OBJECTIVE To study the difference of Huangqin decoction combined with Paeoniae Radix Alba(BS) and Paeoniae Radix Rubra(CS)'s effect on ulcerative colitis(UC) based on network pharmacological analysis and animal experiment. METHODS The active constituents of BS and CS were retrieved from TCMSP database and literature, and the potential target was predicted by Swiss Target Prediction. Ulcerative Colitis was used as key words to search disease targets in DisGenet, OMIM, and Genecard databases. The intersection target was obtained by Venny 2.1.0. Cytoscape 3.7.2 software was used to construct network of drug-consumption targets. The STRING platform was used for protein-protein interaction(PPI) network analysis, and Metascape database was applied for GO/WIKI analysis. A dextran sulfate sodium(DSS) induced UC mouse model was established to compare the anti-UC effects of Huangqing decoction combined with BS(HQT-BS) and CS(HQT-CS), respectively. RESULTS There were 7 active components of HQT-BS and 11 active components of HQT-CS in the treatment of ulcerative colitis, respectively, 5 of which were the same. There were 146 and 157 targets respectively, 106 of which were the same. The core targets of HQT-BS were SRC, HSP90AA1, and PIK3R1, while the core targets of HQT-CS were SRC, HSP90AA1, and STAT3. WIKI enrichment analysis showed that several signaling pathways were shared by both BS and CS, such as EGFR tyrosine kinase inhibitor resistance, Notch signaling pathway. EGF/EGFR signaling pathway was the specific pathway related to BS, while Nuclear receptors meta-pathway and Kit receptor signaling pathway were the specific pathways related to CS, respectively. Animal experiments showed that both HQT-BS and HQT-CS could significantly improve colon shortening and tissue pathological alternation induced by DSS. However, HQT-CS was more effective in reducing the expression of interleukin-6 and neurogenic locus notch homolog protein1. CONCLUSION Both HQT-BS and HQT-CS have anti-UC effect, and HQT-CS is the better one.

Objective:To investigate the clinical significance of serum glial fibrillary acidic protein(GFAP)level in middle-aged and elderly patients with Parkinson's disease(PD).Methods:In the prospective study, a total of 39 patients with PD hospitalized in the Department of Neurology of Zhejiang Hospital affiliated to Zhejiang University School of Medicine, and 17 healthy subjects from January 2017 to May 2021 were collected.Serum GFAP levels in the PD group and healthy control(CT)group were detected by an ultra-sensitive Simoa hypersensitive protein detection technology.The correlations of serum GFAP level with age, gender, clinical presentation type, depression score, Montreal Cognitive Assessment Scale(MOCA)score and Mini-Mental State Examination(MMSE)score were analyzed.Results:The level of serum GFAP was significantly higher in PD group(219.6±166.2)ng/L than in CT group(109.9±56.6)ng/L( P< 0.01). In PD group, there was no correlation of serum GFAP with age, gender, clinical classification, depression and MOCA score(age: r=0.042, gender: r=-0.142, depression score: r=0.076, MoCA score: r=0.014, all P>0.05); but there was a significant negative correlation between serum GFAP and MMSE score( r=-0.433, P< 0.05). Conclusions:There is a negative correlation between serum GFAP level and MMSE score, suggesting that the increase of serum GFAP might be suggestive of cognitive decline in Parkinson's disease patients to some extent, which should be paid attention to in clinical work.

A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates

A large number of investigations and studies abroad have focused on the quality of life of breast cancer long-term survivors (BCLS) and its influencing factors. Although their long-term quality of life has been improved, the improvement of their quality of life is affected by many factors. At present, there are few researches on BCLS in China. This research systematically searches CNKI, Wanfang, PubMed and Web of Science, includes relevant literature on quality of life of BCLS in recent years and describes the current domestic and foreign research status of quality of life of BCLS. It reviews from four aspects, including general demographic factors, disease-related factors, psychosocial factors and exercise, in order to provide reference for the follow-up research and practice.

Objective: To investigate the clinical value of lymph node dissection (LND) in the radical resection of intrahepatic cholangiocarcinoma (ICC). Methods: The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 448 patients with ICC who were admitted to 12 medical centers from December 2011 to December 2017 were collected, including 279 in the Eastern Hepatobiliary Surgery Hospital of Navy Medical University, 32 in the Mengchao Hepatobiliary Hospital of Fujian Medical University, 21 in the First Hospital Affiliated to Army Medical University, 20 in the Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College, 19 in the West China Hospital of Sichuan University, 18 in the Second Hospital Affiliated to Zhejiang University School of Medicine, 18 in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 16 in the Beijing Friendship Hospital Affiliated to Capital Medical University, 10 in the Xuanwu Hospital Affiliated to Capital Medical University, 7 in the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, 5 in the Beijing Tiantan Hospital Affiliated to Capital Medical University, and 3 in the Affiliated Hospital of North Sichuan Medical College. There were 281 males and 167 females, aged from 22 to 80 years, with a median age of 57 years. Of the 448 patients, 143 with routinely intraoperative LND were divided into LND group and 305 without routinely intraoperative LND were divided into control group, respectively. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups after matching; (2) intraoperative and postoperative situations; (3) follow-up; (4) survival analysis. Patients were followed up by outpatient examination, telephone interview and email to detect survival of patients and tumor recurrence up to October 31, 2018 or death. Follow-up was conducted once every 3 months within postoperative 1-2 years, once every 6 months within postoperative 2-5 years, and once a year after 5 years. The propensity score matching was realized using the nearest neighbor method with 1∶1 ratio. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to calculate survival rates and draw survival curve, and Log-rank test was used to perform survival analysis. Univariate analysis and multivaraiate analysis were conducted using the Log-rank test and COX regression model, respectively. Results: (1) The propensity score matching conditions and comparison of general data between the two groups after matching: 286 of 448 patients had successful matching, including 143 in each group. The number of males and females, cases with hepatitis, cases with grade A and B of Child-Pugh classification, cases with distance from margin to tumor <1 cm and ≥1 cm, cases with highly, moderately, and poorly differentiated tumor, cases with anatomical hepatectomy and nonanatomical hepatectomy before propensity score matching were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 204, 101, 121, 165, 140, 207, 98, 251, 54, 124, 181 in the control group, respectively, showing significant differences in the above indices between the two groups (χ²=7.079, 11.885, 7.098, 14.763, 5.184, 8.362, P<0.05). After propensity score matching, the above indices were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 79, 64, 29, 88, 55, 71, 72, 112, 31, 74, 69 in the control group, respectively, showing no significant difference in the above indices between the two groups (χ²=0.056, 0.329, 2.158, 0.014, 0.936, 1.400, P>0.05). (2) Intraoperative and postoperative situations: the operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, cases with postoperative complications, and duration of postoperative hospital stay were 265 minutes (range, 160-371 minutes), 300 mL (range, 200-500 mL), 37, 46, 12 days (range, 9-17 days) for the LND group, and 59 minutes (range, 46-250 minutes), 200 mL (range, 100-400 mL), 24, 25, 9 days (range, 7-11 days) for the control group, respectively. There was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups (Z=1.700, χ²=3.520, P>0.05). There were significant differences in the operation time, cases with postoperative complications, and duration of postoperative hospital stay (Z=6.520, χ²=8.260, Z=4.270, P<0.05). (3) Follow-up: 143 patients in the LND group was followed up for 18-26 months. The 1-, 3-, 5-year survival rates were 66.9%, 32.8%, 25.0%, and the median survival time was 22.0 months (range, 18.0-26.0 months). In the control group, 143 patients were followed up for 11-32 months. The 1-, 3-, 5-year survival rates were 71.7%, 38.0%, 31.0%, and the median survival time was 22.0 months (range, 11.0-32.0 months). There was no significant difference in the overall survival between the two groups (χ²=0.466, P>0.05). (4) Survival analysis: results of univariate analysis showed that distance from margin to tumor, tumor diameter, the number of tumors, microvascular tumor thrombus, and lymph node metastasis by pathological examination were related factors for prognosis of patients undergoing radical resection of ICC (χ²=10.662, 9.477, 16.944, 6.520, 11.633, P<0.05). Results of multivariate analysis showed that distance from margin to tumor<1 cm, tumor diameter>5 cm, multiple tumors, microvascular tumor thrombus, positive lymph node metastasis by pathological examination were independent risk factors for prognosis of patients undergoing radical resection of ICC (hazard ratio=0.600, 1.571, 1.601, 1.750, 1.723, 95% confidence interval: 0.430-0.837, 1.106-2.232, 1.115-2.299, 1.083-2.829, 1.207-2.460, P<0.05). Conclusion Lymph node metastasis is an independent risk factor affecting the prognosis of ICC patients, and it is necessary to perform LND in radical resection for patients with ICC and lymph node metastasis.

Objective To explore the feasibility of the deep convolutional neural network (DCNN) judging the indications and prognosis of the total knee arthroplasty based on the trained DCNN computer learning system.Methods C1FAR-10 DCNN model based on TensorFlow (an open source system,Google,USA) optimized by Alex Krizhevsky were constructed.There were 400 cases with knee osteoarthritis from different databases used for analysis.Three hundred patients underwent total knee arthroplasty,while 100 did not.X-ray of 200 preoperative cases from the 400 cases and their enlarged image (50 times) were applied for training DCNN,while the enlarged images from other 200 cases were used to test the DCNN.The correlation and the regression between judgment of the DCNN and clinical truth were analyzed.The clinical truths were rechecked three times and were confirmed by treatment results.Pearson correlation and linear regression analysis were used.The relation test of the software was only used as a reference.Results There was no significant difference between the baseline of cases for learning and test.After learning 200 cases,the DCNN judged the 10 000 cases enlarged from remaining 200 cases.The correlation between the DCNN judgment and the clinical truth was not significant (r=0.000,F=0.001,P=0.970).False positive was observed in 1 681 cases,false negative in 3 296.After enlarged to 10 000 images,the correlation between the two judgments was significant (F=11 228.735,P=0.000,r=0.727 and R2=0.529).The software detection precision was 0.860.Conclusion DCNN can be applied in judging the indications of the total knee arthroplasty.Large sample size can improve the accuracy of the judgment significantly.

Objective To study the impacts of alcohol dependence on the anticonvulsant effect of diazepam. Meth?ods Kunming mice (n=36) were divided into 3 groups (n=12 in each group), Alcohol Dependence Group(A group), Diaze?pam Group(D group)and Normal Saline Group(N group). A group received an intraperitoneal injection with a 0.2 mL dose of 0.8%alcohol in NS (normal saline) , while both D and N group received an injection with a 0.2 mL dose of NS without alco?hol , twice a day. Mice’s autonomic activities were monitored every day. After 7 days, the electroconvulsive experiment was performed. Both A and D group were given a weight-based dose of 0.05 mL/10 g of 0.05%diazepam via intraperitoneal injec? tion, while N group was given a 0.05 mL/10 g dose of NS. Before administration and after 15, 30, 60 min of administration, the convulsion threshold of each group was measured. Results The count of autonomic activity of mice in A group was less than that of mice in D and N group during the 2nd day to 6th day(P<0.05). On the 1st and 7th day, the difference of the count of autonomic activity of mice between A group and the other two groups was not statistically significant(P>0.05). The convulsion threshold of mice in A group was higher than that of mice in D and N group before administration(P<0.05). Af?ter administration, the convulsion threshold of mice in N group didn’t show statistically significant difference from that of mice before administration(P>0.05). After 15 min of administration, the convulsion threshold of mice in D group was high?er than that of mice in A and N group(P<0.05), while the convulsion threshold of mice in A group was higher than that of mice in N group(P<0.05). After 30 min and 60 min of administration, both the convulsion thresholds of mice in A and D group were higher than that of mice in N group(P<0.05). However, at this point, the difference of the convulsion thresholds of mice between A and D group was not statistically significant(P>0.05). Conclusion Alcohol dependence has anticon?vulsant effect. Alcohol dependence weakens the anticonvulsant effect of diazepam.

OBJECTIVETo investigate the effects of fluorochloridone (FLC) exposure on the testes of adult Sprague-Dawley (SD) rats.

METHODSForty male SD rats were randomly divided into four groups. These groups, each of 10 male rats, were separately given FLC by gavage at a dose of 0 (control), 30, 150, or 750 mg/kg once daily for 28 d. The oxidative stress biomarkers in the testes were measured by spectrophotometry. The pathological changes in testicular tissues were evaluated under the light and electric microscopes. The cauda epididymal sperm count was determined. The testicular toxicity of FLC was assessed accordingly.

RESULTSCompared with the control group, the 750 mg/kg FLC group had significantly lower testicular weight and organ coefficient, epididymal weight, and cauda epididymal sperm count (P < 0.05 or P < 0.01), the 150 and 750 mg/kg FLC groups had significantly increased malonaldehyde content (P < 0.05 or P < 0.01), each exposed group had a significantly reduced glutathione (GSH) level (P < 0.05 or P < 0.01), the 750 mg/kg FLC group had significantly reduced activities of superoxide dismutase (SOD), catalase (CAT), GSH peroxidase, GSH S-transferase (GSH-ST), and GSH reductase (GSH-GR) (P < 0.05 or P < 0.01), the 150 mg/kg FLC group showed significant decreases in the activities of all antioxidant enzymes except GSH-GR (P < 0.05 or P < 0.01), and the 30 mg/kg FLC group showed significant decreases in the activities of SOD and CAT (P < 0.05 or P < 0.01). Furthermore, seminiferous epithelial degeneration, Sertoli cell vacuolization, spermatogenic cell loss, and nuclear damage were observed under the light and electronic microscopes in the 150 and 750 mg/kg FLC groups.

CONCLUSIONFLC could damage the testes of adult rats by inducting oxidative stress. This research provided clues and directions for further exploration of the mechanism of FLC testicular toxicity.

Animals ; Male ; Oxidative Stress ; drug effects ; Pyrrolidinones ; toxicity ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Testis ; drug effects ; metabolism ; pathology

Objective To determine the clinical value of hypergammaglobulinemia as a sentinel for autoimmune pancreatitis and avoid unnecessary pancreas resection.Methods All 14 patients with autoimmune pancreatitis or related pancreatic diseases underwent routine examinations,including liver function,CA199 and imaging.Measurement of serum IgG or IgG4 was performed for patients with clinically suspected or pathologically proved autoimmune pancreatitis.Clinical features were retrospectively compared between the AIP and non-AIP patients using x2 statistics with Yates correction or Fisher exact test.Results Ten cases were finally confirmed as autoimmune pancreatitis.All patients with autoimmune pancreatitis had elevated levels of serum γ-globulins,while only one case without autoimmune pancreatitis had elevated levels of serum γ-globulins.It was proved by subsequent antibody tests that serum IgG/IgG4 and γ-globulins were simultaneously increased.Conclusions Hypergammaglobulinemia can be used as a preoperative sentinel indicator for differentiating autoimmune pancreatitis from pancreatic malignancies and avoiding unnecessary pancreas operation.

Objective The development of cancer vaccines deserves experimentation,specifically the immunogenicity of the new MUC1 DNA vaccine for pancreatic cancer.Methods Three strategies were combined to optimize the new MUC1 DNA vaccine.The female C57BL/6 mice were immunized,through tibial muscle injection,with 100 μg of plasmid DNA of the recombinant plasmids (pIRES2-EGFP-3VNTR group,pIRES2-EGFP-3VNTR-C1-144 group,pIRES2-EGFP 3VNTR-mIL-18 group,pIRES2-EGFP-3VNTR-C1-144-mIL-18 group,n=5) for a total volume of 100 μl.Mice inoculated with the empty vector pIRES2-EGFP (EV group,n=5) and normal saline (NS group,n=5) were used as vector and blank controls,respectively.All the mice were immunized again every two weeks.Two weeks after the third immunization,all the mice were euthanized and spleen cells were separated for CTL cytotoxic assay.Results The specific cytolysis percentages of the four groups (pIRES2-EG-FP-3VNTR,pIRES2-EGFP-3 VNTR-C1-144,pIRES2-EGFP-3VNTR-mIL-18,pIRES2-EGFP 3VNTR-C1-144-mIL-18) expressing VNTR were higher than the EV and NS group with the effector/target cells ratio (E/T) from 80:1 to 20:1 (P＜0.05).Therefore,it showed a difference among the four groups.After the primary immunization,the OD450 of the serum antibody level specific to MUC1 began to increase in the four groups which contained the gene of VNTR3 (P＜0.05).This suggests that the recombinant plasmids could induce a specific antibody response to MUC1,and showed no remarkable difference among the four groups.IFN-γ serum cytokine among the four groups were higher than that of the EV and NS groups (P＜0.05).There was a significant difference of OD450 between the groups containing mIL-18 pIRES2-EGFP-3VNTR-mIL-18,pIRES2-EGFP-3VNTR-C1-144-mIL-18) and those not (pIRES2-EGFP-3VNTR,pIRES2-EGFP-3VNTR-C1-144,)(P＜0.05).Conclusions In conclusion,all of the four recombinant plasmids could induce MUC1 specific CTL and antibodies responses,and C1-144 and IL-18 could enhance the immunogenicity of plasmids.