OBJECTIVE:To evaluate the antineoplastic effects of non-alkaloid components from Gelsemium elegans Benth in vitro and in vivo and to study the correlation between antineoplastic effects and toxicity.METHODS:The cell proliferation inhibition effect of every component on tumor cells in vitro was studied by MTT method,the antineoplastic activity of non-alkaloid components were comprehensively evaluated through acute toxicity testing on mice,the inhibition effect test on H 22 of liver tumor-bearing mice and the test on the effect on immunizing index.RESULTS:The antineoplastic activity of non-alkaloid in Gelsemium elegans in vitro surpassed alkaloid,and in which the component 2 could significantly inhibit H 22 tumor growth in mice,the thymus gland indexes were significantly higher in treatment group than non-treatment tumor-bearing mice.However,the other components showed no significant effect on tumor growth and those with stronger toxicity showed no antineoplastic activity.CONCLUSIONS:The non-alkaloid components from Gelsemium elegans Benth show anti-neoplastic effects and enhancement property on immune function,however,its antineoplastic effects in vitro and in vivo have no obvious correlation with toxicity.

Object To define the optimal proportion of four ingredients in Danxintong (DXT). Methods Uniform design method combined with pharmacodynamics (Rat acute myocardial ischemia model was used in this study) was used. Results The optimal proportion and components of DXT (Composed of Rhizoma Chuanxiong, Rhizoma Cyperi, Borneolum Syntheticum, and paeonol) were 5∶ 1.7∶ 1.4∶ 4.4; DXT 138 mg/kg could obviously inhibit acute myocardial ischemia of rats induced by iso prenaline (Iso) and pituiturin (Pit). DXT has antimyocardial ischemia effects in preliminary experimental studies. Conclusion Uniform design method is an effective method to define the optimal proportion of ingredients in DXT;

OBJECTIVE To determine the category of gene cassettes in type 1 integrons of multi-resistant Acinetobacter baumannii from Shenyang.METHODS Fifty clinical isolates were collected from the First Affiliated Hospital of China Medical University and K-B test was used to determine the susceptibility and the results were read based on Clinical and Laboratory Standards Institute(CLSI) of the USA.PCR was used to detect the existance of integron,and DNA sequencing was also required.RESULTS There are thirty-two isolates positive for integron.Sequencing analysis showed the integrons carried two different known genes(arr-3 and aacA4).CONCLUSIONS The results show the potential risk of integron dissemination among different strains of A.baumannii.

Object To study the phsiochemical properties of storax ? cyclodextrin (? CD) inclusion complex Methods The inclusion complex was identified by the methods of TLC, X ray powder diffractometry and IR The solubility and dissolution rate of cinnamic acid in inclusion complex were investigated by HPLC Results The TLC showed that the main composition of storax had no change before and after being included by ? CD The spectra of X ray powder diffractometry and IR of the inclusion complex were remarkably different from those of storax and storax ? CD mixture It was shown a great improvement of the solubility and dissolution rate of cinnamic acid in the inclusion complex in 0 1 mol/L HCl, pH 6 6 and pH 7 5 phosphate buffer solution Conclusion The storax ? CD inclusion complex exhibits some new physical characteristics and its physiochemical properties are greatly changed comparing with those of storax

Objective To investigate changes in coagulation function and inflammation levels during sepsis.Methods A rat model of sepsis was established using the multiple infection sepsis model(MIM)based on cecal ligation and puncture.Forty-eight male Sprague-Dawley rats were assigned randomly to the following groups:control group,sham group,4 h sepsis group,8 h sepsis group,12 h sepsis group,and 16 h sepsis group(n=8 per group).Inflammatory markers and coagulation-related indicators were measured by enzyme-linked immunosorbent assay and coagulation analysis.Results(1)Lipopolysaccharide(LPS)and interleukin-6(IL-6)levels were significantly higher in the model rats at all time points compared with the sham group(P＜0.001).LPS and IL-6 levels increased gradually with disease progression,with no further changes in LPS after 12 hours.(2)Prothrombin time(PT)was significantly prolonged in the middle and late stages of the sepsis model,starting from 8,compared with the sham group(P＜0.01).(3)Partially activated prothrombin time(APTT)time was significantly prolonged in the 8,12,and 16 h groups compared with the sham group(P＜0.05,P＜0.01).APTT gradually lengthened from 8 h,but approached control levels thereafter.(4)Fibrinogen(Fbg)content was significantly higher in all sepsis groups,except for the 8 h group,compared with the sham group(P＜0.01).(5)Fibrin degradation products(FDP)differed significantly between the control and sham groups(P＜0.01),but not between the sham and sepsis groups.(6)Antithrombin-Ⅲ(AT-Ⅲ)levels decreased significantly throughout each stage of sepsis progression compared with the sham group(P＜0.01),and AT-Ⅲ showed a downward trend with the course of disease,with significant differences among the 4,8,and 16 h groups.Conclusions The MIM rat model can reflect the development of inflammatory and blood coagulation disorders and their relationship during the course of sepsis,and may thus provide a good foundation for further research into the disease course of sepsis.

Objective To evaluate the predictive values of interleukin (IL)-2 and soluble interleukin 2 receptor (sIL-2R) in the serum and cerebrospinal fluid in early intracranial infection,and provide the reference for choosing diagnostic markers of early intracranial infection after craniotomy.Methods From January 2014 to January 2016,36 patients with intracranial infection after craniotomy in our hospital were chosen as infection group,and 45 patients without intracranial infection were as non-infection group.The body temperature and levels ofcerebrospinaI fluid glucose,blood white blood cell (WBC),cerebrospinal fluid WBC,serum IL-2,cerebrospinal fluid IL-2,serum sIL-2R and cerebrospinal fluid sIL-2R were compared between the two groups.The diagnosis values of IL-2 and sIL-2R in serum and cerebrospinal fluid in intracranial infection were analyzed by receiver operating characteristic curve (ROC) curve.The sensitivity and specificity of IL-2 and sIL-2R in the serum and cerebrospinal fluid in intracranial infection were compared between the two groups.Results The body temperature of the two groups showed no statistical difference (P＞0.05).As compared with those in the non-infection group,the glucose of cerebrospinal fluid in the infection group significantly decreased (P＜0.05),the blood WBC,cerebrospinal fluid WBC,serum IL-2,cerebrospinal fluid IL-2,serum sIL-2R and cerebrospinal fluid sIL-2R in the infection group significantly increased (P＜0.05).The areas under of curve for body temperature,glucose of cerebrospinal fluid,blood WBC,cerebrospinal fluid WBC,serum IL-2,cerebrospinal fluid IL-2,serum sIL-2R and cerebrospinal fluid sIL-2R,respectively,were 0.671,0.718,0.698,0.741,0.714,0.927,0.722 and 0.968;the sensitivity of those indexes,respectively,was 61.1％,63.9％,69.4％,91.7％,88.9％,91.7％,86.1％and94.4％;the specificityofthoseindexes,respectively,was 48.9％,82.2％,60.0％,55.6％,62.2％,88.9％,66.7％ and 91.1％.Conclusion The IL-2 and sIL-2R levels in serum and cerebrospinal fluid have decided values in diagnosis of intracranial infection after craniotomy,but the sensitivity and specificity of IL-2 and sIL-2R in cerebrospinal fluid are higher than others.

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Ferroptosis is a new programmed cell death dependent on iron ions.Ferroptosis can be induced by endogenous or exogenous pathways, and cells exhibit specific cell morphological signs and are regulated by a variety of molecular mechanisms.In recent years, more and more studies have shown that ferroptosis plays an important role in the treatment of cancer.This article summarizes the mechanism of ferroptosis in bladder cancer and the regulation of cancer cells, as well as the role of ferroptosis-related factors, non-coding RNA regulation, N6-methyladenosine (m6A), amino acid metabolism and autophagy dependent ferroptosis in the growth and proliferation of bladder cancer, with a view to provide new strategies for the treatment of bladder cancer.

ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）. MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg^-1·d^-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg^-1·d^-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg^-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively. ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）. ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg^-1·d^-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg^-1·d^-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.