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 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 establish HPLC fingerprints of different polar parts of Zhuang medicine Calonyction muricatum ， and to study its spectrum-effect relationship with analgesic and anti-inflammatory effects. METHODS ：The total part ，ethyl acetate part，n-butanol part and water part of C. muricatum were prepared. HPLC fingerprints of different polar parts were established by HPLC method combined with the Similarity Evaluation System of TCM Chromatogramtic Fingerprint （2012A），and the common peaks were identified. Using writhing times and ear swelling degree in mice as analgesic and anti-inflammatory indexes ，analgesic and anti-inflammatory activity of different polar parts of C. muricatum were investigated. The correlation of the common peaks of HPLC fingerprint with analgesic and anti-inflammatory indexes was analyzed by grey correlation analysis ，bivariate correlation analysis and partial least square （PLS） method. RESULTS ： There were 11 common peaks for the different polar parts of C. muricatum ，and 5 components were identified by reference comparison，i.e. neochlorogenic acid （peak 3），chlorogenic acid （peak 5）， cryptochlorogenic acid （peak 6）， isochlorogenic acid A （peak 10），isochlorogenic acid C （peak 11）. The grey correlation analysis showed that the correlation between all common peaks and analgesic and anti- inflammatory effects were greater than 0.6 （except the correlation between peak 6 and analgesic effects ），showing correlation relationship ；the correlation of peaks 3，7 and 10 with analgesic and anti-inflammatory effects were all greater than 0.8，which was highly related. Bivariate correlation analysis showed that the correlation of peak 1，3，4，7，9，10，11 with analgesic and anti-inflammatory effects were all greater than 0.6，showing correlation relationship. PLS method showed that peaks 1，3，4，7，9，10，11 contributed greatly to playing an analgesic and anti-inflammatory role. CONCLUSIONS ：HPLC fingerprints of different polar parts of C. muricatum is established and five common peak components were identified. Neochlorogenic acid ，isochlorogenic acid A ，isochlorogenic acid C and chemical components represented by peaks 1，4，7，9 may be the pharmacodynamic substances of C. muricatum to exert analgesic and anti-inflammatory effects.

OBJECTIVE：To i nvestigate the spectrum-effect relationship of analgesic and anti-inflammatory effects of ethyl acetate extract from Zhuang medicine Stahlianthus involucratus from different habitats. METHODS ：Ten batches of S. involucratus from different habitats were used as samples to investigate the anti-inflammatory and analgesic activities of ethyl acetate extracts by xylene induced ear swelling test and acetic acid induced writhing test in mice. HPLC fingerprints of 10 batches of ethyl acetate extract from S. involucratus were established and their similarity was evaluated by using Similarity Evaluation System of TCM Chromatogram Fingerprint （2012 edition），and the common peaks were identified by comparison with the control. The spectrum-effect relationship of anti-inflammatory and analgesic effects of ethyl acetate extract from S. involucratus were analyzed on the basis of Pearson correlation coefficient （auricle swelling degree and writhing times in 15 min as pharmacodynamic indexes ）and Grey relational analysis （inhibition rate of ear swelling and analgesic rate as pharmacodynamic indexes ）. RESULTS ： batches of ethyl acetate extract from S. involucratus had obvious anti-inflammatory and analgesic effects ； inhibition rates of ear swelling in mice were 46.43％-55.16％，and the analgesic rates of mice were 45.56％-52.72％. A total of 18 common peaks were identified in 10 batches of samples ，andthe similarity between them and the control fingerprint was 0.994-0.997. Compared with substance control ，the pea ks 1，2 and 4 were identified as protocatechuic acid ， p-hydroxy- 0771-4953513。E-mail：liangjie1101@126.com benzoic acid and p-hydroxybenzaldehyde，respectively. Results of Pearson correlation analysis showed that peak 10 and peak 18 were significantly negative correlated with auricle swelling degree and writhing times in 15 min（r were values －0.853，－0.738，P values were 0.002，0.015，respectively）. Results of Gray correlation degree analysis showed that the correlation degree of 18 common peaks with inhibition rate of ear swelling and analgesic rate were all greater than 0.65；among them ，peaks 14，1（protocatechuic acid ），17，9，4（p-hydroxybenzaldehyde），2（p-hydroxybenzoic acid ）， 16，7 and 6 showed the relatively high correlation degree （correlation degree ＞0.7）；peak 1（protocatechuic acid ），17，14，9，16，2 （p-hydroxybenzoic acid ）and 4（p-hydroxybenzaldehyde）showed the relatively high correlation degree （correlation degree ＞0.7）. CONCLUSIONS：The ethyl acetate extract of S. involucratus show good anti-inflammatory and analgesic effects. Peak 1 （protocatechuic acid ），2（p-hydroxybenzoic acid ），10，14，17，18 may be its main active ingredients.

OBJECTIVE：To eval uate the effect of pharmacists intervention on opioid treatment and management in outpatients with cancer pain under multidisciplinary team （MDT）mode. METHODS ：Totally 120 outpatients with cancer pain were selected from outpatient department of our hospital from Jan. 2016 to Dec. 2018，and divided into observation group and control group according to random number table method ，with 60 cases in each group. After 1 month follow-up ，patients in the control group were given opioid analgesics and routine intervention according to pain degree ，while patients in the observation group were given same treatment as control group and pharmacist intervention based on MDT. The pain condition ，medication compliance condition ， quality of life （QOL）score，the incidence of ADR and satisfaction degree were observed in 2 groups before and after intervention . RESULTS：Follow-up were completed in 2 groups. After intervention ，NRS scores of 2 groups were significantly lower than before intervention；the observation group was significantly lower than the control group ；medication compliance scores and QOL scores of 2 groups were significantly higher than before intervention ，the observation group was significantly higher than the control group at the same time . With the prolongation of treatment time ，the number of patients with mild pain and general medication compliance in 2 groups increased gradually ，and the observation group were significantly higher than the control group at the same time；the number of patients with moderate , severe pain and low medication compliance were significantly decreased gradually ， and the observation group was significantly lower than the control group at the same time. The number of patients with good medication compliance in the observation group was significantly higher than that in the same group before intervention and the control group at the same time （P＜0.05 or P＜0.01）. There was no significant difference in the incidence of ADR between 2 groups（P＞0.05）. The satisfaction of pain control results ，doctors’treatment and pharmacists follow-up in the observation group were significantly higher than control group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Under MDT mode ，pharmacists participating in the management of opioid treatment for cancer pain outpatients can effectively relieve the pain ，and improve the medication compliance and quality of life .

Objective:To investigate the improvement and clinical effect of lip depilation with 810 nm semiconductor laser.Methods:Retrospective analysis was performed on female labial hair removal patients admitted to Bethune Hospital in Shanxi from January 2017 to October 2018. The patients who visited the clinic from January 2018 to October 2018 were taken as the experimental group, and those who visited the clinic from January 2017 to December 2017 were taken as the control group. A combination model of super hair removal(SHR) + hair removal(HR) was adopted to perform the treatment with 810 nm YfTON semiconductor freezing point laser hair removal. The experimental group was treated with surface anesthetic and SHR mode dumbbell sliding mode 8 J/cm 2+ HR mode with high energy (starting from the upper limit of reference energy value), and the patients were treated with local drum and chin coordination. In the control group, no surface anesthetic was applied, and SHR mode was used for linear round-trip sliding + HR mode for reference energy treatment. After the third and fifth treatment, the patients in the two groups were treated with a hair size of 1 cm×1 cm on one side of the mouth corner with heavy hair. A hair analyzer was used to count the number of similar hairs visible to the naked eye at a social distance of about 1 meter. The final hair removal rate was calculated as excellent (70%-90%, including 70%), as improvement (40%-70%, including 40%), as invalid (<40%). The depilation rate after 3 and 5 treatments was compared between the 2 groups, the number of treatments was analyzed, and the recurrence rate and comfort level of the patients were followed up 6 months after treatment. Wilcoxon rank sum test was used to compare the measurement data. Comparison of counting data was tested, and P<0.05 was considered statistically significant. Results:A total of 200 patients were included in this study, including 100 in the experimental group, with an age of (28.58±6.01) years. The control group included 100 patients (28.57±6.07) years old. The skin type of patients was performed according to Fitzpatrick and Chinese characteristics Ⅱ-Ⅳ. After statistical test, there were no statistically significant differences in age and skin type between the two groups. After half a year of follow-up, the average number of treatment times in the experimental group was 5(5, 6) times, lower than that in the control group 7(6, 8) times( T=-9.279, P<0.001). The three and five depilation rates of the experimental group were[70.0%(68.0%, 74.8%), 86.0%(83.0%, 88.0%)], and the final depilation rates of the experimental group were 89.0%(86.7%, 90.0%), all higher than those in the control group[40.0%(37.0%, 42.0%), 72.0%(70.0%, 74.0%), 86.5%(85.0%, 88.0%)]. The differences between the two groups were statistically significant ( T3=43.986, T5=25.151, Tfinal=5.547, all P< 0.001). The intermittent times of single sliding treatment in the experimental group ≤2 times, compared with the control group > 2 times, the comfort level was improved. No blisters or coloration occurred in any of the patients. Patients in the 2 groups were followed up for half a year after the last hair removal. In the 2 groups, there were sparse new fine hairs and soft hair growth that were not included in the hair count, and the included hairs were thinner than those before the treatment. Conclusions:Compared with the control group, the treatment cycle is shorter, the efficiency is higher and the comfort level of the patients is higher in the experimental group.

Objective:To investigate the improvement and clinical effect of lip depilation with 810 nm semiconductor laser.Methods:Retrospective analysis was performed on female labial hair removal patients admitted to Bethune Hospital in Shanxi from January 2017 to October 2018. The patients who visited the clinic from January 2018 to October 2018 were taken as the experimental group, and those who visited the clinic from January 2017 to December 2017 were taken as the control group. A combination model of super hair removal(SHR) + hair removal(HR) was adopted to perform the treatment with 810 nm YfTON semiconductor freezing point laser hair removal. The experimental group was treated with surface anesthetic and SHR mode dumbbell sliding mode 8 J/cm 2+ HR mode with high energy (starting from the upper limit of reference energy value), and the patients were treated with local drum and chin coordination. In the control group, no surface anesthetic was applied, and SHR mode was used for linear round-trip sliding + HR mode for reference energy treatment. After the third and fifth treatment, the patients in the two groups were treated with a hair size of 1 cm×1 cm on one side of the mouth corner with heavy hair. A hair analyzer was used to count the number of similar hairs visible to the naked eye at a social distance of about 1 meter. The final hair removal rate was calculated as excellent (70%-90%, including 70%), as improvement (40%-70%, including 40%), as invalid (<40%). The depilation rate after 3 and 5 treatments was compared between the 2 groups, the number of treatments was analyzed, and the recurrence rate and comfort level of the patients were followed up 6 months after treatment. Wilcoxon rank sum test was used to compare the measurement data. Comparison of counting data was tested, and P<0.05 was considered statistically significant. Results:A total of 200 patients were included in this study, including 100 in the experimental group, with an age of (28.58±6.01) years. The control group included 100 patients (28.57±6.07) years old. The skin type of patients was performed according to Fitzpatrick and Chinese characteristics Ⅱ-Ⅳ. After statistical test, there were no statistically significant differences in age and skin type between the two groups. After half a year of follow-up, the average number of treatment times in the experimental group was 5(5, 6) times, lower than that in the control group 7(6, 8) times( T=-9.279, P<0.001). The three and five depilation rates of the experimental group were[70.0%(68.0%, 74.8%), 86.0%(83.0%, 88.0%)], and the final depilation rates of the experimental group were 89.0%(86.7%, 90.0%), all higher than those in the control group[40.0%(37.0%, 42.0%), 72.0%(70.0%, 74.0%), 86.5%(85.0%, 88.0%)]. The differences between the two groups were statistically significant ( T3=43.986, T5=25.151, Tfinal=5.547, all P< 0.001). The intermittent times of single sliding treatment in the experimental group ≤2 times, compared with the control group > 2 times, the comfort level was improved. No blisters or coloration occurred in any of the patients. Patients in the 2 groups were followed up for half a year after the last hair removal. In the 2 groups, there were sparse new fine hairs and soft hair growth that were not included in the hair count, and the included hairs were thinner than those before the treatment. Conclusions:Compared with the control group, the treatment cycle is shorter, the efficiency is higher and the comfort level of the patients is higher in the experimental group.

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.