The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

OBJECTIVE To study the clinical efficacy of Professor Li Bingmao's Tongfu Xiere Quyu Shuli Prescription in the treatment of patients with functional dyspepsia(FD)of spleen and stomach damp-heat and qi stagnation and blood stasis type.METH-ODS A total of 206 patients with functional dyspepsia of spleen and stomach damp-heat and qi stagnation and blood stasis type diag-nosed by Hengshui People's Hospital were included in the study and randomly divided into a study group and a control group with 103 cases in each group.During the treatment,3 cases dropped out in each group.The control group adopted the conventional Western medicine treatment plan for functional dyspepsia(mosapride+rabeprazole),and the study group took Tongfu Xiere Quyu Shuli Pre-scription on the basis of the treatment of the control group.The treatment course of both groups was 4 weeks.The traditional Chinese medicine(TCM)syndrome scores,psychological status[self-rating anxiety scale(SAS),self-rating depression scale(SDS),and quality of life[Nepean dyspepsia life quality index(NDLQI)of the two groups of patients before and after treatment were observed and the clinical efficacy was evaluated;serum motilin(MTL),ghrelin,gastrin(GAS),corticotropin-releasing hormone(CRH)and pep-sinogen(PG Ⅰ,PG Ⅱ)were measured by enzyme-linked immunosorbent assay;changes in gastric motility indexes were analyzed by electrogastrogram analyzer;changes in intestinal flora were detected by instillation method.The occurrence of adverse reactions in the two groups of patients was monitored during treatment.RESULTS After treatment,the TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score in the study group was lower than that in the control group(P<0.01).The total effective rate of the study group was significantly higher than that in the control group(P<0.01).After treatment,the expression levels of MTL,Ghrelin,GAS,PG Ⅰ and PG Ⅱ in the two groups increased,and CRH decreased,and the improvement degree of the study group was better than that of the control group(P<0.01).After treatment,the main frequency and slow wave percentage of the electrogastrogram increased in the two groups,and the study group was better than that of the control group(P<0.01).After treat-ment,the number of bifidobacteria and lactobacilli in the two groups increased,and the number in the study group was greater than that in the control group,while the number of enterobacteria,enterococci and yeast decreased,and the number in the study group was less than that in the control group(P<0.01).There was no significant difference in adverse reactions between the two groups(P>0.05).CONCLUSION Tongfu Xiere Quyu Shuli Prescription is effective in the treatment of FD patients with spleen and stomach damp-heat syndrome,and can improve FD clinical symptoms,quality of life,anxiety and depression symptoms,regulate gastrointesti-nal hormone expression levels,gastric motility and intestinal flora expression,and does not increase adverse reactions,and is safe and reliable.

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

Objective:To investigate the prognoses of patients with medial medullary infarction (MMI) or lateral medullary infarction (LMI) and their influencing factors.Methods:A retrospective analysis was performed; 489 patients with acute medullary infarction admitted to Department of Neurology, Tianjin Huanhu Hospital from January 2017 to January 2024 were enrolled. Among them, 186 patients had MMI, which was divided into isolated MMI group ( n=126) and group of MMI with other infarcts ( n=60); 303 patients had LMI, which was divided into isolated LMI group ( n=176) and group of LMI with other infarcts ( n=127). Prognosis 90 days after onset was assessed by modified Rankin Scale (mRS, scores of 3-6 as poor prognosis). Clinical data, prognosis and mortality 90 days after onset, early neurological deterioration, respiratory failure, and complications were compared between isolated MMI group and group of MMI with other infarcts and between isolated LMI group and group of LMI with other infarcts. Univariate and multivariate Logistic regression analyses were used to identify the independent influencing factors for poor prognosis 90 days after onset in patients with MMI or LMI. Results:(1) Compared with isolated MMI group, group of MMI with other infarcts had significantly lower rates of alcohol history and sensory symptoms but higher rates of Horner's syndrome, dysphagia, dysarthria, and facial palsy ( P<0.05). Compared with isolated LMI group, group of LMI with other infarcts had significantly lower rates of sensory symptoms but higher rates of dizzy and dysarthria, and statistically different Trial of ORG 10172 in Acute Stroke Treatment types ( P<0.05). (2) The poor prognosis rate 90 days after onset in patients with MMI was significantly higher than that in patients with LMI (31.8% vs. 18.8%, P<0.05). Compared with isolated MMI group, group of MMI with other infarcts had significantly higher rates of respiratory failure, urinary retention, and pulmonary infection ( P<0.05). Compared with isolated LMI group, group of LMI with other infarcts had significantly higher rates of poor prognosis 90 days after onset, mortality 90 days after onset, early neurological deterioration, respiratory failure, stress ulcers, and pulmonary infection ( P<0.05). (3) Multivariate Logistic regression analysis revealed that dyskinesia ( OR=10.522, 95% CI: 1.246-88.853, P=0.031) and vertical multi-level involvement ( OR=4.585, 95% CI: 1.405-14.962, P=0.012) were independent influencing factors for poor prognosis in isolated MMI patients 90 days after onset; age ( OR=1.089, 95% CI: 1.017-1.166, P=0.015), vertical multi-level involvement ( OR=9.429, 95% CI: 1.625-54.502, P=0.012) were independent influencing factors for poor prognosis in MMI patients with other infarcts 90 days after onset; age ( OR=1.069, 95% CI: 1.006-1.136, P=0.031) and vertical multi-level involvement ( OR=7.125, 95% CI: 2.243-22.636, P<0.001) were independent influencing factors for poor prognosis in isolated LMI patients 90 days after onset; diabetes ( OR=2.807, 95% CI: 1.056-7.461, P=0.038), dysphagia ( OR=6.821, 95% CI: 1.978-23.518, P=0.002), and temporal-occipital infarcts ( OR=3.419, 95% CI: 1.133-10.302, P=0.029) were independent influencing factors for poor prognosis in LMI patients with other infarcts. Conclusion:Patients with LMI had better prognosis compared with patients with MMI; however, LMI patients with other infarcts had poorer prognosis compared with LMI patients; LMI patients with diabetes mellitus, dysphagia or temporal-occipital infarcts are prone to have poor prognosis.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Mesenchymal stem cells (MSCs) are an effective therapeutic strategy to delay aging in dogs, they are prone to aging and have poor genetic stability when cultured for a long time in vitro. Therefore, it is of great significance to explore a method to improve the anti-aging ability of MSCs. Previous studies have shown that sirtuin 6 (SIRT6) plays an important role in anti-aging. This study constructed MSCs with overexpressed SIRT6 gene. Through Giemsa staining and senescence-associated β-galactosidase staining, it was found that SIRT6 significantly enhances the anti-aging capacity of MSCs. Transmission electron microscopy imaging and the detection of oxidative stress-related indicators revealed that SIRT6 improves the anti-aging capacity of MSCs by maintaining mitochondrial homeostasis and reducing oxidative stress levels. Transcriptome sequencing analysis revealed that SIRT6 mainly acted on phosphatidylinositol-3-kinase, mitogen-activated protein kinase and other aging and inflammation related pathways. In the establishment and verification of aging models in mice and dogs, it was found that the spatial memory ability of the model mice was significantly increased after intravenous transplantation of SIRT6 overexpression cells, the organ index was also significantly changed, and the anti-oxidative capacity of the dogs and mice blood was improved. The morphology of the spleens and livers in the SIRT6 overexpression cell treatment group could be effectively restored, and the expression levels of aging and inflammation-related proteins were significantly decreased. This study provides a new idea for the study of SIRT6-mediated anti-aging of MSCs.
Animals ; Dogs ; Mesenchymal Stem Cells/metabolism* ; Sirtuins/genetics* ; Aging/physiology* ; Mice ; Oxidative Stress ; Mesenchymal Stem Cell Transplantation

Objective To explore the value of preoperative ultrasound examination in the prediction of restenosis of arteriovenous fistula(AVF)after percutaneous transluminal angioplasty(PTA)in hemodialysis patients.Methods A case-control trial was conducted on 225 hemodialysis patients who undergoing PTA due to AVF in our hospital January 2023 to May 2024.After 3 months of follow-up,they were divided into a patency group(n=204)and a restenosis group(n=21)according to the occurrence of postoperative restenosis.The preoperative clinical data and ultrasound parameters were compared between the groups.Binary logistic regression analysis was used to identify the independent factors for AVF restenosis after PTA.Receiver operating characteristic(ROC)curve was drawn to evaluate the value of preoperative stenosis length in the prediction of the restenosis after PTA.Results There were significant differences in preoperative internal diameter at the site of stenosis,stenosis length,stenosis number,intimal thickness,and brachial artery flow between the 2 groups(P<0.05).Preoperative stenosis length(OR=1.856,95%CI:1.350～2.552,P<0.001)was an independent factor of AVF restenosis in hemodialysis patients after PTA.ROC curve analysis showed that the area under the curve of preoperative stenosis length in predicting restenosis after PTA was 0.868(95%CI:0.784～0.953,P<0.001),with a sensibility and specificity of 85.7%and 80.4%,respectively.Conclusion Preoperative stenosis length may be an independent factor for AVF restenosis after PTA in hemodialysis patients.