Objective:To discuss the effect of Fuzheng Ruanjian Anticancer Formula on the malignant biological behaviors of the hepatocellular carcinoma HepG2 cells by requlating protein kinase B(Akt)/murine double minute 2(MDM2)/P53 signaling pathway.Methods:The HepG2 cells were treated with 0,0.05,0.10,0.20,0.40,0.80,1.60,3.20,and 6.40 g·mL-1 Fuzheng Ruanjian Anticancer Formula for 48 h.CCK-8 method was used to detect the survival rates of the HepG2 cells in various groups,and the concentrations of Fuzheng Ruanjian Anticancer Formula for the subsequent experiments were screened.The HepG2 cells were divided into control group,low dose of Fuzheng Ruanjian Anticancer Formula group(0.2 g·mL-1),medium dose of Fuzheng Ruanjian Anticancer Formula group(0.4 g·mL-1),high dose of Fuzheng Ruanjian Anticancer Formula group(0.8 g·mL-1),SC79 group(8 mg·L-1 SC79),and high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group(0.8 g·mL-1 Fuzheng Ruijian Anticancer Formula+8 mg·L-1 SC79).CCK-8 method was used to detect the proliferation activities of the HepG2 cells in various groups;clone formation assay was used to detect the clone formation rates of the HepG2 cells in various groups;flow cytometry was used to detect the apoptotic rates of the HepG2 cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion HepG2 cells in various groups;Western blotting method was used to detect the expression levels of proliferating cell nuclear antigen(PCNA),cysteine aspartate specific proteinase(Caspase-3),matrix metalloproteinase(MMP)-2,MMP-9,phosphorylated Akt(p-Akt),phosphorylated MDM2(p-MDM2),and P53 proteins in the HepG2 cells in various groups.Results:As the increasing of concentrations of Fuzheng Ruanjian Anticancer Formula(0,0.05,0.10,0.20,0.40,0.80,1.60,3.20,and 6.40 g·mL-1),the surival rates of the HepG2 cells were gradually decreased(P<0.05),and 0.2,0.4,and 0.8 g·mL-1 Fuzheng Ruanjian Anticancer Formula were selected for the subsequent experiments.The CCK-8 assay results showed that compared with control group,the proliferation activities of the HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05),in a dose-dependent manner,while the proliferation activity of the cells in SC79 group was significantly increased(P<0.05).Compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the proliferation activity of the HepG2 cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly increased(P<0.05).The clone formation assay results showed that compared with control group,the clone formation rates of the HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the clone formation rate of the cells in SC79 group was significantly increased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the clone formation rate of the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly increased(P<0.05).The flow cytometry results showed that compared with control group,the apoptotic rates of the HepG2 cells in low,medium,and high doses of Fuzheng Ruijian Anticancer Formula groups were significantly increased(P<0.05)in a dose-dependent manner,while the apoptotic rate of the cells in SC79 group was significantly decreased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the apoptotic rate of the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the numbers of migration and invasion cells in SC79 group were significantly increased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the numbers of migration and invasion HepG2 cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the expression levels of Caspase-3 and P53 proteins were significantly increased(P<0.05)in a dose-dependent manner,while the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in SC79 group were significantly increased(P<0.05),and the expression levels of Caspase-3 and P53 proteins were significantly decreased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group were significantly increased(P<0.05),while the expression levels of Caspase-3 and P53 proteins were significantly decreased(P<0.05).Conclusion:Fuzheng Ruanjian Anticancer Formula may inhibit the proliferation,migration,and invasion of the HepG2 cells and promote the apoptosis,and its mechanism may be related to suppressing the Akt/MDM2 signaling pathway and upregulating the P53 proteim expression.

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.
Rats ; Animals ; 1-Naphthylisothiocyanate/toxicity* ; Powders ; NF-E2-Related Factor 2/genetics* ; Rats, Sprague-Dawley ; Cholestasis, Intrahepatic/drug therapy* ; Liver ; Superoxide Dismutase ; Oxidative Stress

Objective: To explore the effect of Chaishao Shugan Lidan Paishitang on inflammation, stress response and gastrointestinal function in gallstones patients with chronic cholecystitis. Method: Gallstones patients with chronic cholecystitis treated in our hospital from March 2017 to May 2018 were randomly divided into two groups, with 65 cases in each group. The control group was orally given ursodeoxycholic acid combined with metronidazole. In addition to the therapy of the control group, the Observation group was also given Chaishao Shugan Lidan Paishitang. Traditional Chinese medicine symptom scores, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitive C-reactive protein (hs-CRP), superoxide disproportionation alcohol (SOD), propylene glycol (MDA) and carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), gastric dynamic element (MOT), gastrin-releasing (GAS) and somatostatin (SS), alanine aminotransferase (ALT), aspertate aminotransferase (AST), total bilirubin (TBIL) and total bile acid (associates), and total cholesterol (TC) levels before and after treatment were observed in two groups, and the curative effect, reactions and relapse were also observed. Result: The inflammatory effect, stone ablation effect and clinical effect of observation group were significantly better than those of control group (Z=2.329, P<0.05; Z=2.686, P<0.05; Z=2.940, P<0.05). The scores of right upper abdominal dull pain, abdominal distension, nausea and vomiting, and pale red tongue in the observation group after treatment were lower than those in control group (P<0.05). The levels of ALT, AST, TC, TNF-α, hs-CRP, IL-6, CEA, CA19-9, SS and MDA in observation group were lower than those in control group (P<0.05), while the levels of MOT, GAS and SOD in the observation group were higher than those in control group (P<0.05). The recurrence rates of observation group and control group were 3.17%(2/63) and 14.29%(9/63), respectively, with statistically significant difference between two groups (χ²=5.140, P<0.05). Conclusion: The treatment of gallstones patients with chronic cholecystitis by Chaishao Shugan Lidan Paishitang has a good curative effect, and can alleviate clinical symptoms, inhibit oxidative stress and inflammation, improve liver and bile functions and gastrointestinal function, and reduce the recurrence rate.

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) μmol·L-1.
Broussonetia ; chemistry ; Chromatography, High Pressure Liquid ; Flavonoids ; isolation & purification ; pharmacology ; Magnetic Resonance Spectroscopy ; Phytochemicals ; isolation & purification ; pharmacology ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors

The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.
Animals ; Atherosclerosis ; drug therapy ; Carotid Arteries ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Nitric Oxide Synthase Type III ; metabolism ; Oxidative Stress ; Rabbits ; Random Allocation ; Signal Transduction ; drug effects

BACKGROUNDFemale sexual dysfunction (FSD) is a highly prevalent and often underestimated problem. However, large-scale, population-based epidemiological surveys of FSD are scarce in China. The present study was conducted to evaluate the prevalence and the potential risk factors of FSD across a selection of social groups in Beijing, China, based on the Female Sexual Function Index (FSFI).

METHODSA cross-sectional study based on the multiple-stage cluster sampling was performed with adult women throughout the Dongcheng and Shunyi districts of Beijing. The Chinese version of FSFI was used, as well as questions on demographic characteristics, the disease-related context, and social relationships.

RESULTSA total of 6000 consecutive women entered this study, with an actual response from 5024 women, corresponding to a response rate of 83.7%. A total of 4697 (78.3%) questionnaires were effective. The prevalence of adult FSD in Beijing was 2973 (63.3%) using a score of 26.55 as the boundary value, whereas the total mean FSFI score was 23.92 ± 6.37. However, 1423 (30.3%) women did not seek help. By multivariate logistic regression analysis, the possible potential risk factors included age (odds ratio [OR] = 1.051), dissatisfaction with the spouse's sexual ability (OR = 3.520), poor marital affection (OR = 2.087), spouse sexual difficulties (OR = 1.720), dissatisfaction with married life (OR = 1.476), living in a rural area (OR = 1.292), chronic pelvic pain (OR = 1.261), chronic disease (OR = 1.534), previous pelvic surgery (OR = 1.605), vaginal delivery (OR = 2.285), lower education (OR = 3.449) and postmenopausal (OR = 3.183).

CONCLUSIONSAs suggested by the FSFI scores, female sexual problems are highly prevalent in Beijing. Dissatisfaction with the spouse's sexual ability, poor marital affection, sexual difficulties of the spouse, dissatisfaction with the marriage, rural life, CPP, and postmenopausal were conceivable risk factors for FSD in Beijing women.

OBJECTIVETo investigate the significance of flexible bronchoscopy in children with respiratory diseases.

METHODSA retrospective analysis was performed for the clinical data of 80 children who were hospitalized due to respiratory diseases (including severe pneumonia, Mycoplasma pneumoniae pneumonia with atelectasis/lung consolidation/local emphysema, protracted pneumonia, coughing and wheezing of unknown cause, chronic cough of unknown cause, and laryngeal stridor) and who underwent flexible bronchoscopy/alveolar lavage.

RESULTSBronchoscopy found that all the 80 children had endobronchial inflammation, among whom 28 children had severe airway obstruction by secretion. Twenty-four children had congenital airway dysplasia besides endobronchial inflammation, and three children had bronchial foreign bodies. In the children with coughing and wheezing of unknown cause and laryngeal stridor, some had congenital airway dysplasia or bronchial foreign bodies. Among the 27 children with Mycoplasma pneumoniae pneumonia, 26 had severe airway obstruction/embolization by secretion; 25 children (93%) underwent chest imaging again at 2 weeks after alveolar lavage, and the results showed complete or partial lung recruitment. Among the 80 children who underwent bronchoscopy, 3 had severe hypoxemia during surgery, 1 had epistaxis, 1 had minor bleeding during alveolar lavage, 3 had transient bronchospasm, and 5 had postoperative fever; these children were all improved after symptomatic treatment.

CONCLUSIONSFlexible bronchoscopy is safe and reliable in children with respiratory diseases. Early alveolar lavage under a flexible bronchoscope is recommended for children with severe/refractory Mycoplasma pneumoniae pneumonia to improve prognosis. Flexible bronchoscopy is recommended for children with recurrent coughing and wheezing and persistent laryngeal stridor, in order to directly observe the throat and airway under an endoscope.

Bronchoscopy ; adverse effects ; methods ; Child ; Child, Preschool ; Cough ; diagnosis ; Female ; Humans ; Infant ; Lung Diseases ; diagnosis ; Male ; Pneumonia, Mycoplasma ; diagnosis ; Respiratory Sounds ; diagnosis ; Retrospective Studies

Objective To explore the interaction of sleep quality and depression among patients with type 2 diabetes. Methods With multistage cluster sampling, all the participants were interviewed with self-designed questionnaire, diabetes-specific quality of life scale and self-rating depression scale, and Pittsburgh sleep quality index scale. Chi-square test was used for qualitative data. Risk factors were analyzed by means of multiple linear regression or logistic regression model. The indicator of interaction was calculated according to the delta method. Results There were 944 residents involved in the final analysis, including 365 males and 579 females. The average age was (64. 0 ± 10. 2) years. Compared with patients with type 2 diabetes mellitus( T2DM) who had good sleep quality and no depression symptoms, the risk of quality of life in those with good sleep quality but depression was 2. 75 (95% CI 1. 59-4. 77); and the risk of quality of life in those with poor sleep quality and no depression was 1. 55(95%CI 1. 03-2. 33). The risk of quality of life in those with poor sleep quality and depression was 4. 97(95% CI 2. 34-9. 63). Due to poor sleep quality and depression in patients with T2DM the combined interaction index was 2. 48 (95% CI 1. 44-4. 29), the relative excess risk was 3. 42(95% CI 2. 16-4. 67), and the attributable proportion was 0. 51(95% CI 0. 32-0. 70). Conclusion A combined interaction of poor sleep quality and depression in affecting the quality of life was found in type 2 diabetic patients. When both factors existed at the same time, the interaction effect of these 2 factors was greater than the single one.

Objective To measure the diameter of cochlear nerve(CN) in normal hearing children with different ages,and evaluate the diameter variations with age.Methods A total of 156 normal-hearing children were assessed with 3D-FIESTA sequence scanning of the inner ear.All the subjects were divided into 13 groups according to age,witha group of ≤6 months,a group of ≤1 year,and 11 groups from one year to 12 years.Each group had 12 cases,including 6 boys and 6 girls.The diameter of CN was measured at the entrance of the cochlea,the middle of internal auditory canal(IAC) and the fundus of IAC respectively on the axial and oblique sagittal images of 3.0 T MRI by two independent observers.The average values measured by them were the final results.The intraclass correlation coefficient was used to determine the consistency between the two independent observers.The t test was used to access differencesin CN diameter by sex and sides.One-way analysis of variance(ANOVA) and two-way ANOVA were used for comparisons among different groups.Spearman correlation coefficient was applied to find a correlation between the CN diameter and age.Results The diameters of normal-hearing children's CN at the middle of the IAC,IAC fundus and the entrance of the cochlea were (1.12 ± 0.08),(1.05 ± 0.06),(0.87 ± 0.14) mm respectively,and there was significant difference among the three measuring points (F=527.57,P＜0.05).The diameters of the CN had no significant differenc (P＞0.05) in age-groups,gender and sides(P＞0.05),and there was no correlation between the diameters of normal children's CN and age.Conclusions The diameters of normal-hearing children's CN change with different points of the IAC,of which the maximum value is at the middle of the IAC,followed by the IAC fundus,and the entrance of the cochlea is at the minimum,more over the normal size doesn't change with age.

Veregen™ and Fulyzaq are the first two botanical drug products that were approved by the Food and Drug Administration (FDA) to market in the US in recent years. Additional herbal medicines, including Compound Danshen Dripping Pills, Fuzheng Huayu Tablets, Xuezhikang Capsule, Guizhi Fuling Capsule, Kanglaite Capsule and Kanglaite Injection, have filed the investigational new drug (IND) application to the FDA and are in phase II or phase III clinical development. In order to gain better understanding of the process of botanical drug approval in the US, this article examines the aforementioned drugs by looking at their composition, indication, prior clinical experience and clinical development process, and summarizes key features that enabled IND filing and marketing approval by the FDA.
China ; Drug Approval ; legislation & jurisprudence ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Nonprescription Drugs ; therapeutic use ; United States ; United States Food and Drug Administration