higher than those of other methods; the in vitro germination method was intuitive and accurate, but the operation was complicated and time-consuming; the red ink staining method was easy to operate and had obvious staining effect, and the results were the closest to those of the in vitro germination method; and it was found that the pollen of E. sagittatum was not as effective as the in vitro germination method at the bud stamen stage, the flower stigma and the flower bud. It was also found that the pollen viability and germination rate of E. sagittatum pollen were higher in the three periods of bud spitting, petal adductor and pollen dispersal. Comparing the five methods, the red ink staining method was found to be a better method for the rapid detection of pollen viability; the best pollination periods of E. sagittatum were the bud stamen stage, petal adductor stage, and pollen dispersal stage of flowers at the peak of bloom. This study on the flowering and fruiting pattern of E. sagittatum, and the related mechanism of sexual reproduction, can be used as a reference for the next step of research on the breeding of E. sagittatum.

Mechanism of folium polygoni cuspidati in liver-yang-hyperactivity hypertension based on network pharmacology, molecular docking and experimental pharmacological validation.

ETHNOPHARMACOLOGICAL RELEVANCE: At present,the global form of hypertension is severe,and liver-yang-hyperactivity hypertension（GYSK hypertension）is the most common type of hypertension.Folium Polygoni Cuspidati（HZY）are mainly used in Yunnan, China,to treat dizziness, headache,and hypertension caused by GYSK,and the content of the active ingredients of HZY and its efficacy varies in different periods.However,the mechanism of action and the effect of harvesting period are not clear. AIM OF THE STUDY: The purpose of this research was to investigate the effect of HZY in April and September on GYSK hypertension. MATERIALS AND METHODS: The model of GYSK hypertension was established with aconite decoction and L-NAME,and the blood pressure,the symptoms of GYSK,the cardiac index and the pathological changes of aorta were observed,to study the effect of HZY in April and September on GYSK hypertension.The chemical composition of HZY was analysed by UPLC-QTOF-MS and its mechanism for the treatment of GYSK hypertension was predicted by network pharmacological studies and experimentally validated using serum metabolomics and Western blot techniques. RESULTS: April HZY and September HZY can significantly improve the GYSK symptoms of rats, inhibit the RAAS system, improve oxidative stress and regulate blood lipids so as to play a blood pressure lowering efficacy and have a protective effect on the vascular endothelial cells.UPLC-QTOF-MS yielded 29 components of HZY,and network pharmacology predicted that its mechanism may be related to Lipid and atherosclerosis,PI3K/Akt signaling pathway, MAPK signaling pathway and TNF signaling pathway,etc.Western Blot validation showed that HZY activated PI3K,p-Akt protein expression and inhibited p-erk,p-p38 and TNF-α protein expression.Serum metabolomics suggested that April HZY exerts its efficacy mainly by regulating amino acid metabolism and September HZY mainly by regulating lipid metabolism. CONCLUSIONS: In GYSK hypertensive rats treated for three weeks, both April HZY and September HZY could have antihypertensive effects,but the mechanisms of action were different and similar, both could regulate metabolite disorders of sugars, lipids,amino acids and peptides,and regulate blood pressure through the PI3K/Akt-eNOS and MAPK signalling pathways, with the difference that April HZY had stronger regulatory effects on the metabolism of amino acids.metabolism.

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown. METHODS: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean. RESULTS: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory. DISCUSSION: CHIP was associated with lower risks of impairment in attention and executive function among CKD patients. HIGHLIGHTS: Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

Early vs Delayed Antihypertensive Treatment in Acute Single Subcortical Infarction: A Secondary Analysis of the CATIS-2 Randomized Clinical Trial.

Importance: The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) suggests that early antihypertensive treatment did not reduce the risk of dependency or death in acute ischemic stroke (AIS), compared with delayed treatment. Single subcortical infarction (SSI) is an important stroke subtype, and the association of antihypertensive timing with clinical outcomes is unclear. Objective: To investigate the association of early vs delayed antihypertensive treatment with clinical outcomes in patients with SSI, stratified by the presence of parent artery disease (PAD) stenosis. Design, Setting, and Participants: This secondary analysis of the CATIS-2 randomized clinical trial included 106 hospitals in China between June 2018 and July 2022. In CATIS-2, patients with AIS within 24 to 48 hours of symptoms onset and elevated systolic blood pressure were eligible. Patients with SSI detected in diffusion-weighted imaging were included in the current post hoc subgroup analysis. Patients were grouped into (1) SSI with PAD stenosis and (2) SSI without PAD stenosis. Statistical analysis was performed from July 2023 to May 2024. Exposures: Early (immediate) vs delayed (starting on day 8) antihypertensive therapy. Main Outcome and Measure: Primary outcome was the combination of functional dependency or death (modified Rankin Scale score ≥3) at 90 days. Results: Among 997 patients with SSI in CATIS-2 (mean [SD] age, 62.4 [9.8] years; 612 [61.4%] men), 116 (11.6%) had SSI with PAD and 881 (88.4%) had SSI without PAD. There was no significant difference in the primary outcome between early and delayed antihypertensive treatment groups among all patients with SSI (8.8% vs 7.1%; OR, 1.25 [95% CI, 0.79-1.99]; P = .34). Among patients with SSI with PAD, early antihypertensive treatment was associated with increased risk of the primary outcome compared with delayed treatment (23.4% vs 7.7%; OR, 3.67 [95% CI, 1.14-11.86]; P = .03); this finding was not observed in patients with SSI without PAD (6.6% vs 7.1%; OR, 0.93 [95% CI, 0.55-1.57]; P = .77). Significant interaction with treatment and presence of PAD stenosis was detected for the primary outcome (P for interaction = .04). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, early antihypertensive treatment was associated with an increased risk of functional dependency or death at 90 days among patients with SSI and coexisting PAD stenosis, compared with delayed antihypertensive treatment. Further studies are warranted for individualized BP management in patients with SSI by the presence of PAD. Trial Registration: ClinicalTrials.gov Identifier: NCT03479554.