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 analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group （Zhideke granules， 9.45 g/kg）； they were given ultrapure water or relevant medicine， twice a day， every 6-8 h， for 3 consecutive days. Serum， urine and feces samples of rats were collected， and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules； their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules， 16 prototype components （i.g. irisflorentin， baicalin， chlorogenic acid） and 11 metabolites （i.g. hydration products of kaempferol or luteolin， methylation products of chlorogenic acid， and hydroxylation products of baicalin） were identified in serum， urine and feces of rats. Among them， 8 prototype components and 4 metabolites were identified in serum samples； 10 prototype components and 7 metabolites were identified in urine samples； 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin， irisflorentin，chlorogenic acid， and the main metabolic pathways included methylation， hydroxylation， glucuronidation.

Objective:To study the feasibility of magnetic resonance imaging(MRI)technique with amide proton transfer(APT)in predicting the prognosis of cerebral stroke.Methods:A total of 71 patients with acute cerebral stroke who admitted to the Nanjing First Hospital,Nanjing Medical University from September 2022 to May 2023 were selected.All of them underwent the test of National Institute of Health Stroke Scale(NIHSS),and received the MRI examination with chemical exchange saturation transfer(CEST).According to the modified Rankin scale(mRS)values of 1-month follow-up,they were divided into favorable recovery group(mRS<2,44 cases)and poor group(mRS≥2,27 cases).The asymmetric magnetization transfer ratio(MTRasym)image(APT)was obtained by analyzing data with special software.And then,the difference(△APTw)of APT values between ischemic zone and contralateral normal tissue was further calculated.The △APTw values of two groups were compared and analyzed,and the Pearson correlation analysis was adopted to analyze the correlation among △APTw,NIHSS and mRS.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of ROC curve was calculated.Results:There were significant positive correlations among △APTw,NIHSS and mRS scores(R2=0.659,0.522,P<0.001),and the differences of △APTW,NIHSS and mRS scores between the favorable recovery group and poor group were significant(t=5.73,6.36,13.92,P<0.05),respectively.The AUC value was 0.886,and the sensitivity and specificity of prediction were respectively 77.8%and 95.5%.The positive and negative predictive values were respectively 91.3%and 87.5%.Conclusion:APT imaging technique has feasibility in predicting the prognosis of acute cerebral ischemic stroke.

Objective:To investigate the current status of exercise behavior in patients with colorectal cancer comorbid diabetes during chemotherapy, and to explore the pathways and effects of influencing factors using structural equation model, so as to provide reference for improving exercise behavior in patients with colorectal cancer comorbid diabetes during chemotherapy.Methods:From December 2022 to April 2023, 127 patients with colorectal cancer comorbid diabetes who received chemotherapy in Zhongshan Hospital Affiliated to Fudan University were selected by convenience sampling method as the research object. Self-designed general data questionnaire and exercise management ability questionnaire were used for cross-sectional investigation, and structural equation model was used to analyze the influencing factors of exercise behavior.Results:A total of 124 patients were included, including 95 males and 29 females, aged 39-90 (65.22 ± 8.87) years. The exercise level of patients with colorectal cancer comorbid diabetes during chemotherapy was lower, and the total weekly exercise was (3.70 ± 3.50) METs. Exercise ability, self-efficacy and social support were independent influencing factors of exercise behavior ( β = 1.796, 2.070, -0.944, all P<0.05). Conclusions:The exercise behavior of patients with colorectal cancer comorbid diabetes during chemotherapy is affected by multiple factors, self-efficacy, social support and exercise ability are independent influencing factors of exercise behavior. Improving exercise ability and enhancing self-efficacy is an effective way to improve exercise management of patients with colorectal cancer comorbid diabetes.

Objective:To investigate the status quo of the knowledge, attitude and practice (KAP) of standardized insulin injection at home in Shanghai community diabetic patients and analyze its influencing factors.Methods:In this cross-sectional study, totally 1 947 diabetic patients who signed to be managed by 21 community health service centers in Fengxian District, Shanghai from May to October 2020 who used insulin pen injections at home were selected by continuous enrolment. They were investigated with a general information questionnaire and a questionnaire on KAP of standardized insulin injection. Univariate analysis and multiple linear regression were used to analyze the influencing factors of patients' KAP of standardized insulin injection at home. A total of 1 947 questionnaires were distributed, and 1 697 valid questionnaires were recovered, with an effective recovery rate of 87.2%.Results:The total KAP score of insulin standard injection in the 1 697 diabetic patients was (51.01±6.81) , which was at a moderate level. Among all the items in the questionnaire, the 3 items with the lowest compliance rate were: checking the injection site every time before insulin injection (14.4%) , agreeing to put the discarded insulin needles into the capped hard-shell container (16.1%) , agreeing to and implementing insulin pen needle replacement after each use (20.6%) . Multiple linear regression analysis showed that age, education, type of medical insurance, and whether they had received insulin injection guidance were the influencing factors to the KAP of standardized insulin injection at home ( P<0.01) , which accounted for 8.6% of the total variation. Conclusions:Community medical staff should pay attention to the health education of insulin injection at home for diabetic patients, improve the content and form of education based on the characteristics of the community population, thereby improving the compliance rate of injection site inspection, replacement of insulin pen needles and standardized disposal of discarded needles, further standardizing insulin injection behavior, and improving clinical outcomes such as glycemic control in patients.

OBJECTIVE：To optimize the extraction technology of Zhideke granules. ME THODS：The extraction technology （water extraction ，alcohol extraction ，water extraction and ethanol precipitation ）of Zhideke granules was initially screened by ammonia-induced cough experiment and xylene-induced ear swelling experiment in mice. Based on its preparation route ，the immersion time of medicinal materials containing volatile oil was investigated with water absorption as index firstly. The single factor test was adopted to investigate the amount of water added and the extraction time taking the volatile oil yield as index to optimize the extraction technology of medicinal materials containing volatile oil. Taking the contents of irisflorentin and total flavonoids as indicators ，on the basis of single factor investigation ，orthogonal test was adopted to examine the influence of three factors including the amount of water added ，extraction time and extraction frequency ，so as to optimize the water extraction technology of Zhideke granules and the validation tests were conducted. RESULTS ：The results of pharmacodynamics experiment showed that the cough latency of mice in water extract low-dose and high-dose groups （6.34，12.68 g/kg，by crude drug ）and water-extraction alcohol-precipitation extract high-dose group （12.68 g/kg，by crude drug ）were significantly longer than those inmodel group ，and the number of cough within 2 minutes was significantly reduced （P＜0.05 or P＜0.01）. Compared with model group ， the ear swelling of mice in water extract low-dose and high-dose groups （6.34，12.68 g/kg，by crude drug），ethanol extract high-dose group （12.68 g/kg，by crude drug） and water-extraction alcohol-precipitation extract hig dose group （12.68 g/kg，by crude drug ） were decreased significantly （P＜0.05 or P＜0.01）. The swelling inhibition rates were 42.26％，55.08％，33.49％，51.56％，39.57％ and 44.36％ in low-dose and high-dose groups of water extract ，alcohol extract ， water-extraction and alcohol-precipitation extract respectively ，indicating that the water extract had better antitussive and anti-inflammatory effects. The optimal extraction technology of volatile oil was adding 5-fold water ，soaking for 30 minutes，and extracting for 3 hours. The optimal water extraction technology was adding 12-fold water ，extracting for 3 times after soaked for 50 min，lasting for 1 h each time. Results of 3 times of validation tests showed that average content of irisflorentin in the extract obtained by optimal technology was 76.47 μg/g（RSD＝ 2.15％，n＝3）and the average content of total flavonoids was 92.45 mg/g（RSD＝0.48％，n＝3）. CONCLUSIONS ：The optimal extraction technology of Zhideke granules is stable and feasible.

Objective:To investigate the effect of different solutions to prevent nasal intestinal blockage.Methods:Tottaly 199 cases of enteral nutrition treatment were selected from June 2018 to May 2019 and were randomly divided into three groups: warm boiled water group (67 cases), sugar-free cola group (67 cases), alpha-chymotrypsin group (65 cases). The rate of nasointestinal obstruction, the rate of nasointestinal obstruction, the rate of catheter patency maintenance, the rate of recanalization and the incidence of complications in three different enteral nutrition treatment cycles (< 7 days, 7-29 days, ≥ 30 days) were compared.Results:The catheter blockage rate in warm boiled water group was 20.9%(14/67) and in sugar-free cola group was 3.0%(2/67). The patency maintenance time in warm boiled water group was (8.83±1.84)days and in sugar-free cola group was (9.92±1.63) days ( t value was 2.182). The recanalization rate after blockage in warm boiled water group was 21.4%(3/14) and in sugar-free cola group was 100.0%( χ 2 value was 5.021, P < 0.05). The catheter blockage rate in sugar-free cola group was significantly lower than that in warm boiled water group, the catheter maintenance time and recanalization rate after blockage were significantly higher than that in warm boiled water group, the difference was significant ( P < 0.05). There was no significant difference between sugar-free cola group and alpha-chymotrypsin group in catheter blockage rate, catheter blockage rate, recanalization rate after blockage and incidence of complications( P > 0.05). The catheter blockage rate was 0 in patients with enteral nutrition treatment cycle < 7 days. The catheter blockage rate was 11.9%(8/67) (warm boiled water group) , 1.5%(8/67) (sugar-free cola group) and 1.5%(8/67) (alpha-chymotrypsin group) in patients with enteral nutrition treatment cycle 7-29 days. The catheter blockage rate was 9.0%(6/67) (warm boiled water group), 1.5%(1/65, sugar-free cola group) and 3.1%(2/67)(alpha-chymotrypsin group) in patients with enteral nutrition treatment cycle >30 days. The catheter blockage rate in sugar-free cola group and alpha-chymotrypsin group was significantly lower than that in warm boiled water group ( χ 2 values were 4.325-5.836, P<0.05) and there was no significant differences between the sugar-free cola group and the alpha-chymotrypsin group ( P>0.05). Conclusion:Sugar-free cola and alpha-chymotrypsin can effectively reduce the incidence of catheter blockage and complications, prolong the catheter patency and improve the recanalization rate after blockage, especially for patients with enteral nutrition treatment cycle longer than one week.

Objective: To investigate the expression level of IL-32 in peripheral blood mononuclear cells (PBMCs) and its correlation with serum biochemical indices of liver function test and HBV DNA load in chronic hepatitis B (CHB) patients with PEG IFN-α-2a treated. Methods: Thirty CHB patients with PEG IFN-α-2a treated (CHB group) and thirty normal health donors (health group) were enrolled in the study. Total RNA in PBMCs was extracted by using TRIzol. Than IL-32 mRNA level was assayed by using Real-time PCR. The correlation between IL-32 and ALT, AST, TBIL, HBV DNA load was analyzed using pearson′s correlation analysis, respectively. Results: IL-32 expression level in CHB group was significantly lower than that of health group. Moreover, the difference between them was statistically significant (P=0.000). IL-32 level was positively correlated with serum ALT and AST, respectively (P=0.035, P=0.032), but was not correlated with ALB and HBV DNA load (P=0.856, P=0.580). Conclusions IL-32 expression level was decreased in CHB patients with PEG IFN-α-2a Treated and was associated with the severity of inflammation.

The concept and significance of readiness for hospital discharge, measuring tools, application status, shortcomings and prospects of readiness for hospital discharge among patients with chronic diseases were reviewed in this article, with attempts to draw more attention to the readiness for hospital discharge among patients with chronic diseases in clinical practice and provide theoretical basis for forming the intervention plan suitable for China.

Objective To understand the hospital discharge readiness and discharge instruction quality in chronic disease patients and to analyze the correlation between them. Methods Totals of 602 chronic disease patients of related departments from 7 ClassⅢGrade A hospitals in Shanghai were selected by convenience sampling. All of them were investigated with the general information questionnaire, Readiness for Hospital Discharge Scale (RHDS) and Quality of Discharge Teaching Scale (QDTS), and their data were analyzed. Results Among those patients, the scores of hospital discharge readiness and discharge instruction quality were (8.01±1.41) and (8.65±1.29) out of 10 respectively. The score of hospital discharge readiness had a positive correlation with the score of discharge instruction quality with a statistical difference (r=0.507, P＜ 0.01). Conclusions Hospital discharge readiness and discharge instruction quality of chronic disease patients are all in high levels and with a positive correlation. Nurses should enrich the content of discharge instruction to improve the quality of discharge instruction by appropriate instruction skills and to improve the hospital discharge readiness.