This study was designed to validate the correlation between integrated pharmacokinetic and therapeutic effects of alkaloids using bile processed Rhizoma Coptidis (BRC). Rats were divided into three groups: normal, disease model, model+BRC. Rats were induced to have an excessive heat syndrome. Rectal temperatures were collected at 0, 3, 6 and 9 h after single oral administration of the drugs. The plasma concentrations of three alkaloids were quantified at different times by UPLC-MS/MS after the administration of BRC. An approach of self-defined weighting coefficiency was created to the holistic pharmacokinetic profiles of alkaloids in BRC. The classified and integrated synthetic concentrations were obtained, and then the pharmacokinetic parameters of alkaloids were calculated from non-compartmental model analysis. The potential relationship between the integrated mean concentration of alkaloids and the antifebrile efficacy was investigated. The holistic t(max) of alkaloids was 1.11 h, the antifebrile effect of BRC at 3 h was improved over the model group. Double peaking appeared in the integrated blood concentration-time curve, the second t(max) of alkaloids was 4.82 h. The antifebrile effects of BRC at 3-6 h were significant, and the antifebrile effects at 6-9 h was decreased significantly. Dynamic variation of alkaloids of BRC in the body exhibited the similarity to the pattern of its antifebrile effect.
Administration, Oral ; Alkaloids ; pharmacokinetics ; Animals ; Bile ; Coptis ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Tandem Mass Spectrometry

Adolescent ; Adult ; Female ; Hearing Loss, Sudden ; etiology ; psychology ; Humans ; Male ; Middle Aged ; Young Adult

Toad venom is the Bufo bufo gargarizans or B. melanostictus after the ears of the gland secretion, used in the treatment of various cancers in recent years. Research shows that the main anti-tumor components in bufadienolide. Bufadienolide have free type structure and conjunct type structure. To identify and clarify the difference between bufogenin and bufotoxin contained in Bufonis Venenum, which was from B. bufo gargarizans, an UPLC-TQ-MS method has been established. UPLC-TQ-MS method was used to identify and quantify the major bufadienolides in Bufonis Venenum. UPLC-TQ-MS assay with positive ion mode was performed on a Waters ACQUITY UPLC BEH C, (2.1 mm x 100 mm, 1.7 µm) with the mobile phase consisting of 0. 1% aqueous formic and acidacetonitrile in gradient elution at a flow rate of 0.4 mL · min⁻¹ and the column temperature was set at 35 °C. By comparing their retention time and high resolution mass data of Bufonis Venenum extracts, 37 effective components were primarily identified by MS/MS analysis in positive ion mode. Twenty-six of them were free-type bufadienolides (bufogenin), 11 of them were conjugated bufadienolides. There were significant differences in the main composition between fresh and processed Bufonis Venenum. The study found that the chemical composition of toad venom through great changes after processing, conjunct type content is much less, free type content as well change.
Amphibian Venoms ; chemistry ; metabolism ; Animals ; Bufonidae ; classification ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Molecular Structure ; Tandem Mass Spectrometry ; methods

Objective To compare the effects of biphasic square waveform (BSW) with low or high energy on external defibrillation.Method Adult swine model of closed chest ventricular fibrillation induced by electricity was established.Eighteen swine,weighing (30?3.3) kg were randomly divided into three groups:50-50-50 J group (n=6),30-50-75 J group (n=6),120-150-200 J (n=6).After three minutes of ventricular fibrillation without treatment,the pigs in the three groups were defibrillated accordance to the above sequences. Results 30 J BSW didn't succed to external defibrillate.The first defibrillation successful rate of 50 J and 120 J BSW was 5/6.The total defibrillation successful rate of every group was 100%.All pigs quickly had spontaneous circulation after defibrillation and survived more than 24 hours.ST-T change of low-energy was less than that of high-energy.After resuscitation,myocardial function decreased,but there had not significant differences between groups.Conclusions In the study,30J BSW could not reach successful defibrillation,and 50 J and 120 J BSW had similar defibrillation efficacy.The ideal energy of BSW external defibrillation was 50 J.

Abstract: Objective To explore the influencing factors of serum HBeAg loss in patients with chronic hepatitis B (CHB) and and provide evidence for effective treatment of CHB. Methods A follow-up cohort of HBeAg-positive CHB patients was established in the the Infectious Diseases Outpatient Clinic of hospital. Regular follow-up and laboratory test indicators were collected to analyze the changes of serum HBeAg in HBeAg-positive CHB patients during the follow-up period. The subjects were divided into the case group (serum HBeAg loss) and the control group (serum HBeAg not loss) according to whether serum HBeAg loss occurred. The baseline data characteristics of the two groups were analyzed and compared, and the influencing factors of serum HBeAg loss were analyzed by Cox univariate and multivariate regression. Results A total of 634 HBeAg-positive CHB patients were enrolled, with a total follow-up of 2 570.01 person-years. Among them, 237 cases of serum HBeAg loss occurred, with the mean follow-up time of 40.92 months, and the rate of HBeAg loss was 9.22/100 person-years. There were significant differences in HBV family history, antiviral therapy, baseline WBC, PLT, ALT, AST, T˗Bil, GGT, AFP, quantitative HBsAg and quantitative HBeAg between serum HBeAg loss group and serum HBeAg not loss group (P<0.05). Cox regression analysis showed that family history of HBV (HR 0.68, 95％CI:0.50-0.92, P=0.012), ALT (HR2.06, 95％CI:1.52-2.79, P<0.001), quantitative HBsAg (HR 0.68, 95％CI:0.48-0.95, P=0.024), quantitative HBeAg (HR 0.48, 95％CI:0.31-0.74, P=0.001) were independent influencing factors for HBeAg loss in HBeAg-positive CHB patients. Conclusions HBeAg-positive CHB patients without family history of HBV, initial ALT≥80 U/L, quantitative HBsAg<1 000 IU/ml, quantitative HBeAg<1 000 C.O.I are more likely to have serum HBeAg loss.

Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.

This experiment was expected to test whether nitric oxide (NO) exerted significant effect on the central respiratory rhythm. Experiments were performed on in vitro brainstem slice preparations from neonatal rats. These preparations include the medial region of the nucleus retrofacialis (mNRF); a part of pre-Bötinger complex, ventral respiratory group (VRG) and dorsal respiratory group (DRG). Respiratory-related burst activities were recorded from hypoglossal nerve rootlets before and during superfusion of the slice preparation with L-Arginine (L-Arg), sodium nitroprusside (SNP) or 7-nitro indazole (7-NI, an inhibitor of NO synthase). After perfusion with L-Arg and SNP, there was no significant change in respiratory rhythmical discharge activity (RRDA), but 7-NI decreased the integral amplitude of burst and inspiratory time. These results indicate that NO may take part in the inspiratory off-switching mechanism and that it also modulates the amplitude of respiratory-related bursts.
Animals ; Animals, Newborn ; Arginine ; pharmacology ; Brain Stem ; physiology ; Electrophysiology ; Indazoles ; Neurons ; physiology ; Nitric Oxide ; physiology ; Nitric Oxide Synthase ; antagonists & inhibitors ; Nitroprusside ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Respiration ; Respiratory Center ; physiology

Objective To conclude nursing experience of full series artificial liver support system in the treatment of acute fatty liver in pregnancy. Methods Development of artificial liver support system according to patient's condition, total continuous renal replacement therapy 7days, double plasma molecular absorb system 3 times, plasma replacement 3 times, molecular adsorbent circulation system 2 times. Results After treatment, the patient was discharged after 20 days in hospital. Conclusions The full range of artificial liver support system can effectively treat the patients with acute fatty liver in pregnancy, it will greatly reduce the mortality of patients with acute fatty liver in pregnancy.

Objective: To observe the efficacy of electroacupuncture (EA) plus Yi Jin Jing (Sinew-transforming Qigong Exercises) for knee osteoarthritis (KOA). Methods: A total of 60 patients with KOA were divided into an observation group and a control group according to the random number table method, with 30 cases in each group. Patients in the observation group received the treatment of EA plus Yi Jin Jing (Sinew-transforming Qigong Exercises), while patients in the control group only received EA treatment. Both groups were treated for 5 weeks. The changes of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores in the two groups were observed after treatment. Results: After treatment, the total effective rate in the observation group (92.3％) was significantly higher than that in the control group (70.0％), (P<0.05); the WOMAC and VAS scores in both groups were significantly lower than those before treatment, showing statistical significance (all P<0.01); there were significant differences in the post-treatment changes in the WOMAC and VAS scores between the two groups (P<0.05, P<0.01). Conclusion: EA plus Yi Jin Jing (Sinew-transforming Qigong Exercises) is clinically effective for KOA. This combined treatment can alleviate clinical symptoms.

Objective To explore the biological functions of retinoic acid-inducible gene-I(RIG-I) in vivo through phenotype analysis of RIG-I knockout mice. Methods The gene expression of RIG-Ⅰ in various tissues of mice was examined with Northern blotting and semi-quantitative RT-PCR.The phenotypes observed included body weight measurement,differential count of peripheral blood cells,metabolic parameters measurement and histopathologic examination. ResultsRIG-Ⅰ expressed in various tissues of mice with different levels.No gross developmental abnormalities and expected maturation arrest in granulocytic differentiation were observed in RIG-Ⅰ knockout mice.However,RIG-Ⅰ knockout mice exhibited an unexpected increase in the ratios of neutrophiles to lymphocytes in peripheral blood and increased susceptibility to bacteria infection. Conclusion RIG-Ⅰ may play an important role in immune regulation in mice.