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ObjectiveBy observing the effect of Qianyang Yuyin granules on the phenotype of renal tubule epithelial cells， the intervention of Qianyang Yuyin granule on renal interstitial fibrosis was investigated. MethodThe renal tubular epithelial cells （HK-2） were treated with different concentrations of transforming growth factor （TGF）-β1 （5， 10， 15， 20， 25 μg·L-1） for 24 hours， and cell morphology and growth state were observed with an inverted phase contrast microscope. The 20 μg·L-1 was selected as the most appropriate concentration of TGF-β1 according to Western blot results for subsequent experiments. HK-2 cells were divided into six groups： blank group， TGF-β1 group （concentration of 20 μg·L-1）， low， medium， and high dose Qianyang Yuyin granule groups （concentration of 0.5， 1， 2 g·L-1）， and valsartan group （1 × 10-5 mol·L-1）. The cell activity was measured by cell proliferation and cell counting kit-8 （CCK-8）. The cell migration ability was detected by scratch test. The Transwell method was used to detect the invasiveness of cells. Western blot was used to detect levels of fibronectin （FN）， E-cadherin， α-smooth muscle activator （α-SMA）， Vimentin， collagen type Ⅰ（Col Ⅰ）， collagen type Ⅳ（Col Ⅳ）， and other related proteins. ResultTGF-β1 stimulating epithelial-mesenchymal transition （EMT） in renal tubular epithelial cells was time- and concentration-dependent. Compared with the blank group， higher concentration in the TGF-β1 group indicates longer intervention time and more obvious long spindle change of cells， and the migration and invasion ability of the cells was significantly enhanced. The protein expression level of FN， α-SMA， Vimentin， Col Ⅰ， and Col Ⅳ increased significantly （P<0.05， P<0.01）， while the expression level of E-cadherin protein decreased （P<0.05）. Compared with the TGF-β1 group， Qianyang Yuyin granule groups could maintain normal cell morphology， and the migration and invasion ability of the cells was inhibited. The protein expression level of FN， α-SMA， Vimentin， Col Ⅰ， and Col Ⅳ decreased （P<0.05， P<0.01）， and the expression of E-cadherin protein was significantly restored （P<0.05）. ConclusionQianyang Yuyin granule can reverse TGF-β1-induced interstitial transformation of renal tubular epithelial cells by reducing the phenotypic expression of mesenchymal cells and increasing the phenotypic expression of epithelial cells.
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Objective Optimizing the extraction process of prescription medicinal materials of hospital preparation of compound Yangshe granules. Methods A high performance liquid chromatograph (HPLC) quantitative method was established for deacetyl asperulosidicacid methyl ester (DME) and ferulic acid (FC) of the active ingredient. Based on the content of DME, FC and the yield of extract, the extraction process of compound Yangshe granule extract was optimized using central composite design-response surface methodology. Results The established HPLC method of quantification of active components in compound Yangshe granules met the requirements of method validation. The optimal extraction process optimized by central composite design-response surface methodology were as follows: the weight of extraction solvent was 12 times of the medicinal slices, the alcohol concentration was 73% and the extraction time was 60 min. Conclusion In this study, the quantitative method of active components in compound Yangshe granule by HPLC has been successfully established, and the optimized extraction process is simple and easy to operate with good repeatability.
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OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.
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Humans , Network Pharmacology , Quercetin , Medicine, Chinese Traditional , Molecular Docking Simulation , Esophageal Neoplasms , Drugs, Chinese HerbalABSTRACT
Objective:To optimize the extraction process of Shangke Huoxue Granule.Methods:Taking the factors of extraction solvent multiple, extraction time and extraction times as investigation factors, and extraction amount of ferulic acid, paeoniflorin and the ratio of extraction as comprehensive evaluation indices, one-factor experimental design and central composite design-response surface methodology were adopted to optimize the extraction process of Shangke Huoxue Granule.Results:The binomial fitting equation was Y=96.16+2.42 A+0.63 B-3.76 AB-1.57 A2-1.87 B2 ( P<0.01). The optimal extraction process parameters were confirmed to be adding 16 times of water, 64 minutes each time, twice. The deviation rates between the measured values of three verification experiments and the predicted value were 2.00%, 3.23% and 0.66%. Conclusion:The established model of central composite design-response surface methodology has high predictability and the optimized extraction process is stable and feasible.
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Objective:To observe the clinical efficacy of Qigui Tangtongning Granules in the treatment of diabetic peripheral neuropathy (DPN) with qi deficiency and blood stasis.Methods:Prospective cohort study. A total of 80 DPN patients with Qi deficiency and blood stasis in Endocrinology Department of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2021 to May 2022 who met the inclusion criteria were divided into 2 groups by random number table method, with 40 cases in each group. The control group was treated with epalrestat on the basis of routine hypoglycemia, and the treatment group was treated with Qigui Tangtongning Granules on the basis of control group. Both groups were treated for 8 weeks. TCM syndromes were scored before and after treatment. Disease severity was assessed using the Toronto Clinical Scoring System (TCSS). The motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of median nerve and common peroneal nerve were detected by electromyography/induced potentiometer. Serum CRP, TNF-α and IL-6 were detected by ELISA, fasting blood glucose (FPG) and two hours post-meal blood glucose (2 hPG) were detected by automatic biochemical analyzer, and glycosylated hemoglobin (HbA1c) was detected by automatic HBA1C analyzer. Adverse reactions were recorded and clinical efficacy was evaluated.Results:The total effective rate was 95.0% (38/40) in the treatment group and 77.5% (31/40) in the control group, the difference between the two groups was statistically significant ( χ2=5.17, P=0.023). After treatment, the TCM syndrome score and TCSS score of the treatment group were significantly lower than those in the control group ( t=-3.19 and -7.63, P<0.01); Median nerve SNCV [(47.90±4.51) m/s vs. (44.76±3.72) m/s, t=3.40], MNCV [(53.79±3.65) m/s vs. (51.32±4.25) m/s, t=2.79] and common peroneal nerve SNCV [(44.21±2.08) m/s vs. (40.51±2.49) m/s, t=7.23], MNCV [(44.63±4.72) m/s vs. (41.36±4.87) m/s, t=3.05] were significantly higher than those in the control group ( P<0.01); FPG [(5.05±0.63) mmol/L vs. (7.05±1.23) mmol/L, t=-9.17], 2 hPG [(9.10±1.64) mmol/L vs. (12.19±2.61) mmol/L, t=-6.35], HbA1c [(6.79±0.90) % vs. (7.22±1.02) %, t=-2.02] were significantly lower than those in the control group ( P<0.01 or P<0.05); TNF-α [(15.75±5.44) ng/L vs. (32.01±5.33) ng/L, t=-13.51], hs-CRP [(2.58±0.80) mg/L vs. (3.79±1.04) mg/L, t=-5.83], IL-6 [(18.20±4.92) ng/L vs. (29.97±5.18) ng/L, t=-10.41] were significantly lower than those in the control group ( P<0.01). No obvious adverse reactions were observed in 2 groups during treatment. Conclusion:Qigui Tangtongning Granules combined with conventional Western medicine can improve nerve conduction velocity, reduce inflammation and improve clinical efficacy in DPN patients with Qi-deficiency and blood-stasis syndrome.
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Objective To establish the method for the simultaneous determination of hypoxanthine, inosine, guanosine and adenosine in Dilong formula granules by HPLC and compare the fingerprints of Dilong formula granules from different manufacturers by HPLC chromatogram. Methods The contents of hypoxanthine, inosine, guanosine and adenosine were determined by Thermo AcclaimTM120C18 column (4.6 mm×250 mm 5 μm). The mobile phase was acetonitrile-water. Gradient elution with flow rate of 0.6 ml/min was used. Column temperature was 25 ℃. Detection wavelength was 254 nm. 10 batches of samples were tested. The HPLC chromatogram were compared and analyzed by using the similarity Evaluation system of chromatographic fingerprint of traditional Chinese Medicine (version 2012.130723). Results The linear ranges for the detection of hypoxanthine, inosine, guanosine and adenosine showed good linear relationships within their own ranges (r≥0.999 9). The average recoveries were 99.20%~102.98% with RSD of 0.26 %~0.71%. The contents of 4 components in 10 batches of samples were 0.740 0~4.457 4 mg/g, 2.132 3~7.805 0 mg/g, 0.325 4~1.596 1 mg/g, 0.537 2~2.222 9 mg/g respectively. The similarity between HPLC chromatogram and control fingerprints of Dilong formula granules from different manufacturers was greater than 0.91. Conclusion The method could be used to determine the contents of hypoxanthine, inosine, guanosine and adenosine in Dilong formula granule. HPLC fingerprints could be used to evaluation the quality in Dilong formula granule. The similarity of HPLC fingerprints from different manufacturer production of Dilong formula granule is high, but 4 contents in composition are difference.
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OBJECTIVE@#To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.@*METHODS@#A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users).@*RESULTS@#The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study.@*CONCLUSION@#HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).
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ObjectiveTo establish a rat model of hyperuricemia （HUA）， to study the effect of Liqing granules on lowering serum uric acid， and to evaluate its safety . MethodsMale SD rats were randomly divided into solvent control group and model group according to their body weight. For the model group， serum uric acid （SUA） was determined after 7 days of intra-gastric administration of potassium oxyazinate. The model group were randomly divided into model control group， positive control group， and low， medium， high dose group based on SUA level. Each group from the model group continued to receive potassium oxyazinate in the morning. The animals in the model groups received 0.5% CMC-Na， 10 mg·kg-1 benzbromarone （Doses by body weight） and Liqing granules 0.6， 1.2， 2.4 g·kg-1 （Doses by body weight）， respectively in the afternoon. 0.5% CMC-Na suspension with the same volume was given both in the morning and afternoon for the solvent control group. Levels of SUA， creatinine （CREA）， alanine aminotransferase （ALT） and aspartate transaminase （AST） were determined after 32 and 45 days administration of the test substance. ResultsSUA of the model group was （218±23） μmol·L-1 after 7 days of modeling， which was significantly higher than that of the solvent control group （P<0.001）. After 32 days administration of the test substance， SUA didn’t significantly decrease in each dose group （P>0.05）. CREA in the medium and high dose groups significantly decreased （P<0.05）. After 45 days administration of the test substance， SUA in each dose group was significantly decreased （P<0.001）， but CREA， ALT， and AST were not significantly different in each dose group in comparison with the model control group （P>0.05）. ConclusionLiqing granules can assist in lowering blood serum uric acid in the rat HUA model， and no damage to liver and kidney function is found.
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Licorzine granules are common preparations for children zinc deficiency. Considering the long course of treatment, the taste of licorzine granules may become a main factor affecting medication adherence. To date there have been no taste evaluation research into licorzine granules yet. In this study, both sensory evaluation and electronic tongue method were utilized to optimize licorzine granules formulations, evaluate the tastes of licorzine, excipients, optimized formulation in vivo and in vitro. As the results show, bitterness and astringency are the main unpleasant tastes generating from licorzine. Xanthan gum is the main taste-masking excipient, lowering down the bitterness and astringency of licorzine by at least one grade. Good correlation exists between the results of sensory evaluation and electronic tongue method, and an integrated combination of the two helps to obtain objective and rational research conclusions. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.
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OBJECTIVE In order to analyze the current situation of policy tool allocation in China’s TCM formula granule industry， and provide a theoretical basis for the high-quality development of the industry. METHODS Based on the perspective of policy tools，“ TCM formula granules” was used as the keyword to retrieve the official websites of departments directly under the State Council such as the National Medical Products Administration and the National Administration of Traditional Chinese Medicine， as well as provincial governments. The relevant clauses in the policy documents related to TCM formula granules in China from 1993 to 2022 were encoded， and then the application of policy tools was summarized and classified. RESULTS & CONCLUSIONS A total of 12 national documents and 77 provincial documents were ultimately selected， involving 556 relevant policy clauses. It was found that among the relevant policy tools， environmental policy tools had the highest degree of attention， accounting for 62.6%； the proportions of demand-oriented policy tools and supply-oriented policy tools were less， accounting for 17.8% and 19.6%， respectively. From the perspective of policy tools， the use of demand-oriented policy tools in current policy texts was relatively simple， and various policy tools were given low attention； from the perspective of policy objectives， the proportion of use of environmental， demand-oriented and supply-oriented policy tools were not balanced enough. It is suggested to increase the proportion of demand- oriented policy tools to meet international competition； emphasize the use of supply-oriented policy tools to strictly control product quality； consolidate the use of environmental policy tools to standardize quality standards. On this basis， we will coordinate the overall situation， balance the use of various policy tools and promote the development of TCM formula granule industry.
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ObjectiveTo investigate the effect of Qingre Lidan granules in preventing the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy through a retrospective cohort study. MethodsA total of 337 inpatients with choledocholithiasis （including those with cholecystolithiasis at the same time） who underwent laparoscopy combined with choledochoscopic lithotomy in The First Affiliated Hospital of Dalian Medical University from January 1， 2010 to December 31， 2020 were enrolled， and related clinical data were collected. According to the follow－up results， the patients were divided into exposure group （conventional treatment+Qingre Lidan granules） with 225 patients and non－exposure group （conventional treatment） with 112 patients. The recurrence of choledocholithiasis and the administration of Qingre Lidan granules were recorded in detail for both groups. The recurrence rate of choledocholithiasis and the time to recurrence were observed for both groups， and the risk factors for the recurrence of choledocholithiasis were analyzed. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann－Whitney U test was used for comparison of non－normally distributed continuous data between two groups； the chi－square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan－Meier curve was used to estimate the cumulative probability of choledocholithiasis recurrence in the two groups， and the Log－rank test was used for comparison between two groups. ResultsA total of 26 patients experienced the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy， with 12 patients （5.33%） in the exposure group and 14 （12.5%） in the non－exposure group， and the exposure group had a significantly lower recurrence rate than the non－exposure group （χ2=5.394， P=0.020）. The exposure group had a significantly longer mean time to the recurrence of choledocholithiasis than the non－exposure group （40.1±26.7 months vs 19.2±13.5 months， t=2.383， P=0.017）. The Kaplan－Meier curve analysis showed that the non－exposure group had a significantly higher cumulative recurrence rate than the exposure group in different periods of time （P<0.05）. The multivariate logistic regression analysis showed that common bile duct diameter ≥14 mm （odds ratio 〔OR〕=2.935， P=0.031） and multiple calculi （OR=2.911， P=0.029） were independent risk factors for the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopic lithotomy. ConclusionQingre Lidan granules can effectively reduce the recurrence rate of choledocholithiasis and prolong the time to the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy and has a certain clinical effect in preventing the recurrence of choledocholithiasis after surgery.
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Objective:To evaluate the clinical efficacy of Yangxue-Qingnao granule combined with ligustrazine injection in the treatment of wind-phlegm entering collaterals syndrome of cerebral infarction. Methods:A total of 96 patients with cerebral infarction and wind-phlegm entering collaterals syndrome to Suixi County Hospital of Traditional Chinese Medicine from January 2019 to December 2019 were selected and randomly divided into two groups by random number table method, with 48 in each group. The control group was given intravenous ligustrazine injection, and the observation group was given Yangxue-Qingnao granule on the basis of the treatment of the control group. Both groups were treated continuously for 2 weeks. TCM syndrome scores were performed before and after treatment, the National Institutes of Health Stroke Scale (NIHSS) was used to assess the degree of neurological impairment, and the Activity of Daily Living Scale (ADL) was evaluated. To evaluate the patient's quality of life, to detect the high-shear viscosity, low-shear viscosity and plasma viscosity of whole blood with an automatic hemorheology instrument. Results:The total effective rate of the observation group was 95.8% (46/48) and that of the control group was 70.8% (34/48). The difference between the two groups was statistically significant ( χ2=9.08, P<0.01). After treatment, the TCM syndrome score of the observation group was significantly lower than that of the control group ( t=3.51, P<0.01), the NIHSS score was significantly lower than that of the control group ( t=34.41, P<0.001), and the ADL score was significantly higher than that of the control group ( t=57.88, P<0.01). After treatment, the observation group's whole blood high shear viscosity [(5.04 ± 0.93)mPa?s vs. (5.64 ± 1.13)mPa?s, t=2.84], whole blood low shear viscosity [(11.32 ± 1.74)mPa?s vs. (13.39 ± 2.23)mPa?s, t=5.07] and plasma viscosity [(1.51 ± 0.33)mPa?s vs. (1.73 ± 0.47)mPa?s, t=2.65] of the observation group were significantly lower than those in the control group ( P<0.05 or P<0.01). Conclusion:Yangxue-Qingnao granule combined with ligustrazine injection can improve the neurological status and quality of life of patients with cerebral infarction syndrome of wind-phlegm entering the collaterals, and improve the clinical efficacy.
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OBJECTIVE@#To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG).@*METHODS@#This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial.@*RESULTS@#At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P<0.05). But there was no significant difference in post-treatment level of LVEF between the two groups (P>0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P<0.05). Subgroup analysis of the CHFQLS results showed that physiological function, role limitation and vitality were significantly higher in the QTG group than in the TMZ group (15.76±7.85 vs. 7.40±3.36, P<0.05; 16.00±8.35 vs. 10.53±4.64, P<0.05; 15.31±8.09 vs. 7.89±4.60, P<0.05). Compared with TMZ group, treatment with QTG also demonstrated superior performance with respect to 6MWT, CM syndrome, shortness of breath, fatigue, gasping, general edema and NT-proBNP level. No significant adverse reactions or adverse cardiac events occurred during treatment in either group.@*CONCLUSION@#In addition to conventional treatments, the use of QTG as an adjuvant therapy significantly improved cardiac function and QOL in patients with CHF class II or III in stage C. [Registration No. ChiCTR1900022036 (retrospectively registered)].
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Chronic Disease , Double-Blind Method , Heart Failure/drug therapy , Natriuretic Peptide, Brain , Peptide Fragments , Prospective Studies , Quality of Life , Stroke Volume , Ventricular Function, LeftABSTRACT
Objective To investigate the effect of Ganshuang granule combined with entecavir on portal vein thrombosis (PVT) in patients with hepatitis B cirrhosis. Methods A total of 356 patients with hepatitis B cirrhosis who attended and were hospitalized in The Third People's Hospital of Kunming from January 1, 2018 to December 31, 2020 were enrolled and randomly divided into combination group with 191 patients and control group with 165 patients. The patients in the combination group received Ganshuang granule combined with entecavir, and those in the control group received entecavir alone. The course of treatment was at least 24 weeks. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to analyze the cumulative incidence rate of PVT in both groups, and the log-rank test was used for comparison between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for PVT in patients with hepatitis B cirrhosis. Results The 191 patients in the combination group were followed up for 296.25 person-years in total, with a mean follow-up time of 1.55±0.65 years, and there were 8 patients with PVT, with an incidence rate of 4.19% and an incidence density of 1.41 per ten-thousand person-years. The 165 patients in the control group were followed up for 253.25 person-years in total, with a mean follow-up time of 1.53±0.67 years, and there were 20 patients with PVT, with an incidence rate of 12.12% and an incidence density of 4.79 per ten-thousand person-years. There was a significant difference in the incidence rate of PVT between the two groups ( χ 2 =7.687, P =0.006). The cumulative incidence rate of PVT plotted by the Kaplan-Meier method showed that the combination group had a significantly lower cumulative incidence rate of PVT than the control group ( χ 2 =7.226, P =0.007), with a relative risk of 3.155 (95% confidence interval [ CI ]: 1.351-7.370). The univariate Cox analysis showed that hypertension, alanine aminotransferase, aspartate aminotransferase (AST), albumin (Alb), cholinesterase, estimated glomerular filtration rate, alpha-fetoprotein, D-dimer (D-D), Child-Pugh class, and Ganshuang granule combined with entecavir were influencing factors for PVT (all P < 0.05); the multivariate Cox analysis showed that AST (hazard ratio [ HR ]=1.002, 95% CI : 1.000-1.004, P =0.025), and D-D ( HR =1.907, 95% CI : 1.554-2.338, P < 0.001) were independent risk factors for PVT in patients with hepatitis B cirrhosis, while Alb ( HR =0.844, 95% CI : 0.755-0.944, P =0.003) and Ganshuang granule combined with entecavir ( HR =0.350, 95% CI : 0.144-0.851, P =0.021) were independent protective factors against PVT in patients with hepatitis B cirrhosis. Conclusion Ganshuang granule combined with entecavir can significantly reduce the incidence rate of PVT in patients with hepatitis B cirrhosis, thereby exerting a certain preventive effect against PVT.
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The purpose of this study was to systematically analyze the antidepressant mechanism of Chaigui granules from the perspective of biological metabolic network by using integrated metabolomics and biological network analysis tools. The model of chronic unpredictable mild stress (CUMS) depression rat was established, and LC-MS-based plasma metabolomics was used to identify the key metabolites and analyze metabolic pathways underlying the antidepressant effects of Chaigui Granules. The key metabolites regulated by Chaigui granules was integrated with biological network analysis tools to further focus on the key metabolic pathways and explore the potential targets of the antidepressant effect of Chaigui granules. The results showed that there were significant differences in the plasma levels of 20 metabolites in the model group compared with the control group (P < 0.05), Chaigui granules significantly regulated 12 metabolites including docosatrienoic acid, 3-hydroxybutyric acid, 4-hydroxybenzaldehyde, chenodeoxycholic acid, cholic acid, L-glutamine, glycocholic acid, linoleyl carnitine, L-tyrosine, N-acetylvaline, palmitoylcarnitine, arachidonic acid. Further network analysis of the key metabolites regulated by Chaigui granules indicated that plasma arachidonic acid metabolism might be the core pathway for the antidepressant effect of Chaigui granules, with 10 proteins were potential targets for the antidepressant effect of Chaigui granules, including CYP2B6, CYP2E1, CYP2C9, CYP2C8, PLA2G6, PTGS2, ALOX15B, PTGS1, ALOX12 and ALOX5. The animal experimental operations involved in this paper was followed the regulations of the Animal Ethics Committee of Shanxi University and passed the animal experimental ethical review (Approval No. SXULL2020028).
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OBJECTIVE To study the effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute myocardial infarction. METHODS The model of heart failure after acute myocardial infarction was established by ligaturing the anterior descending branch of the left coronary artery in rats. The model rats were divided into model group，Shenfu yixin granule low-dose and high-dose groups （1.76，8.8 g/kg），Fosinopril sodium tablets group （positive control ，4 mg/kg），sham operation group was set up （only threading without ligation at the same position ），with 8 rats in each group. After 4 weeks of drug intervention ，the hemodynamic indexes of rats in each group were measured by physiological recorder. The pathological changes of myocardial tissue were observed in each group. The level of oxidative stress in cardiomyocytes ， mitochondrial membrane potential ，protein expression of PTEN-induced putative kinase 1（PINK1），E3 ubiquitin ligase Parkin and ubiquitin binding protein P 62 in myocardial tissue of rats in each group were detected. RESULTS Compared with sham operation group ，the pathological injuries such as myocardial fiber morphology disorder and inflammatory cell infiltration were serious. The left ventricular end systolic pressure （LVESP），maximum rate of rise of left ventricular internal pressure （+dp/dtmax）， maximun rate of decrease of left ventricular internal pressure （－dp/dtmax），total antioxidant capacity ，mitochondrial membrane potential，PINK1，Parkin and P 62 protein expression were significantly decreased in model group （P＜0.01）. The left ventricular end diastolic pressure （LVEDP），the level of reactive oxygen species and the activity of reduced nicotinamide adenine dinucleotide phosphate in left ventricular ischemic cardiomyocytes were significantly increased （P＜0.01）. Compared with model group ，the pathological injuries of myocardial tissue in intervention groups were alleviated ，and above indexes were improved in varying degrees（P＜0.01 or P＜0.05）. CONCLUSIONS Shenfu y ixin granule can reduce the level of oxidative stress and alleviate heart failure after acute myocardial infarction ，which may be related to the activation of Parkin-dependent pathway to strengthen mitochondrial autophagy and reduce mitochondrial dysfunction.
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OBJECTIVE To study the impr ovement effects of Dianxianqing granule on blood-brain barrier （BBB）injury in Alzheimer’s disease （AD）model mice by regulating NLR family pyrin domain containing 3（NLRP3）inflammasome signaling pathway. METHODS Totally 125 mice were randomly divided into sham operation group （n＝25）and modeling group （n＝100） by body weight. AD model was induced by intracerebroventricular injection of β-amyloid 25-35 in model group. Sham operation group was given normal saline with same method. The 100 model mice were randomly divided into model group ，Donepezil hydrochloride tablets group （positive control 1，1.3 mg/kg，i.g.），MCC950 group [positive control 2（selective NLRP 3 inhibitor），10 mg/kg，i.p.] and Dianxianqing granule group （12.48 g/kg by crude drug ，i.g.）by body weight ，with 25 mice in each group. Second day after modeling ，administration groups were given relevant medicine ，once a day ，for consecutive 21 d. Sham operation group and model group were given intragastric administration of water and intraperitoneal injection of normal saline. At last administration，the learning and memory ability was determined by Y maze test ，and blood-brain barrier permeability was measured by Evans blue leakage assay. The expressions of NLRP 3，anti-ionized calcium-binding adapter molecule 1（IBA-1），nuclear factor kappa B （NF-κB）p65，p53 upregulated modulator of apoptosis （PUMA），occludin（ocln），zonula occluden- 1（ZO-1）and claudin-5 （cldn5） in cerebral tissue were determined. RESULTS Compared with model group ， spontaneous alternate response rate ，protein expressions of ocln ，cldn5 lnzyxyqy2003@163.com and ZO- 1 in cerebral tissue were increased significantly in administration groups （P＜0.05 or P＜0.01）；Evans blue E-mail：jiadg2003@126.com content and protein expressions of NLRP 3，IBA-1，PUMA and NF-κB p65 in cerebral tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granule can improve BBB injury of AD model m ice by inhibiting NLRP 3 inflammasome signaling pathway.
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As one of the "Three Drugs Three Prescriptions" anti-COVID-19 traditional Chinese medicine, Jinhua Qinggan granules (JHQG) has been proved to have clear clinical effects. With complex medicinal flavors and ingredients, there is no systematic research report on chemical composition in vivo or in vitro. An ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) method was developed in this study to identify the components of the anti-COVID-19 traditional Chinese medicine JHQG granules. Analyze the collected rat plasma samples after administration and explore the exposed components in rats within 8 hours after intragastric administration. Preliminary pharmacokinetic analysis was then performed on this basis. Through UPLC-QTOF/MS analysis and verification by standard products, a total of 77 chemical components in JHQG formula have been identified, among which 22 compounds were highly exposed in vivo, mainly derived from three medicinal materials of honeysuckle, scutellaria and forsythia. Through the assessment of the blood drug concentration by the compartment model, 6 PK parameters of 4 high-exposure chemical components have been obtained, clarifying the metabolic characteristics of the main exposed components in JHQG briefly. The method is simple, efficient, sensitive and accurate and provides research basis to the clarification of the pharmacodynamics material basis and mechanism of JHQG, which has certain reference significance for the basics and applications research of the traditional Chinese medicine prescriptions in fighting the SARS-CoV-2.
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Abstract The purpose of this study is to optimize the composition of extragranular excipients (EGE) and mixing time of granules with EGE of paracetamol tablet formulation using Design of Experiments (DoE) approach. The effect of the composition of EGE and the mixing time of granules with EGE on granule and tableting properties of paracetamol tablet formulation was investigated using a combined model of mixture and process factors (Design-Expert 12). A total of 18 tablet formulations were manufactured by wet granulation using varying compositions of EGE and varying mixing time. Granule and tablet properties of each formulation were evaluated as response variables for the design, data generated were fitted into models and analysed to generate a design space that was used for optimization studies. The proposed EGE composition as predicted by the design was confirmed and validated after preparation and evaluation of the granule and tablet properties. The optimized composition for the EGE that yielded granules and tablets of desirable characteristics was found to be maize starch (5 %), talc (4.9 %) and magnesium stearate (0.1 %) with a mixing time of 2 min. The tablets produced with the optimized composition had better mechanical strength and disintegration time than the formulation prepared using an existing formula of maize starch (7.8 %), talc (2 %) and magnesium stearate (0.2 %) that were obtained using the One Variable at a Time (OVAT) approach. This study confirmed the relevance of quality by design in development of pharmaceutical formulations.
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Objective:To study the HPLC fingerprints of Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules and the differences of active ingredients in different proportions; To explore the content changes of key components in different proportions of Coptidis Rhizoma- Magnoliae Officmalis Cortex. Methods:HPLC was used to determine the contents of several alkaloids and total phenol of Magnolia officinalis in Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules and their fingerprints, and the similarity evaluation, cluster analysis and principal component analysis were performed. Results:The similarity of fingerprint of 10 batches of Coptidis Rhizoma- Magnoliae Officmalis Cortex was > 0.950. 17 common peaks were identified, and 6 components were identified. Compared with single medicine, the contents of alkaloids and total phenols in the Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules were significantly reduced. The contents of multiple alkaloids and total phenols in the Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules in different proportions were different, and the contents of alkaloids and total phenols were the highest when the proportion of Coptidis Rhizoma- Magnoliae Officmalis Cortex was 2∶1. Conclusion:The contents of main components of Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules with different proportions are different, which can provide a certain basis for studying the compatibility mechanism of TCM couplet medicines.