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 explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.

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 Based on nuclear factor E2 associated factor 2(NRF2)/PTEN induced hypothesized kinase 1(PINK1)pathway,explored the ameliorating effect of rutaecarpine on chronic obstructive pulmonary disease(COPD)rats and its repairing effect on airway epithelial barrier.Methods COPD rat model were established by smoke combined with airway infusion of lipopolysaccharide;and were randomly divided into model group,control group,and experimental-L group,experimental-M group,experimental-H group,10 rats per group.Another 10 normal rats were selected as the normal group.Experimental-L,-M,-H groups were intraperitoneally injected 15,30 and 60 mg·mL-1 rutaecarpine at the dose of 10 mL·kg-1,respectively.The control group was received 4.05 x 10-2 mg·mL-1 prednisone acetate at the dose of 10 mL·kg-1 by gavage.The normal and model groups were given 0.9％NaCl by intraperitoneal injection.Six groups were treated for 28 days with once a day.The first second forced expiratory volume(FEV1)and forced vital capacity(FVC)of rats were measured by minor animal lung function tester.The levels of interleukin(IL)and interferon-γ(INF-γ)in alveolar lavage fluid were determined by enzyme-linked immunosorbent assay method.The expression levels of PINK1 and NRF2 proteins in the lung tissue were determined by Western blot.Results The levels of FEV1 in the experimental-M group,experimental-H group,control group,model group and normal group were(5.17±0.16),(6.36±0.12),(5.06±0.07),(2.24±0.20)and(6.84±0.11)mL;the levels of FVC were(6.71±0.13),(7.56±0.12),(6.81±0.07),(4.46±0.14)and(7.92±0.11)mL;the levels of IL-12 in alveolar lavage fluid were(7.08±0.51),(9.03±0.54),(7.92±0.79),(3.61±1.01)and(10.15±0.82)pg·mL-1;the levels of IL-9 in alveolar lavage fluid were(22.49±2.27),(15.02±1.41),(17.47±1.84),(38.72±1.28)and(11.78±0.94)pg·mL-1;the levels of INF-γ in alveolar lavage fluid were(13.18±0.54),(16.25±0.60),(15.23±0.43),(6.97±0.89)and(17.22±1.15)pg·mL-1;the relative expression levels of PINK1 protein were 1.10±0.06,1.30±0.09,1.18±0.15,0.42±0.03 and 1.61±0.05;the relative expression levels of NRF2 protein were 0.91±0.05,1.46±0.03,1.35±0.07,0.53±0.07 and 1.64±0.11,respectively.The differences of above indexes were statistically significant between the experimental-M group,experimental-H group,control group and the model group(all P＜0.05).Conclusion Rutaecarpine can inhibit inflammation,improve lung function and repair airway epithelial barrier in COPD rats,and its mechanism may be related to regulating NRF2/PINK1 pathway.

Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective Based on nuclear factor E2 associated factor 2(NRF2)/PTEN induced hypothesized kinase 1(PINK1)pathway,explored the ameliorating effect of rutaecarpine on chronic obstructive pulmonary disease(COPD)rats and its repairing effect on airway epithelial barrier.Methods COPD rat model were established by smoke combined with airway infusion of lipopolysaccharide;and were randomly divided into model group,control group,and experimental-L group,experimental-M group,experimental-H group,10 rats per group.Another 10 normal rats were selected as the normal group.Experimental-L,-M,-H groups were intraperitoneally injected 15,30 and 60 mg·mL-1 rutaecarpine at the dose of 10 mL·kg-1,respectively.The control group was received 4.05 x 10-2 mg·mL-1 prednisone acetate at the dose of 10 mL·kg-1 by gavage.The normal and model groups were given 0.9％NaCl by intraperitoneal injection.Six groups were treated for 28 days with once a day.The first second forced expiratory volume(FEV1)and forced vital capacity(FVC)of rats were measured by minor animal lung function tester.The levels of interleukin(IL)and interferon-γ(INF-γ)in alveolar lavage fluid were determined by enzyme-linked immunosorbent assay method.The expression levels of PINK1 and NRF2 proteins in the lung tissue were determined by Western blot.Results The levels of FEV1 in the experimental-M group,experimental-H group,control group,model group and normal group were(5.17±0.16),(6.36±0.12),(5.06±0.07),(2.24±0.20)and(6.84±0.11)mL;the levels of FVC were(6.71±0.13),(7.56±0.12),(6.81±0.07),(4.46±0.14)and(7.92±0.11)mL;the levels of IL-12 in alveolar lavage fluid were(7.08±0.51),(9.03±0.54),(7.92±0.79),(3.61±1.01)and(10.15±0.82)pg·mL-1;the levels of IL-9 in alveolar lavage fluid were(22.49±2.27),(15.02±1.41),(17.47±1.84),(38.72±1.28)and(11.78±0.94)pg·mL-1;the levels of INF-γ in alveolar lavage fluid were(13.18±0.54),(16.25±0.60),(15.23±0.43),(6.97±0.89)and(17.22±1.15)pg·mL-1;the relative expression levels of PINK1 protein were 1.10±0.06,1.30±0.09,1.18±0.15,0.42±0.03 and 1.61±0.05;the relative expression levels of NRF2 protein were 0.91±0.05,1.46±0.03,1.35±0.07,0.53±0.07 and 1.64±0.11,respectively.The differences of above indexes were statistically significant between the experimental-M group,experimental-H group,control group and the model group(all P＜0.05).Conclusion Rutaecarpine can inhibit inflammation,improve lung function and repair airway epithelial barrier in COPD rats,and its mechanism may be related to regulating NRF2/PINK1 pathway.