Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.

Objective To compare the value of ultrashort echo time(UTE)and T1W sequences for detecting bone erosions of gouty arthritis.Methods Forty-four gouty patients were prospectively enrolled,including 32 cases with affected feet and 12 cases with affected knee.MR UTE and T1W sequence scanning of the affected area were performed,and subjectively scoring of imaging quality of 2 kinds of MRI were evaluated,respectively.Then total number and total score of bone erosions of each case were calculated according to all affected bones.Taken DECT as reference standard,the efficacy of UTE and T1WI for detecting bone erosions was assessed through comparing with DECT using Kappa coefficient.Results The imaging quality score of T1WI was lower than that of DECT(all P＜0.05),while no significant difference was found between UTE and DECT(all P＞0.05).There was high agreement between UTE and DECT for detecting bone erosions(κ=0.949),while the agreement between T1WI and DECT ranged from good to high(κ=0.718 to 0.805).The total number and total score of bone erosions based on T1WI were significantly lower than those based on DECT(all P＜0.05),while no significant difference was found between UTE and DECT(all P＞0.05).Conclusion UTE was better than T1WI for detecting bone erosions of gouty arthritis.

Objective: To investigate the interactive effects of prenatal and postnatal factors on overweight and obesity in preschool children, so as to provide evidence for subsequent planning of prevention strategies and intervention measures. Methods: Between October 2020 and June 2021, a convenience cluster sample of 918 preschool children from four kindergartens in Xuzhou urban area underwent questionnaire surveys and physical examinations. The Chi square test was used to compare intergroup differences in overweight and obesity prevalence. Multivariate Logistic regression analysis was employed to investigate the effects of prenatal and postnatal factors, as well as their interactions, on overweight and obesity in preschool children. Results: The prevalence of overweight and obesity among preschool children was 30.8%, with boys exhibiting a higher rate (37.0%) than girls (24.8%). Statistically significant differences in overweight and obesity prevalence were observed across age groups, genders, paternal pre pregnancy body mass index (BMI), paternal educational level, delivery mode, antibiotic use within the six months after birth, and rapid weight gain during infancy ( χ 2=5.08-17.67, all P <0.05). After adjusting for confounding factors such as age, gender, the only child, parental educational level and parental average monthly income, interaction analysis revealed that when the father was overweight or obese before conception, children delivered by caesarean section had an increased risk of overweight or obesity ( OR= 2.05 , 95%CI =1.02-3.39), and children with rapid weight gain during infancy also had an increased risk ( OR=2.05, 95%CI = 1.08 -3.88) (both P <0.05). Gender stratified analysis revealed that the interaction between paternal pre pregnancy BMI and mode of delivery on overweight and obesity was more pronounced among girls ( OR=4.00, 95%CI=1.51-10.58, P <0.05). While the interaction between the father s pre pregnancy BMI and rapid weight gain during infancy was more pronounced in boys ( OR= 2.85 , 95%CI=1.14-7.08, P <0.05). No significant interactions between prenatal and postnatal factors on overweight and obesity in preschool children were observed (all P >0.05). Conclusions Multiple prenatal and postnatal factors influence overweight and obesity in preschool children. Attention should be paid to mode of delivery and infant weight gain, particularly when the father is overweight or obese, to reduce the risk of overweight and obesity in preschool children.

Objective To explore the differences in the radiological features,clinical,and laboratory indicators of frequent versus infrequent gout flares in the feet and ankles using dual-energy computed tomography(DECT).Methods A retrospective selection was made on 385 gout patients,who were divided into the frequent flare group(≥2 gout attacks per year,219 cases)and the infre-quent flare group(<2 gout attacks per year,166 cases).Clinical data,laboratory indicators,and DECT imaging findings were col-lected for statistical analysis.Binary logistic regression was used to analyze the independent risk factors for frequent gout flares and receiver operating characteristic(ROC)curve was plotted.Results Statistically significant differences were found between the fre-quent flare group and the infrequent flare group in terms of disease duration,body mass index(BMI),blood pressure,triglyceride(TG),serum uric acid(SUA),monosodium urate(MSU)crystal deposition,total volume of MSU crystals,maximum diameter of individ-ual tophi,number of affected joints,bone erosion,maximum depth of bone erosion,soft tissue swelling,bone proliferation and sclero-sis,and joint space narrowing(P<0.05).SUA levels,MSU crystal deposition,total volume of MSU crystals,and maximum depth of bone erosion were identified as independent risk factors for frequent gout(P<0.05).Both the combination of four factors model and the maximum depth of bone erosion model had better diagnostic efficacy.Conclusion Gout patients with high SUA levels,MSU crystal deposition,larger total volume of MSU crystals,and greater maximum depth of bone erosion are more likely to experience frequent gout attacks.Patients with bone erosion depth>3.200 mm are more likely identified early as having frequent gout.

Objective To understand the current status and influencing factors of microbial contamination of dental unit waterlines(DUWLs)of secondary and lower medical institutions in Wuhan,and provide scientific basis for for-mulating prevention and control measures.Methods A stratified convenience sampling method was adopted to con-duct questionnaire survey on 248 dental medical institutions in 15 districts of Wuhan City,DUWLs from 44 medical institutions were sampled and detected according to hospital levels.Results Among disinfection and maintenance management measures for source water and waterlines,the highest implementation rate was the installation rate of anti-suction dental handpiece(73.39％,182/248),but only 16.48％(30/182)of institutions regularly conducted the detection on anti-suction function;The lowest was the daily disinfection rate of water storage tanks(17.53％,17/97).A total of 132 water specimens were collected from 44 medical institutions,with a qualified rate of microbi-al detection of 56.06％.The qualified rates for secondary,primary,and unclassified medical institutions were 77.78％,50.00％,and 50.72％,respectively,with statistically significant differences(P＜0.05).The qualified rates of microbial detection for source water,handpiece water,and three-way syringe water were 59.09％,50.00％,and 59.09％,respectively,with no statistically significant difference(P＞0.05).Univariate analysis re-sults showed that medical institutions that regularly conducted chemical disinfection on DUWLs,understood DU-WLs waterline cleaning and disinfection standards,regularly performed microbial monitoring on diagnosis and treat-ment water,qualified source water,and flushed waterlines for 3 minutes before and after daily consultations had a higher qualified rate of microbial detection in DUWLs diagnosis and treatment water,and the differences were all statistically significant(all P＜0.05).Conclusion The contamination status of DUWLs in secondary and lower medical institutions in Wuhan is relatively serious.It is recommended to focus on strengthening the training of rele-vant regulations,installing inlet filters,regularly detecting the anti-suction function of dental handpieces,imple-menting chemical disinfection and microbial monitoring on waterlines,standardizing the implementation of flushing before and after diagnosis and treatment,and strengthening the disinfection and use management of independent wa-ter storage tanks to control contamination.

Objective To explore the differences in the radiological features,clinical,and laboratory indicators of frequent versus infrequent gout flares in the feet and ankles using dual-energy computed tomography(DECT).Methods A retrospective selection was made on 385 gout patients,who were divided into the frequent flare group(≥2 gout attacks per year,219 cases)and the infre-quent flare group(<2 gout attacks per year,166 cases).Clinical data,laboratory indicators,and DECT imaging findings were col-lected for statistical analysis.Binary logistic regression was used to analyze the independent risk factors for frequent gout flares and receiver operating characteristic(ROC)curve was plotted.Results Statistically significant differences were found between the fre-quent flare group and the infrequent flare group in terms of disease duration,body mass index(BMI),blood pressure,triglyceride(TG),serum uric acid(SUA),monosodium urate(MSU)crystal deposition,total volume of MSU crystals,maximum diameter of individ-ual tophi,number of affected joints,bone erosion,maximum depth of bone erosion,soft tissue swelling,bone proliferation and sclero-sis,and joint space narrowing(P<0.05).SUA levels,MSU crystal deposition,total volume of MSU crystals,and maximum depth of bone erosion were identified as independent risk factors for frequent gout(P<0.05).Both the combination of four factors model and the maximum depth of bone erosion model had better diagnostic efficacy.Conclusion Gout patients with high SUA levels,MSU crystal deposition,larger total volume of MSU crystals,and greater maximum depth of bone erosion are more likely to experience frequent gout attacks.Patients with bone erosion depth>3.200 mm are more likely identified early as having frequent gout.

Objective To compare the value of ultrashort echo time(UTE)and T1W sequences for detecting bone erosions of gouty arthritis.Methods Forty-four gouty patients were prospectively enrolled,including 32 cases with affected feet and 12 cases with affected knee.MR UTE and T1W sequence scanning of the affected area were performed,and subjectively scoring of imaging quality of 2 kinds of MRI were evaluated,respectively.Then total number and total score of bone erosions of each case were calculated according to all affected bones.Taken DECT as reference standard,the efficacy of UTE and T1WI for detecting bone erosions was assessed through comparing with DECT using Kappa coefficient.Results The imaging quality score of T1WI was lower than that of DECT(all P＜0.05),while no significant difference was found between UTE and DECT(all P＞0.05).There was high agreement between UTE and DECT for detecting bone erosions(κ=0.949),while the agreement between T1WI and DECT ranged from good to high(κ=0.718 to 0.805).The total number and total score of bone erosions based on T1WI were significantly lower than those based on DECT(all P＜0.05),while no significant difference was found between UTE and DECT(all P＞0.05).Conclusion UTE was better than T1WI for detecting bone erosions of gouty arthritis.

Objective To understand the current status and influencing factors of microbial contamination of dental unit waterlines(DUWLs)of secondary and lower medical institutions in Wuhan,and provide scientific basis for for-mulating prevention and control measures.Methods A stratified convenience sampling method was adopted to con-duct questionnaire survey on 248 dental medical institutions in 15 districts of Wuhan City,DUWLs from 44 medical institutions were sampled and detected according to hospital levels.Results Among disinfection and maintenance management measures for source water and waterlines,the highest implementation rate was the installation rate of anti-suction dental handpiece(73.39％,182/248),but only 16.48％(30/182)of institutions regularly conducted the detection on anti-suction function;The lowest was the daily disinfection rate of water storage tanks(17.53％,17/97).A total of 132 water specimens were collected from 44 medical institutions,with a qualified rate of microbi-al detection of 56.06％.The qualified rates for secondary,primary,and unclassified medical institutions were 77.78％,50.00％,and 50.72％,respectively,with statistically significant differences(P＜0.05).The qualified rates of microbial detection for source water,handpiece water,and three-way syringe water were 59.09％,50.00％,and 59.09％,respectively,with no statistically significant difference(P＞0.05).Univariate analysis re-sults showed that medical institutions that regularly conducted chemical disinfection on DUWLs,understood DU-WLs waterline cleaning and disinfection standards,regularly performed microbial monitoring on diagnosis and treat-ment water,qualified source water,and flushed waterlines for 3 minutes before and after daily consultations had a higher qualified rate of microbial detection in DUWLs diagnosis and treatment water,and the differences were all statistically significant(all P＜0.05).Conclusion The contamination status of DUWLs in secondary and lower medical institutions in Wuhan is relatively serious.It is recommended to focus on strengthening the training of rele-vant regulations,installing inlet filters,regularly detecting the anti-suction function of dental handpieces,imple-menting chemical disinfection and microbial monitoring on waterlines,standardizing the implementation of flushing before and after diagnosis and treatment,and strengthening the disinfection and use management of independent wa-ter storage tanks to control contamination.