Objective:To explore the therapeutic effect of compound Kuijie Ankang Decoction on ulcerative colitis (UC) model mice by non targeted metabonomics; To explore its mechanism.Compound Kuijie Ankang.Methods:The mice were randomly divided into blank control group, model group, Kuijie Ankang Decoction group and sulfasalazine group, with 12 mice in each group. Except the blank control group, the other groups were given 1.5% DSS solution for free drinking to prepare UC model. After successful modeling, Kuijie Ankang Decoction group was intragastrically administered with compound Kuijie Ankang Decoction of 9.68 g/kg, sulfasalazine group was intragastrically administered with sulfasalazine capsule suspension of 320 mg/kg, model group and blank control group were intragastrically administered with equal volume of purified water, once a day, for 7 consecutive days. The body mass and disease activity index (DAI) score of mice were measured. ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the colon tissue of mice; the protein expressions of Claudin-1 and Zo-1 in colon tissue were detected by immunofluorescence method. HE staining was used to observe the pathological changes in the colon, and UHPLC-OE-MS technology was used to analyze the endogenous metabolite structure of mouse colon tissue, differential metabolites and related metabolic pathways were screened.Results:Compared with the model group, the colon length in Kuijie Ankang Decoction group and sulfasalazine group increased ( P<0.01), the DAI score decreased ( P<0.01), the levels of TNF-α, IL-1β and IL-6 in colon tissue decreased ( P<0.01), the level of IL-10 increased ( P<0.01), and the average optical density of Claudin-1 and Zo-1 protein increased ( P<0.01 or P<0.05). Metabolomics analysis identified 26 potential differential metabolites, including nicotinamide adenine dinucleotide, guanine, gamma aminobutyric acid, and thiamine, affecting 26 key metabolic pathways, including lysine biosynthesis, thiamine metabolism, cysteine and methionine metabolism. Conclusion:Kuaijie Ankang Decoction may improve metabolites such as Gamma aminobutyric acid and thiamine through metabolic pathways such as lysine biosynthesis to alleviate inflammatory reactions, thereby exerting therapeutic effects on ulcerative colitis in mice.

Gastric cancer is a malignant tumor of the digestive system with strong invasiveness and a high metastasis rate.Its morbidity and mortality rank among the top five in the world and the prognosis is closely related to the disease stage.Multidisciplinary comprehensive treatment based on systemic antitumor drugs is generally adopted in patients with advanced or metastatic gastric can-cer,but the prognosis is typically poor.With the in-depth research on the tumor microenvironment,the development of multi-omics technology,and the application of immunotherapy and neoadjuvant chemoradiotherapy,the therapeutic effect of advanced gastric can-cer has been initially improved,and immunotherapy has become the most potential of the treatment strategies.Many studies have found that Helicobacter pylori(Hp)infection status is closely related to the efficacy of immunotherapy for gastric cancer,especially im-mune checkpoint inhibitors(ICIs),but there is not clear whether it has advantages or disadvantages.This article reviews the current research on the efficacy of Hp on ICIs in advanced gastric cancer to provide ideas for further research on the interaction between Hp in-fection and tumor immunotherapy.

Gastric cancer is a malignant tumor of the digestive system with strong invasiveness and a high metastasis rate.Its morbidity and mortality rank among the top five in the world and the prognosis is closely related to the disease stage.Multidisciplinary comprehensive treatment based on systemic antitumor drugs is generally adopted in patients with advanced or metastatic gastric can-cer,but the prognosis is typically poor.With the in-depth research on the tumor microenvironment,the development of multi-omics technology,and the application of immunotherapy and neoadjuvant chemoradiotherapy,the therapeutic effect of advanced gastric can-cer has been initially improved,and immunotherapy has become the most potential of the treatment strategies.Many studies have found that Helicobacter pylori(Hp)infection status is closely related to the efficacy of immunotherapy for gastric cancer,especially im-mune checkpoint inhibitors(ICIs),but there is not clear whether it has advantages or disadvantages.This article reviews the current research on the efficacy of Hp on ICIs in advanced gastric cancer to provide ideas for further research on the interaction between Hp in-fection and tumor immunotherapy.

Ulcerative colitis(UC)is a common disease of the digestive system.Phosphatidylinositol-3-kinase(PI3K)/synuclein/threonine kinase(AKT)is closely related to cell survival,apoptosis,inflammation and other biological processes,and the expression levels of PI3K and AKT significantly increase during the course of UC,with accelerated apoptosis,improved inflammation,and damaged intestinal mucosal barrier function.In recent years,a large number of basic and clinical trials have been conducted on PI3K/AKT signaling pathway in TCM,and the results indicate that PI3K/AKT signaling pathway is expected to be an important potential target for UC treatment.This article analyzed the mechanism of the regulation of PI3K/AKT signaling pathway in TCM from monomer,extract,compound and acupuncture,and suggested that the regulation of this signaling pathway is of great significance for the prevention and treatment of UC,and provide reference for drug development.

OBJECTIVE To study the improvement effects and its mechanism of catalpol on testicular lesions in KK-Ay spontaneous diabetic mice on the basis of glycolysis process mediated by advanced glycation end products （AGEs） and their receptors （RAGE）. METHODS KK-Ay spontaneous diabetic mice fed with high-fat diet were used as diabetic model， and then randomly divided into model group， catalpol group （100 mg/kg）， aminoguanidine group （AGEs inhibitor， 100 mg/kg） and FPS- ZM1 group （RAGE inhibitor， 1 mg/kg）， and C57BL/6J mice fed in the same period were set as normal group， with 6 mice in each group. The catalpol group and aminoguanidine group mice were given relevant medicine intragastrically， normal group and model group mice were given constant volume of normal saline intragastrically， and FPS-ZM1 group mice were given relevant medicine 1 mL/g intraperitoneally， for consecutive 8 weeks. After the last administration， the body mass， fasting blood glucose， 24-hour food intake， water consumption， urine volume， testicular organ coefficient， and sperm motility of the mice were measured； pathological morphology and ultrastructural structure of testicular tissue were observed； the levels of reduced glutathione （GSH）， superoxide dismutase （SOD）， lactate dehydrogenase （LDH） and sugar metabolites in testicular tissue of mice were detected； pathway enrichment analysis was performed； the level of AGEs in serum and testicular tissue， protein expressions of RAGE， B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）， and mRNA expressions of key rate-limiting enzymes [hexokinase （HK）， phosphofructose kinase （PFK）， pyruvate kinase （PK）， LDH] in testicular tissue were alldetected. RESULT S Catalpol could significantly improve the general symptoms， testicular organ coefficients and motility ofsperm in KK-Ay spontaneous diabetic mice （P＜0.05 or P＜0.01）. The morphology and ultrastructure of spermatogenic cells in each layer of the seminiferous tubules were all improved. The levels of GSH， SOD and LDH in testicular tissue，the levels of the metabolic product glucose fructose-1，6-diphosphate， 3-phosphate glycerate， 3-phosphate glyceraldehyde， lactic acid and pyruvate， the expressions of HK， PFK， PK and LDH mRNA were all significantly increased（P＜0.05 or P＜0.01）； the levels of AGEs in serum and testicular tissue， the expression of RAGE protein and the ratio of Bax to Bcl-2 in testicular tissue were significantly decreased（P＜0.05 or P＜0.01）. Aminoguanidine and FPS-ZM1 could significantly improve the levels of most of above indicators in mice（P＜0.05 or P＜0.01）. CONCLUSIONS Catalpol shows significant improvement effects on testicular lesions of KK-Ay spontaneous diabetic mice， and its mechanism of action was associated with upregulation of AGEs/RAGE signaling pathway- mediated glycolysis.

OBJECTIVE To compare the change law of multi-components in the extraction process between Liuwei dihuang powder decoction pieces and traditional decoction pieces （hereinafter referred to as powder decoction pieces and traditional decoction pieces）， and to provide scientific basis for the modern technology research of Liuwei dihuang formula. METHODS Taking powder decoction pieces and traditional decoction pieces as samples， the samples were taken when soaking for 60 min， at 0， 5， 10， 15， 20， 25， 30， 40， 50， 60 min of the first decocting and at 5， 10， 20， 30， 40 min of the second decocting， respectively. HPLC method was used to establish the fingerprints of 2 kinds of decoction pieces with different decocting time. The similarity evaluation and peak identification were performed. The contents of 8 components including 5-hydroxyfurfural， catechin， monoglycoside， loganin， swertin glycoside， dihydroquercetin， paeonol and benzoyl paeoniflorin were all determined. RESULTS With different decocting time， the similarties between 2 kinds of decoction pieces and their respective control fingerprints R were all greater than 0.98. In the fingerprints of traditional decoction pieces， five chromatographic peaks were identified， namely， 5- hydroxyfurfural， monetin， swertiaoside， dihydroquercetin and paeonol； in the fingerprints of powder decoction pieces， six chromatographic peaks were identified， namely， 5-hydroxyfurfural， monoglycoside， swertiamarin， dihydroquercetin， paeonol and benzoyl paeoniflorin. The results of content determination showed that in the first 5 minutes of the first decocting， the decocting rate of almost all the ingredients in the powder decoction pieces was faster than that of the traditional decoction pieces； after 40 min， the contents of other active ingredients were lower than those of traditional decoction pieces except for 5-hydroxyfurfural and paeonol. In the process of second decocting， except for paeonol and loganin， the contents of other ingredients in powder decoction pieces were higher than that in traditional decoction pieces； catechin was completely decocted from the traditional decoction pieces in the first decocting， while it could still be detected in the powder decoction pieces in the second decocting. There was little difference in the total decocted amount of the 8 ingredients in the two decoction pieces. CONCLUSIONS The chemical composition of powder decoction pieces of Liuwei dihuang formula has no obvious advantages compared with traditional decoction pieces， and can not save the decocting time and the amount of medicinal materials.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

Objective To examine the sex differences in prescribing patterns of psychotropic drugs and drug-induced side effects in schizophrenia patients in China. Methods Using the same design and a standardized protocol as in 2002 and 2006, the cross-sectional survey was conducted from July to August, 2012 in 45 psychiatric hospitals/centers in 10 provinces and municipalities in China. Inpatients and outpatients with schizophrenia were consecutively screened for eligibility for this study. Sociodemographic characteristics and prescription pattern were collected by using a modified questionnaire for the study. Data comparisons between male and female were performed with univariate analysis. Multiple logistic regression analysis was employed to determine the gender differences in prescription pattern and drug-induced side effects. Results The sample consisted of 2 260 male and 1 979 female patients. Univariate analyses showed that male patients were younger than female patients(t=5.398), having an earlier age at onset(t=5.662), higher percentage of being employed(χ2=31.597), and more negative symptoms(χ2=10.814)and aggressive behavior (χ2=5.816), more likely to receive clozapine (23.9%(472/1 979) vs. 28.5%(645/2 260),χ2=11.955), higher antipsychotic doses(476 mg vs. 514 mg,F=14.003), less use of antidepressants (7.9%(156/1 979) vs. 6.0%(136/2 260),χ2=5.722)and benzodiazepines(23.9%(472/1 979)vs. 20.0%(451/2 260),χ2=9.396), more frequent tardive dyskinesia(1.3%(25/1 979)vs. 2.1%(47/2 260),χ2=4.212)and less weight gain(11.0%(218/1 979)vs. 7.7%(173/2 260),χ2=14.233)and prolactin elevation(3.2%(63/1 979)vs. 1.7%(39/2 260),χ2=9.548;all P<0.05). In multivariate analyses, greater rate of clozapine use (OR=1.268,P=0.001), less rate of benzodiazepines use(OR=0.841,P=0.025) and antidepressants(OR=0.78,P=0.045),higher rate of tardive dyskinesia(OR=1.879,P=0.014)and less weight gain (OR=0.669,P=0.001) and prolactin elevation (OR=0.527,P=0.003) were independently associated with the male sex. Conclusion Gender is one of the independent contributors to psychotropic prescription pattern and side effects of antipsychotics in Chinese schizophrenia patients. Gender differences should be given more attention in research and clinical practice.

Objective To examine the sex differences in prescribing patterns of psychotropic drugs and drug-induced side effects in schizophrenia patients in China. Methods Using the same design and a standardized protocol as in 2002 and 2006, the cross-sectional survey was conducted from July to August, 2012 in 45 psychiatric hospitals/centers in 10 provinces and municipalities in China. Inpatients and outpatients with schizophrenia were consecutively screened for eligibility for this study. Sociodemographic characteristics and prescription pattern were collected by using a modified questionnaire for the study. Data comparisons between male and female were performed with univariate analysis. Multiple logistic regression analysis was employed to determine the gender differences in prescription pattern and drug-induced side effects. Results The sample consisted of 2 260 male and 1 979 female patients. Univariate analyses showed that male patients were younger than female patients(t=5.398), having an earlier age at onset(t=5.662), higher percentage of being employed(χ2=31.597), and more negative symptoms(χ2=10.814)and aggressive behavior (χ2=5.816), more likely to receive clozapine (23.9%(472/1 979) vs. 28.5%(645/2 260),χ2=11.955), higher antipsychotic doses(476 mg vs. 514 mg,F=14.003), less use of antidepressants (7.9%(156/1 979) vs. 6.0%(136/2 260),χ2=5.722)and benzodiazepines(23.9%(472/1 979)vs. 20.0%(451/2 260),χ2=9.396), more frequent tardive dyskinesia(1.3%(25/1 979)vs. 2.1%(47/2 260),χ2=4.212)and less weight gain(11.0%(218/1 979)vs. 7.7%(173/2 260),χ2=14.233)and prolactin elevation(3.2%(63/1 979)vs. 1.7%(39/2 260),χ2=9.548;all P<0.05). In multivariate analyses, greater rate of clozapine use (OR=1.268,P=0.001), less rate of benzodiazepines use(OR=0.841,P=0.025) and antidepressants(OR=0.78,P=0.045),higher rate of tardive dyskinesia(OR=1.879,P=0.014)and less weight gain (OR=0.669,P=0.001) and prolactin elevation (OR=0.527,P=0.003) were independently associated with the male sex. Conclusion Gender is one of the independent contributors to psychotropic prescription pattern and side effects of antipsychotics in Chinese schizophrenia patients. Gender differences should be given more attention in research and clinical practice.

Objective To study the application value of the combined detection of serum HE4 ,CAl25 ,CA72‐4 and IL‐6 in the di‐agnosis of ovarian malignant tumor .Methods The serum levels of CA125 and CA72‐4 were determined by ECLI ,and the serum levels of HE4 and IL‐6 were determined by ELISA in 32 patients with ovarian cancer ,56 patients with benign ovarian disease and 40 healthy controls .The detection results were performed the statistical analysis .Results The serum levels of HE4 ,CAl25 ,CA72‐4 and IL‐6 in the ovarian cancer group were significantly higher than those in the other two groups with statistically significant differ‐ences(P< 0 .01) ;the sensitivity of CA125 detection in the single index detections was highest(75 .0% ) ,the specificity of HE4 was highest(83 .9% ) ,the highest diagnostic efficiency of single index detection was 79 .5% .The sensitivity ,specificity and efficiency of the combined detection for diagnosis were 96 .9% ,71 .4% and 80 .7% .Except the specificity ,the sensitivity and diagnostic efficien‐cy of the combined detection were higher than those of any one of single index detection .Conclusion The combined detection of se‐rum HE4 ,CAl25 ,CA72‐4 and IL‐6 could increase the diagnostic efficiency of ovarian cancer and conduces to the diagnosis and help to the diagnosis and differential diagnosis of ovarian malignancies .