Objective: To study the accumulation of mercury in liver, kidney and brain of rats and its toxicity on liver and kidney after 4 weeks of administration of different doses of Zhuhong ointment, in order to provide data reference for the safe clinical use of Zhuhong ointment. Method: Forty-four Sprague-Dawley (SD) rats were randomly divided into 4 groups:control group, normal-dose group (1.875 mg·kg^-1), medium-dose group (37.5 mg·kg^-1), and high-dose group (75 mg·kg^-1). After transdermal administration for consecutive 4 weeks, the mercury content in the urine, blood, liver, kidney and brain of the rats was measured. In addition, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum urea nitrogen (BUN), and serum creatinine (SCr), urine β₂-miSCroglobulin (β₂-BMG) and urine N-acetyl-beta-D glucosidase (NAG) contents were measured, and pathological morphology changes of liver and kidney were observed. Result:Compared with the control group, the levels of blood mercury and urine mercury in Zhuhong ointment groups showed significant increases after administration for 4 weeks(P<0.05,P<0.01). The level of serum ALT was significantly elevated in the high-dose group, and serum SCr was significantly elevated in middle and high-dose groups (P<0.05,P<0.01). Biochemical index in the normal dose remained unchanged. Medium and high doses of Zhuhong ointment destroyed the structure of the hepatic lobule and the radial arrangement of the liver monolayer, shrank the lumen and glomerular, and even led to glomerular balloon enlargement(P<0.05,P<0.01). Normal dose of Zhuhong ointment had no significant effect on liver tissue morphology, but slightly changed kidney tissue morphology. Conclusion:Zhuhong ointment is not toxic at the normal dose, but long-term use can lead to the accumulation of mercury in liver, kidney and bra, which causes liver and kidney toxicity. This study did not find a more sensitive indicator of liver and kidney toxicity than liver and kidney pathology. However, because the rising levels of urinary mercury and blood mercury may predict toxicity, the relationship between mercury exposure and toxicity could be further studied. This study provides a reference for the rational use and toxicity monitoring of Zhuhong ointment.

Objective?To compare the clinical effects of domestic video intubationscope (VIS) versus fiberoptic bronchoscope (FOB) for difficult nasotracheal intubation.?Methods?60 ASA Ⅰ or Ⅱ elective patients with difficult airway, Mallampati class Ⅲ or Ⅳ, aged 22 ～ 68 years, weight 53 ～ 82 kg, were randomly divided into domestic video intubationscope group (group V) and fiber bronchoscope group (group F), 30 cases in each group. The nasotracheal intubation was respectively guided by VIS in group V and FOB in group F. Tracheal intubation time, success rate of tracheal intubation and complications of tracheal intubation were recorded. MAP, HR and SpO2 were recorded at before anesthesia induction (T0), after anesthesia induction (T1), at glottic exposure (T2), at intubation (T3).?Results?Compared with T0, MAP and HR were significantly decreased in both groups at T1(P < 0.05). MAP and HR were significantly increased in both groups at T3 than those at T1(P < 0.05), and there were no significant differences between the two groups (P > 0.05). SpO2 during tracheal intubation was no significantly reduced in both groups. The tracheal intubation time were respectively (76.0 ± 18.0) s and (80.0 ± 20.0) s in group V and group F, and the one-time success rate of intubation in group V and group F were respectively 96.7% and 93.3%, but there were no significant differences between the two groups (P > 0.05). There was no significant difference in the incidence of tracheal intubation complications between the two groups (P > 0.05).?Conclusions?Compared with FOB, difficult nasotracheal intubation guided by domestic VIS also is a safe and reliable, fast and effective method with high intubation success rate and less complications of tracheal intubation.

OBJECTIVE Using bioinformatics methods, to establish Xiao-Xu-Ming decoction (XX-MD)"compound-vasoconstriction G Protein-Coupled Receptors(GPCR)targets"network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD. METHODS Ac-cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da-ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1AR,5-HT1BR),AT1R,β2-AR,hUTR and ETB were retrieved from Bank Pro-tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col-lected and analyzed. The collected data were further used to construct and analyze the network. RE-SULTS 859 single compound structures information in XXMD were generalized following the screen-ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors. Most of the chemical composition effects were associated with different vasoconstric-tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi-ple targets,but also from the interaction between some effective component and multiple targets.

In this study, bioinformatics methods such as molecular docking and network pharmacology were adopted to establish Xiaoxuming Decoction (XXMD) "compound-vasodilatory and vasoconstrictory related G protein-coupled receptors (GPCR) targets" network, then the vascular function regulatory effective components and the potential targets of XXMD were analyzed. Based on the XXMD herb sources, the chemical structures of the compounds were retrieved from the national scientific data sharing platform for population and health pharmaceutical information center, TCMSP database and the latest research literatures. The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties. Then, five kinds of vasodilatory and vasoconstrictory related GPCR crystal structure including 5-HT receptors (5-HT1AR, 5-HT1BR), AT1R, β2-AR, hUTR and ETB were retrieved from RCSB Protein Data Bank database or constructed by homology modeling of Discovery Studio 4.1 built-in modeling tools. After virtual screening by Libdock molecular docking, the highest rated 50 compounds of each target were collected and analyzed. The collected data were further used to construct and analyze the network by Cytoscape 3.4.0. The results showed that most of the chemical composition effects were associated with different vasodilatory and vasoconstrictory related GPCR targets, while a few effective components could be applied to multiple GPCR targets at the same time, therefore forming synergies and vasorelaxant effects of XXMD.
Databases, Protein ; Drugs, Chinese Herbal ; Models, Chemical ; Molecular Docking Simulation ; Receptors, G-Protein-Coupled ; metabolism ; Vasodilation

Objective To construct the pEGFP-C1-CXCL1 eukaryotic expression vector and to investigate the effect of CXCL1 on the proliferation of HepG2 cells under endoplasmic reticulum stress ( ERS).Methods Fragments of CXCL1 were obtained from the cDNA library of HepG2 cells before CXCL1 was cloned into a pEGFP-C1 vector for a recombinant plasmid pEGFP-C1-CXCL1 which was screened and identified by PCR and sequence alignment .Then,the recombinant plas-mid of pEGFP-C1-CXCL1 was transfected into human 293 T cell line and the expression of CXCL 1 was detected by fluores-cence microscopy and Western blotting.pEGFP-C1-CXCL1was furhter transfected into HepG2 cells, and CCK8 was used to detect the inhibitory effect of CXCL1 on tumor proliferation induced by TM in hepatocellular carcinoma .Results pEGFP-C1-CXCL1 was vertified by sequencing analysis .Fluorescence microscopy showed that pEGFP-C1-CXCL1 was transfected into 293T.CXCL1 expression was detected by Western blotting .CCK8 showed that TM inhibited tumor proliferation , while overexpression of CXCL1 decreased the inhabitory rate on cell proliferation of HepG 2 cells under ER stress compared to pEGFP-C1 group and the control group .Conclusion A recombinant pEGFP-C1-CXCL1 plasmid is successfully constructed that can be expressed stably in human 293T cells.Overexpression of CXCL1 can effectively reduce the inhabitory rate of HCC cells induced by the ER stress.

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.

Objective To assess the limit of detection(LOD),sensitivity and specificity of collodial gold immunochrom-atography(GICA)products purchased from two manufacturers under special environmental conditions.Methods The sensitivity and specificity of GICA made in InTec Products, INC.and Beijing WANTAI Biological Pharmacy Enterprise Co., LTD.for detecting HBsAg, anti-HCV and anti-Treponema pallidum(TP)serum samples were evaluated under different conditions(conventional facilities,simulated hot and humid environments and simulated low pressure and hypoxia environments)according to the protocol of kits.LOD was estimated by detecting the standard materials obtained from the National Center for Clinical Laboratory(NCCL)of China.Results LOD for syphilis improved from 2 NCU to 1 NCU using GICA from InTec Products in hot and humid environments.The extreme conditions did not influence the specificity of GICA from the two manufacturers in the course of detection of clinical samples,but the sensitivity of detection was affected.For InTec Products,the sensitivity of hepatitis B virus and syphilis detection was improved in hot and humid environments,but was reduced in low pressure and hypoxia environments.In addition,the sensitivity of hepatitis C virus detection by InTec Products decreased in hot and humid environments.As for WANTAI products,the sensitivity of hepatitis B virus detection was reduced under extreme conditions and that of hepatitis C virus was only influenced by hot and humid environments. Interestingly, extreme conditions had no impact on the sensitivity of syphilis.Conclusion LOD of InTec Products is better than that of the WANTAI products for detection of standard materials from blood-borne diseases.In the process of detecting clinical samples,the sensitivity of the two manufacturers′GICA is influenced by extreme conditions, with the specificity unchanged.Overall, WANTAI products are more stable than those of InTec, and are also less influenced by extreme conditions.

Compound Yizhihao, consists of Radix isatidis, Folium isatidis, Artemisia rupestris, has a significant therapeutic effect on the treatment of influenza and fever. However, the mechanism of its action is still unclear. In this investigation, we collected the key target molecule of influenza disease and the chemical constituents of Compound Yizhihao, and developed Naïve Bayesian classification models based on the input molecular fingerprints and molecule descriptors. The built models were further applied to construct classifiers for predicting the effective constituents. We used the professional network-building software to build the constituent-target network and target-pathway network, which revealed the network pharmacology of the effective constituents in Compound Yizhihao. It will contribute to the further research of mechanism of Compound Yizhihao.

According to different toxicities of various aqueous extracts of Polygonum multiflorum on hepatocyte, the impacts of chemical composition on the safety of P. multiforum was studied. In this study, 8 main chemical compositions in aqueous extracts of P. multiflorum were determined by the established HPLC method; at the same time, the inhibition ratios of different aqueous extracts of P. multiflorum on L02 cell were determined. Afterwards, the potential compounds related to the toxicity of P. multiforum were tentatively found through a multiple correlation analysis. The results showed that P. multiforum with different chemical compositions exhibited great differences in dissolution. The hepatocyte toxicity of P. multiflorum powder was much greater than P. multiflorum lumps. In addition, three constituents closely related to toxicity of P. multiflorum were found by multiple correlation analysis. The study revealed that chemical composition of P. multiflorum is closely related to the hepatotoxicity, and the hepatotoxicity of P. multiflorum powder is greater than that of other dosage forms. This study indicates that P. multiflorum with different chemical compositions show varying toxicity, which therefore shall be given high attention.

OBJECTIVETo observe the effect of Shenluotong Decoction (SD) on serum levels of aldosterone, monocyte chemoattractant protein-1 (MCP-1), α-smooth muscle protein (α-SMA), and nuclear factor-KB (NF-κB) in obstructive nephropathy rats, and to explore the initial mechanism of SD for inhibiting renal interstitial fibrosis.

METHODSTotally 48 healthy Wistar rats were randomly divided into the sham-operation group (n =12) and the model group (n =36). Renal interstitial fibrosis rat model was established by unilateral ureteral obstruction (UUO). After successful modeling, 36 rats were randomly divided into the model group, the Chinese medicine group, and the Western medicine group, 12 in each group. Eplerenone was added in the forage at the daily dose of 100 mg/kg for rats in the Western medicine group. Chinese medicine was added in the forage at the daily dose of 26 g/kg for rats in the Chinese medicine group. Equal volume of normal saline was administered to rats in the sham-operation group and the model group. All medication was performed once daily. The obstructive kidneys were extracted ten days after medication. The pathomorphological changes were observed. The contents of serum aldosterone and MCP-1, and the protein or mRNA expression of MCP-1, α-SMA, and NF-KB were detected.

RESULTSCompared with the sham-operation group, infiltration of a large amount of inflammatory cells and collagen deposition significantly increased, serum contents of aldosterone and MCP-1 obviously increased (P < 0.01), the expression of MCP-1 mRNA and protein were significantly up-regulated (P <0.01), the protein expression of α-SMA and NF-KB were significantly enhanced in the model group (P <0.01). Com- pared with the model group, infiltration of inflammatory cells and renal collagen deposition were attenua- ted in the Chinese medicine group and the Western medicine group, the serum MCP-1 level were reduced, and the mRNA and protein expression of MCP-1 were significantly down-regulated (P <0.01), the protein expression of α-SMA and NF-KB were obviously inhibited (P <0. 01). At the same time, serum aldosterone level was reduced in the Chinese medicine group (P <0.01).

CONCLUSIONSinflammatory lesions of the renal tissue could promote the progress of interstitial fibrosis in rats with obstructive nephropathy. SD could attenuate interstitial fibrosis through reducing serum contents of aldosterone and MCP-1, down-regulating MCP-1/ NF-KB, and inhibiting the expression of α-SMA.

Animals ; Chemokine CCL2 ; drug effects ; metabolism ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Fibrosis ; Kidney ; drug effects ; Kidney Diseases ; drug therapy ; genetics ; NF-kappa B ; drug effects ; metabolism ; RNA, Messenger ; biosynthesis ; Rats, Sprague-Dawley ; Ureteral Obstruction ; drug therapy ; genetics