21- versus 25-mm Circular Staplers for Cervical Anastomosis: A Propensity-Matched Study.

BACKGROUND: The use of a small circular stapler (CS) has been reported to increase the incidence of benign anastomotic stricture of the intrathoracic anastomosis after esophagectomy, but no study has evaluated the effects of the CS size on cervical esophagogastrostomy. Based on a propensity-matched comparison, the present study was designed to determine whether the perioperative outcomes differ between 21- and 25-mm CSs after minimally invasive esophagectomy with cervical anastomosis. METHODS: From January 2015 to December 2017, 162 patients who received CS cervical esophagogastric anastomosis after minimally invasive esophagectomy for esophageal cancer were identified from our surgical database. A propensity-matched analysis was used to compare the outcomes between the 21- and 25-mm CS groups. Endpoints included anastomotic leak, dysphagia, reflux, stricture, and other major postoperative outcomes within 6 postoperative months. RESULTS: There were 69 and 93 patients in the 21- and 25-mm CS groups, respectively. Propensity matching produced 57 patients in each group. The two groups were not remarkably different in benign anastomotic stricture rate (P = 0.528). All strictures were resolved by balloon dilatation. The 25-mm CS group had a significantly longer operative time in cervical anastomosis than the 21-mm group (P = 0.005). No statistically significant differences in anastomotic leak rates, dysphagia scores, reflux scores, or other postoperative complications were noted between the two groups. CONCLUSIONS: The use of a 21-mm CS in minimally invasive esophagectomy with cervical esophagogastric anastomosis did not result in greater anastomotic stricture as compared with a 25-mm CS. The 21-mm CS was associated with a significantly shorter operative time.

Therapeutic Efficacy and Safety of Paeoniae Radix Rubra Formulae in Relieving Hyperbilirubinemia Induced by Viral Hepatitis: A Meta-Analysis.

OBJECTIVE: Hyperbilirubinemia is one of the most devastating pathologies induced by various liver diseases. Formulae related to Paeoniae Radix Rubra (PRR) at high doses have been applied to treat hyperbilirubinemia in traditional Chinese medicine (TCM). The aim of this systematic review and meta-analysis is to assess the efficacy and safety of formulae relevant to high-dose PRR in patients suffering from hyperbilirubinemia induced by viral hepatitis. METHODS: We performed a meta-analysis of randomized-controlled clinical trials to evaluate the efficacy and safety of formulae that apply a high dose of PRR for hyperbilirubinemia. Seven databases were searched until April, 2015. All studies were included according to detailed criteria and assessed for methodological quality. The outcome measurements were recorded for further analysis using the RevMan 5.2.11 software. RESULTS: Fifteen articles involving 1323 patients with hyperbilirubinemia were included. Formulae with high-dose PRR might promote the efficacy of either a combined application ([OR: 3.98, 95% CI (2.91, 5.43)]; P < 0.01) or a single application ([OR: 4.00, 95% CI (1.50, 10.68)]; P < 0.01) for hyperbilirubinemia. The indices of TBIL, ALT, and AST significantly decreased ([MD: -75.57, 95% CI (-94.88, -56.26)], [MD: -26.54, 95% CI (-36.19, -16.88)], and ([MD: -28.94, 95% CI (-46.26, -11.61)]; P < 0.01), respectively. In addition, formulae with high-dose PRR could enhance the treatment efficacy of hyperbilirubinemia triggered by hepatitis B ([OR: 2.98, 95% CI (1.75, 5.05)]; P < 0.01). Furthermore, the efficacy was enhanced with an increasing dosage of PRR. Two articles reported that no side effects occurred in clinical trials, and three studies noted that patients presented light digestive tract symptoms. CONCLUSION: Formulae relevant to high-dose PRR ameliorate hyperbilirubinemia and might constitute a promising therapeutic approach. For widespread acceptance by practitioners, more rigorously designed multicenter, double-blind, randomized, and large-scale controlled trials are required.

Establishment of a bioassay for the toxicity evaluation and quality control of Aconitum herbs.

Currently, no bioassay is available for evaluating the toxicity of Aconitum herbs, which are well known for their lethal cardiotoxicity and neurotoxicity. In this study, we established a bioassay to evaluate the toxicity of Aconitum herbs. Test sample and standard solutions were administered to rats by intravenous infusion to determine their minimum lethal doses (MLD). Toxic potency was calculated by comparing the MLD. The experimental conditions of the method were optimized and standardized to ensure the precision and reliability of the bioassay. The application of the standardized bioassay was then tested by analyzing 18 samples of Aconitum herbs. Additionally, three major toxic alkaloids (aconitine, mesaconitine, and hypaconitine) in Aconitum herbs were analyzed using a liquid chromatographic method, which is the current method of choice for evaluating the toxicity of Aconitum herbs. We found that for all Aconitum herbs, the total toxicity of the extract was greater than the toxicity of the three alkaloids. Therefore, these three alkaloids failed to account for the total toxicity of Aconitum herbs. Compared with individual chemical analysis methods, the chief advantage of the bioassay is that it characterizes the total toxicity of Aconitum herbs. An incorrect toxicity evaluation caused by quantitative analysis of the three alkaloids might be effectively avoided by performing this bioassay. This study revealed that the bioassay is a powerful method for the safety assessment of Aconitum herbs.

Rhein protects against acetaminophen-induced hepatic and renal toxicity.

This study investigated the possible protective effects and mechanism of rhein on Acetaminophen (APAP)-induced hepatotoxicity and nephrotoxicity in rats. Treatment of rats with APAP resulted in severe liver and kidney injuries, as demonstrated by drastic elevation of serum glutamate-pyruvate transaminase (GPT), glutamate-oxaloacetic transaminase (GOT), total bilirubin (TBIL), creatinine (CREA), urea nitrogen (UREA) levels and typical histopathological changes including necrosis, phlogocyte infiltration and fatty degeneration in liver, tubules epithelium swelling and severe vacuolar degeneration in kidney. APAP caused oxidative stress, as evidenced by increased reactive oxygen species (ROS) production, nitric oxide (NO) and malondiadehyde (MDA) levels, together with depleted glutathione (GSH) concentration in the liver and kidney of rats. However, rhein can attenuate APAP-induced hepatotoxicity and nephrotoxicity in a dose-dependent manner. Our results showed that GPT, GOT, UREA and CREA levels and ROS production were reduced dramatically, NO, MDA, GSH contents were restored remarkedly by rhein administration, as compared to the APAP alone treated rats. Moreover, the histopathological damage of liver and kidney were also significantly ameliorated by rhein treatment. These findings suggested that the protective effects of rhein against APAP-induced liver and kidney injuries might result from the amelioration of APAP-induced oxidative stress.

Differences in effects of Zuojin Pills and its similar formulas on Wei cold model in rats.

OBJECTIVE: To explore the effects of Zuojin Pills and its similar formulas on the stomach cold syndrome in a Wei cold model in rats. METHODS: The rat Wei cold model was established by intragastric administration of glacial NaOH, and the gastric mucosa injury indices, together with the levels of motilin and gastrin in the stomach, were determined. The preventive and curative effects of Zuojin Pills and its similar formulas on gastric mucosa injury were investigated. RESULTS: Zuojin Pills and its similar formulas could protect the gastric mucosa in the gastric cold model in rats at different levels. Fanzuojin Pills had the best effect in inhibiting gastric mucosa injury. CONCLUSION: The different pharmacological effects of Zuojin Pills and its similar formulas in the rat gastric cold model were partially correlated with the degrees in cold and heat properties of the formulas.

Investigations of free anthraquinones from rhubarb against alpha-naphthylisothiocyanate-induced cholestatic liver injury in rats.

The protective effects of anthraquinones from Rhubarb, a Chinese herbal medicine, consisting of the root and rhizome of Rheum palmatum L., R. tanguticum Maxim. Ex Balf., or R. officinale Baill. (family Polygonaceae) were investigated and compared in rats with liver injury induced by alpha-naphthylisothiocyanate. alpha-Naphthylisothiocyanate was given intragastrically in rats, liver injury with cholestasis developed within 36 hrs, as indicated by characteristic serum levels of glutamate-pyruvate transaminase, glutamic oxaloacetic transaminase, total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase and total bile acid. The intragastrical administration of rhein, aloe-emodin and physione to alpha-naphthylisothiocyanate-treated rats reduced significantly the serum level of both glutamate-pyruvate transaminase, glutamic oxaloacetic transaminase and the serum total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase and total bile acid. For all hepatic biochemical markers and cholestasis index, rhein was most efficient. By comparison, the administration of emodin and chrysophanol did not reduce the serum levels of hepatic enzymes glutamate-pyruvate transaminase and glutamic oxaloacetic transaminase but decreased the levels of serum total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase, and total bile acid, showing their partial protective effects on cholestatic liver injury. The liver in alpha-naphthylisothiocyanate-treated rats showed cholangiolitic hepatitis characterized by intrahepatic cholestasis, necrosis of hepatocytes and biliary epithelial cells and bile obstruction. The concurrent intragastrical administration of rhein reduced the severity of all morphological alteration, especially the neutrophil infiltration and sinusoid congestion. Rhein, aloe-emodin, and physione all exhibited protective effects on hepatocytes and cholangiocytes against alpha-naphthylisothiocyanate-induced damage, whereas emodin and chrystophanol provided partial protection.

[Study on quality evaluation of Radix Isatis based on analysis of biothermic activity].

OBJECTIVE: To establish a novel pattern and method to evaluate the quality of Radix Isatis based on analysis of biothermic activity. METHODS: Chemical and biothermodynamic methods were used and compared to investigate the quality of different Radix Isatis samples. And a mathematic model was established by computer aided pattern recognition to evaluate the quality of Radix Isatis. RESULTS: The quality of Radix Isatis was partially related to the content of organic acids and polycose, but it could not be correctly recognized by both chemical determination and HPLC fingerprint. On the other hand, the mathematic model based on the main four parameters of biothermodynamic analysis was very correct (misjudgment ratio of 1.39%) to recognize the quality of Radix Isatis. CONCLUSION: The established model in this paper based on analysis of biothermic activity is more accurate and reliable than that of chemical methods to evaluate the quality of Radix Isatis.

Effect of Radix isatidis polysaccharides on immunological function and expression of immune related cytokines in mice.

OBJECTIVE: To investigate the effect of Radix Isatidis polysaccharides (RIP) on the immunological function and expression of immune related cytokines in mice. METHODS: Sixty mice were randomly divided into six groups, the normal group, cyclophosphamide (Cy) model group, Levamisole (positive control) group, RIP low, medium and high dose groups (0.08 g/kg, 0.16 g/kg, 0.32 g/kg, respectively), ten in each group. By detecting the value of abdominal macrophage phagocytic index, serum hemolysin (HC50), proliferation of lymphocytes and expression of related cytokines, interleukin (IL-2) and interferon gamma (INF-gamma), the effect of RIP on immunological function and its mechanism were studied. RESULTS: RIP could improve the level of hemolysin in immunological function depressed mice. The results showed that the value of macrophage phagocytic index in the high dose RIP group increased from 1.11+/-0.13 to 1.42+/-0.26. The level of IL-2 and INF-gamma could be decreased by Cy to 38.12+/-6.88 ng/L and 139.23+/-29.87 ng/L, respectively, while RIP in high dose could increase the secretion of IL-2 and INF-gamma to 53.54+/-14.43 ng/L and 189.91+/-32.63 ng/L, respectively. CONCLUSION: RIP could enhance non-specific immunological function, humoral immunity and cellular immunity in mice.

Investigation on the spectrum-effect relationships of EtOAc extract from Radix Isatidis based on HPLC fingerprints and microcalorimetry.

This work investigated the spectrum-effect relationships between HPLC fingerprints and the anti-bacterial activities of EtOAc extracts from Radix Isatidis. Fingerprints of EtOAc extracts of Radix Isatidis from various sources were established by a High-Performance Liquid Chromatography. The process of Escherichia coli (E. coli) growth affected by EtOAc extracts was monitored using a Thermal Activity Monitor (TAM) Air Isothermal Calorimeter by microcalorimetry. By analyzing the power-time curves, quantitative parameters, such as growth rate constant k, maximum heat-production rate P(m), appearance time t and total heat-production Q were obtained to characterize the interactions of E. coli and the EtOAc extracts from Radix Isatidis. The HPLC fingerprints were investigated using hierarchical clustering analysis. The main thermo-kinetic parameters from the power-time curves were analyzed using principal component analysis. The spectrum-effect relationships between the HPLC fingerprints and anti-bacterial activities were analyzed with multivariant correlation analysis. Close correlation existed between the spectrum-effect relationships of the EtOAc extracts. Salicylic acid in the HPLC fingerprints might be one of the anti-bacterial components. This work provides a general model of the combination of HPLC and microcalorimetry to study the spectrum-effect relationships of EtOAc extracts from Radix Isatidis, which can be used to search for principal components of Radix Isatidis on bioactivity.

An experiment on standardized cell culture assay in assessing the activities of Composite Artemisia Capillaris Tablets against hepatitis B virus replication in vitro.

OBJECTIVE: To explore the activities of Composite Artemisia Capillaris Tablet (CACT) against hepatitis B virus replication in vitro. METHODS: By means of radioimmunoassay (RIA), Dot blot and Southern blot, the surface and e antigen production of 2.2.15 cells, HBV DNA in 2.2.15 cell culture medium and that in 2.2.15 cells were examined respectively. RESULTS: HBsAg, HBeAg values of 2.2.15 cells treated by CACT were lower than those of the control, the HBV DNA quantities in culture medium and in 2.2.15 cells decreased as compared with those cells with no treatment by CACT given to them. CONCLUSION: CACT could inhibit HBV DNA replication, showing its potential antiviral activity in hepatitis B treatment.

[Proceedings of new drug delivery systems and their applications in the traditional Chinese drugs].

By referred to a lot of data, some new drug delivery systems(DDSs) including the Sustained and Controlled DDS, the Targeted DDS, the Transdermal DDS, the Bioadhensive DDS, the PowderJect DDS and the Self-Emulsifying DDS and their applications in TCD since 2000, will be summarized and some latest DDSs in the world including drug-eluting stents, gene therapy carrier system, biological chip, biomolecular motor-powered nanodevice and nanotrap will be also introduced in this paper. The objective of this paper is to introduce the new DDSs proceedings of and their applications in the Traditional Chinese Drugs(TCDs) and to provide some references for the pharmaceutics of TCD. For several recent years, the great success have been achieved in studying the new DDS application in the change of preparation of TCD by the investigators at home, but there is a large difference between at home and at board. So it is necessary to make a greater advance. During the modernization of TCD, there is an effective way that the new drug delivery systems(DDSs) will be applied in the change of the preparation of TCD.

Pharmacological characteristics of novel putative purinoceptors in vascular endothelium.

Using an isolated rat aorta with intact endothelium, a functional bioassay system was created as follows: pre-contract the isolated rat aorta with intact endothelium in the presence of 0.62 micromol/l of norepinephrine, and then add acetylcholine to obtain maximal endothelium-dependent relaxation. In the addition of low concentration of adenosine, a P(1) agonist or ATP, a P(2) agonist to this system, the rat aorta smooth muscle contraction was observed. This observation could not be explained in terms of the classic P(1) and P(2) receptor properties, suggesting that there may be a novel subtype of purinoceptors in the endothelium of the rat aorta. The P(1) and P(2) agonists-induced rat aorta smooth muscle contraction could be blocked by the pretreatments of the bioassay system with a G protein (Gi/o) inhibitor, PTX, and EDNO synthesis inhibitor, L-NAME and cyclooxygenase inhibitor, indomethacine. The data strongly support that this novel purinoceptor may couple with PTX-sensitive G protein, Gi or Go, and the novel purinoceptor-mediated rat aorta smooth muscle contraction is dependent on the endogenous nitric oxide and prostaglandin synthesis. In an additional observation, pathophysiological conditions, such as hypertension, altered the characteristics of the novel receptor. Hypertension caused the novel receptor insensitive to adensone and uncoupling to PTX-sensitive G-proteins and lost of ability to initiate the receptor-mediated prostaglandin synthesis. All together, the novel putative endothelial purinoceptor may play an important role in the control of vascular tone in physiological or pathophysiological statues.

Pharmacological characteristics of the endothelial target for acetylcholine induced vascular relaxation.

The pharmacological characteristics of the endothelial target for acetylcholine induced vascular relaxation were investigated in this experiment. The isolated preparations of arteries were suspended for the measurement of isometric force in modified Krebs-Ringer bicarbonate solution (37 degrees C aerated with 95% O2 and 5% CO2). Similar to acetylcholine, carbachol rather than thiocholine, butylcholine and choline could induce endothelium-dependent relaxation. Among cholinergic receptor agonists, arecoline and oxotremorine rather than nicotine could mimic the effects of acetylcholine. But muscarinic agonist pilocarpine had no effect. This phenomenon was observed in rat, cat and rabbit aorta, as well as cat mesenteric. femoral and renal arteries. The new compound tricyclopinate and phenyl cyclopentyl hydroxyl-ethoxy quinuclidines, the competitive antagonists against muscarinic receptors, displayed noncompetitive antagonism against the endothelial target for acetylcholine. Among the six isomers of the novel compound 2-(2'-cyclopentyl-2'-phenyl-2'-hydroxyl-ethoxy) tropane, the isomers with IS-2alpha-2'R and 1S-2alpha-2'S configuration caused the dose-response curves of acetylcholine for inducing vascular relaxation shift rightward with a parallel manner, while the isomers IR-2alpha-2'R and IR-2alpha-2'S with a nonparallel manner. In addition, the antagonistic effects of the isomer IS-2alpha-2'R against the endothelial target for acetylcholine and against muscarinic receptors were 4570 and 10 times greater than those of the isomer IS-2alpha-2'S respectively. In conclusion, the endothelial target for acetylcholine had the unique pharmacological characteristics different from those of muscarinic receptors.

[Antagonizing effects of novel multipeptid analogues on endothelin receptors and their pharmacological characteristics in cardiovascular system].

AIM: To investigate the antagonistic effects of the novel compounds on vasoconstriction induced by ET-1 and the effect on the blood pressure of stroke-prone spontaneously hypertensive rats. METHODS: Organ bath experiment and whole cardiac function experiment were used. RESULTS: The analogues of o-CPhe-D-Trp-D-Phe(-X)-OH showed good ability against endothelin biological effects. When X was displaced by 3-F, 3-Cl or 4-Cl, the novel compounds inhibit the vascular constriction induced by ET-1 in a concentration-dependent manner, the IC50 +/- L95 were (0.09 +/- 0.05), (0.15 +/- 0.06) or (0.11 +/- 0.03) mumol.L-1 respectively. The blood pressure of stroke-prone spontaneously hypertensive rats was decreased. No significant effect on cardiac function of rats was discovered. CONCLUSION: The results demonstrate that among the six kinds of compounds, those with o-CPhe-D-Trp-D-Phe (-X)-OH configuration showed good biological effects.