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

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 explore the effect and mechanism of Slc1a2 overexpression on cognitive dysfunction in sleep-deprived mice.Methods A total of 130 mice were divided into five groups:normal sleep(NS),NS+ov-Slc1a2,sleep deprivation(SD),SD+ov-NC,and SD+ov-Slc1a2,with 26 mice in each group.The SD mice model was established using an automatic system based on a rotating rod,and overexpress Slc1a2 adenovirus was injected into the prefrontal cortex(PFC).Immunofluorescence and Western blotting were used to detect the expression of Slc1a2 in the mouse PFC.Electrophysiological tests were used to evaluate non-rapid eye movement(NREM)sleep time,rapid eye movement(REM)sleep time,and wakefulness time in mice.Real-time quantitative PCR was used to detect the expression of glutamate(Glu)and gamma-aminobutyric acid(GABA)metabolic enzymes in the mouse PFC.Whole-cell patch-clamp recording was used to detect the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSC)in mouse PFC.Immunofluorescence was used to detect the proportion of GABA-positive cells in the mouse PFC.The C11-BODIPY fluorescent probe was used to detect lipid reac-tive oxygen species(ROS)levels in mouse PFC.Commercial kits were used to detect Fe2+and malondialdehyde(MDA)levels in the mouse PFC.Cognitive function in mice was evaluated using the open field,novel object recognition,and Y-maze tests.Results Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index increased significantly,while wakefulness time decreased significantly in the NS+ov-Slc1a2 group(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD group and the SD+ov-NC group were significantly decreased,whereas wakefulness time was significantly increased(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the mouse PFC decreased significantly,whereas lipid ROS,Fe2+,and MDA levels increased significantly(all P＜0.05).Compared with the SD and SD+ov-NC groups,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD+ov-Slc1a2 group increased significantly,whereas the wakeful-ness time decreased significantly(all P＜0.05).The percentage of Slc1a2+GFAP+cells,the expression of Slc1a2 protein,the expression of Glul,Slc6a1,and Abat mRNA,the frequency and amplitude of mEPSC,and the proportion of GABA-positive cells in the mouse PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Conclusion Ectopic overexpres-sion of Slc1a2 in the PFC can improve sleep disorders in SD mice,reduce the damage caused by SD to excitatory synaptic transmission and GABAergic neuron function in the PFC,and alleviate cognitive impairment and anxiety-like behavior in these mice.Its mechanism may be related to the improvement of Glu/GABA metabolic imbalance in the PFC and inhibition of ferroptosis.

Objective:To explore inhibitory effect of Tianzhi granule on neuroinflammation in vascular dementia(VD)rats.Methods:Sixty rats were randomly divided into Sham group,VD group,TZG-L group and TZG-H group,with 15 rats in each group.Bilateral common carotid artery occlusion was used to construct VD rats model,Sham group was not ligated.Rats in TZG-L group and TZG-H group were gavaged with Tianzhi granule 5 g/kg,20 g/kg every day,while rats in Sham group and VD group were gavaged with same amount of normal saline for 8 weeks.Y-maze test was used to detect cognitive ability of rats;Nissl staining and FJC staining were used to assess neuronal damage;TUNEL staining was used to detect neuronal apoptosis;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 protein levels in temporal cortex tissue.PC12 cells was divided into Control group,Glutamate group,TZG-L group and TZG-H group.Glutamate(20 μmol/L)was used to construct neuron injury model.TZG-L group and TZG-H group were added with Tianzhi granule 1 mg/ml,4 mg/ml.Neurons in each group were incubated for 48 h.CCK8 method and TUNEL staining were used to detect activity and apoptosis of neurons;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,Nrf2,HO-1 protein levels in cells.Results:Compared with Sham group,cognitive ability of rats in VD group were decreased,TUNEL positive neurons ratio was increased,Bcl-2 level was decreased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 levels were increased(all P<0.05).Compared with VD group,cognitive ability of rats in TZG-L group and TZG-H group were increased,TUNEL positive neurons ratio was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO levels were decreased(all P<0.05).Morphology of neurons in control group were normal;compared with control group,neurons in Glutamate group were swollen,activity of neurons was decreased,apoptosis rate was increased,Bcl-2 level was decreased,Bax,Caspase-3,Nrf2,HO-1 levels were increased(all P<0.05);compared with Glutamate group,cell damage in TZG-L group and TZG-H group were reduced,activity of neurons was increased and apoptosis rate was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3 levels were decreased(all P<0.05).Conclusion:Tianzhi granule can inhibit neuronal apoptosis and expression of NLRP3 inflammasome in VD rats,inhibit activa-tion of microglia/astrocytes and neutrophil infiltration,improve neuroinflammation of VD,which may play a role by activating Nrf2/HO-1 signaling pathway in neurons.

Objective To establish and test a 3-year prognosis model for elderly intertrochanteric fractures after intramedullary nail fixation.Methods A total of 205 elderly patients with intertrochoteric fracture of femur who underwent intramedullary nail fixation in our hospital from April 2019 to April 2021 were selected for observation study,followed up for 3 years after surgery,according to the Harris score,they were divided into the good group and the poor group.Univariate analysis was conducted to investigate the influencing factors of disease prognosis in the two groups 3 years after surgery.After the variables were screened by LASSO regression and cross-validation method,the independent influencing factors of the 3-year postoperative prognosis were analyzed by multi-factor Logistic regression,and the prediction model of the nomogram was built,and the model was evaluated and validated.Results Among 205 elderly patients with intertrochanteric fractures of the femur who underwent intramedullary nailing fixation,201 were followed up for 3 years.Among them,148 patients had a Harris score of ≥70 points,while 53 patients had a score of＜70 points.Univariate analysis results showed that the poor group had a higher proportion of patients with age,stroke,osteoporosis,Evans-Jensen type Ⅲ and Ⅳ fractures,poor intraoperative reduction,and a tip-apex distance of ≥ 30 mm compared to the good group,and had a lower lateral wall thickness than the good group,the difference was statistically significant(P＜0.05).LASSO regression analysis and cross-validation were used to screen variables.Multivariate Logistic regression analysis showed that stroke(OR=2.127,95％CI:1.478-3.061)and fracture Evans-Jensen classification Ⅲ(OR=1.149,95％CI:1.105-1.195)and type Ⅳ(OR=1.187,95％CI:1.143-1.233),intraoperative reduction was not good(OR=3.290,95％CI:2.319-4.668),apex distance ≥ 30 mm(OR=1.413,95％CI:1.066-1.874)was an independent associated risk factor for disease outcome 3 years after surgery,the external wall thickness(OR=0.600,95％CI:0.428-0.841)was an independent correlated risk factor for 3-year prognosis(P＜0.05).Based on the results of multiple factors,a nomogram prediction model was drawn,and the results showed that the model had certain predictive value for the disease outcome three years after surgery.The evaluation and verification results showed that when the threshold probability was 0-96％,the model had good clinical applicability and positive clinical net benefit.Conclusion Stroke,fracture Evans-Jensen classification Ⅲ and Ⅳ,poor intraoperative reduction,apical distance ≥30 mm,and lateral wall thickness are independent and relevant factors for 3-year prognosis of senile intertrochanteric fractures after intramedullary nail fixation.The establishment of a nematographic model has good predictive value for postoperative long-term prognosis and positive clinical net benefit.It can be used as an effective model to predict the long-term prognosis of postoperative disease.

Background:Nutritional risk is highly prevalent among gastric cancer patients,yet accurate screening tools remain lacking.Aims:To construct and validate a nutritional risk prediction model for gastric cancer inpatients.Methods:From August 2023 to July 2024,a total of 295 gastric cancer inpatients admitted to the First Hospital of Qinhuangdao were enrolled,and divided into the model group(n=206)and validation group(n=89)at a ratio of 7∶3.Nutritional screening was performed in the model group using the nutritional risk screening 2002(NRS 2002)score.Univariate analysis and multivariate Logistic regression analysis were employed to identify the independent risk factors for nutritional risk,and a prediction model was constructed.The Hosmer-Lemeshow goodness-of-fit test was used to evaluate the consistency between the model constructed and NRS 2002 score.The predictive performance was assessed using ROC curve and validated in the independent cohort.Risk stratification was performed based on the cut-off value derived from the ROC curve,and the nutritional risk in different subgroups of the model group and validation group was assessed.Results:Multivariate Logistic regression analysis indicated that age≥68 years,body mass index(BMI)≤22 kg/m2,anorexia,dysphagia and anemia were the independent risk factors for nutritional risk in gastric cancer patients in the model group(all P<0.05).The prediction model had good consistency with the NRS 2002 score(P=0.567).ROC curve showed that the area under the curve(AUC)of the prediction model for predicting nutritional risk were 0.840(95%CI:0.785-0.895,P<0.001)for the model group and 0.895(95%CI:0.831-0.958,P<0.001)for the validation group when the cut-off value was set at 9.5 points.The proportion of patients with nutritional risk in high-risk subgroup was significantly higher than that in low-risk subgroup in both model group and validation group(P<0.001).Conclusions:The prediction model based on age,BMI,anorexia,dysphagia and anemia can effectively identify nutritional risk in gastric cancer inpatients and may serve as a clinical reference tool.

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.

With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.

With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.

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.