Objective:To unveil the pathological changes associated with demyelination in schizophre-nia(SZ)and its consequential impact on interstitial fluid(ISF)drainage,and to investigate the thera-peutic efficacy of ursolic acid(UA)in treating demyelination and the ensuing abnormalities in ISF drainage in SZ.Methods:Female C57BL/6J mice,aged 6-8 weeks and weighing(20±2)g,were randomly divided into three groups:control,SZ model,and UA treatment.The control group received intraperitoneal injection(ip)of physiological saline and intragastric administration(ig)of 1％carboxy-methylcellulose sodium(CMC-Na).The SZ model group was subjected to ip injection of 2 mg/kg dizo-cilpine maleate(MK-801)and ig administration of 1％CMC-Na.The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801.The treatment group received UA pretreatment via ig administration for one week,followed by a two-week drug intervention for all the three groups.Behavioral assessments,including the open field test and prepulse inhibition experiment,were conducted post-modeling.Subsequently,changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions.Immunofluorescence analysis was employed to examine alterations in aquaporin 4(AQP4)polarity distribution in the brain and changes in protein expres-sion.Myelin reflex imaging using Laser Scanning Confocal Microscopy(LSCM)was utilized to study modifications in myelin within the mouse brain.Quantitative data underwent one-way ANOVA,followed by TukeyHSD for post hoc pairwise comparisons between the groups.Results:The open field test re-vealed a significantly longer total distance[(7 949.39±1 140.55)cm vs.(2 831.01±1 212.72)cm,P＜0.001]and increased central area duration[(88.43±22.06)s vs.(56.85±18.58)s,P=0.011]for the SZ model group compared with the controls.The UA treatment group exhibited signifi-cantly reduced total distance[(2 415.80±646.95)cm vs.(7 949.39±1 140.55)cm,P＜0.001]and increased central area duration[(54.78±11.66)s vs.(88.43±22.06)s,P=0.007]compared with the model group.Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the star-tle reflex in the model group relative to the controls(P＜0.001 for both),with the treatment group dis-playing significant improvement(P＜0.001 for both).Myelin sheath analysis indicated significant demy-elination in the model group,while UA treatment reversed this effect.Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thala-mus in the model group relative to the controls[(13.93±3.35)mm2 vs.(2.79±0.94)mm2,P＜0.001 for diffusion area;(2.48±0.38)mm2 vs.(0.05±0.12)mm2,P＜0.001 for reflux area],with sig-nificant impairment of drainage in brain regions.The treatment group demonstrated significantly reduced tracer diffusion and reflux areas[(7.93±2.48)mm2 vs.(13.93±3.35)mm2,P＜0.001 for diffusion area;(0.50±0.30)mm2 vs.(2.48±0.38)mm2,P＜0.001 for reflux area].Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls[(3 663.88±733.77)μm2 vs.(13 354.92±4 054.05)μm2,P＜0.001].The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression[(11 104.68±3 200.04)μm2 vs.(3 663.88±733.77)μm2,P＜0.001].Conclusion:UA intervention ameliorates behavioral performance in SZ mice,Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function.The underlying mechanism may involve the improve-ment of demyelination and ISF drainage dysregulation in SZ mice.

Objective To investigate the effect of ophiopogonin B(OP-B)on tumor growth in gastric tumor-bearing rats and its underlying mechanism.Methods Sixty-six SPF SD rats(half male and female,6 weeks old,180～200 g)were randomly divided into model group,low-,medium-and high-dose OP-B groups,and activator group,with 10 rats in each group.The gastric tumor-bearing model was established by orthotopic transplantation of Walker-256 tumor tissue.The rats in the 3 doses groups were given 17.5,35 and 70 mg/kg OP-B,respectively,by gavage and intraperitoneal injection of the same amount of normal saline,and the rats in the activator group were intragastrically administered with 70 mg/kg OP-B and intraperitoneally injected with 1 mg/kg Rho A/ROCK1 signaling pathway activator,lysophosphatidic acid(LPA).The weight and volume of transplanted tumor were recorded to calculate the tumor inhibitory rate.The morphology of tumor tissue was observed with HE staining.The apoptosis of tumor cells were detected by TdT-mediated dUTP-biotin nick end labeling(TUNEL)staining.The expression of proliferating cell nuclear antigen 67(Ki-67)and cleavage cysteine aspartic acid proteolytic enzyme-3(Cleaved Caspase-3)in tumor tissues were detected by immunohistochemical staining.RT-qPCR and Western blotting were utilized to measure the expression of Ras homologous gene family member A(Rho A)and Rho-associated coiled-coil forming protein kinasel(ROCK1)at mRNA and protein levels.Results Compared with the model group,the tumor weight and volume,mRNA and protein levels of Ki-67,Rho A and ROCK1 were significantly decreased,and the tumor inhibitory rate,tumor cell apoptotic rate and Cleaved Caspase-3 protein level were obviously increased in the low-,medium-and high-dose OP-B groups(P＜0.05).The activator group had heavier tumor weight and larger volume,increased mRNA and protein expression levels of Ki-67,Rho A and ROCK1,and lower tumor inhibitory rate and apoptotic rate and reduced Cleaved Caspase-3 expression when compared with the high-dose OP-B group(P＜0.05).Conclusion OP-B may suppress the tumor growth of gastric tumor-bearing rats by inhibiting the activation of Rho A/ROCK1 signaling pathway.

Objective To investigate the factors influencing the prognosis of complex intracranial aneurysms treated with pipeline flow-directed device(PED)and to develop a nomogram prediction model.Methods The clinical data of a total of 98 patients with complex intracranial aneurysm,who were admitted to the Anyue County People's Hospital or the Second Affiliated Hospital of Guilin Medical College of China from January 2021 to April 2023 to receive PED treatment,were retrospectively analyzed.The influencing factors that might affect the prognosis of patients with complex intracranial aneurysm were collected.According to the modified Rankin Scale(mRS)score,the patients were divided into good prognosis group(being defined as mRS ≤2 points)and poor prognosis group(being defined as mRS＞2 points).The clinical data were compared between the two groups,and a nomogram model was established and validated.Results In the 98 patients,poor prognosis was seen in 10(10.20％).The differences in age,history of hypertension,history of diabetes mellitus,clopidogrel resistance,Fisher classification,repeated aneurysm rupture,aneurysm location,aneurysm size,aneurysm neck,multiple lesions,and Hunt-Hess grade on admission between good prognosis group and poor prognosis group were statistically significant(all P＜0.05).Multivariate analysis revealed that history of hypertension,clopidogrel resistance,repeated aneurysm rupture,aneurysm location,multiple lesions,and Hunt-Hess grade were the independent factors influencing the prognosis of patients with complex intracranial aneurysm after receiving PED treatment.The AUC of the nomogram model in predicting the prognosis of PED for complex intracranial aneurysms was 0.849(95％CI=0.758-0.939).The predicted curves of the model group and validation group were basically fitted to the standard curves.The results of the decision curve analysis showed that the net benefit to patients was greater than 0 when the probability threshold of the nomogram model for predicting a poor prognosis of PED for complex intracranial aneurysms was 0.10-0.90.Conclusion The factors causing poor prognosis of PED for complex intracranial aneurysms mainly include history of hypertension,clopidogrel resistance,repeated aneurysm rupture,etc.The nomogram model established in this study can predict the risk of poor prognosis in patients with complicated intracranial aneurysm after receiving PED treatment.

[This corrects the article DOI: 10.1016/j.jpha.2021.06.007.].

GB7 acetate is a galbulimima alkaloid obtained from Galbulimima belgraveana.However,information regarding its structure,biological activities,and related mechanisms is not entirely available.A series of spectroscopic analyses,structural degradation,interconversion,and crystallography were performed to identify the structure of GB7 acetate.The MTT assay was applied to measure cell proliferation on human colorectal cancer HCT 116 cells.The expressions of the related proteins were measured by Western blotting.Transmission electron microscopy(TEM),acridine orange(AO)and monodansylcadaverine(MDC)staining were used to detect the presence of autophagic vesicles and autolysosomes.A transwell assay was performed to demonstrate metastatic capabilities.Oxygen consumption rate(OCR)and extracellular acidification rate(ECAR)assays were performed to determine the mitochondrial oxidative phosphorylation(OXPHOS)and glycolysis activity of HCT 116 cells.The data showed that GB7 acetate suppressed the proliferation and colony-forming ability of HCT 116 cells.Pretreatment with GB7 acetate significantly induced the formation of autophagic vesicles and autolysosomes.GB7 acetate upregulated the expressions of LC3 and Thr172 phosphorylated adenosine 5'-monophosphate(AMP)-activated pro-tein kinase α(p-AMPKα),which are key elements of autophagy.In addition,GB7 acetate suppressed the metastatic capabilities of HCT 116 cells.Additionally,the production of matrix metallo-proteinase-2(MMP-2)and MMP-9 was reduced,whereas the expression of E-cadherin(E-cad)was upregulated.Furthermore,GB7 acetate significantly reduced mitochondrial OXPHOS and glycolysis.In conclusion,the structure of the novel Galbulimima alkaloid GB7 acetate was identified.GB7 acetate was shown to have anti-proliferative,pro-autophagic,anti-metastatic,and anti-metabolite capabilities in HCT 116 cells.This study might provide new insights into cancer treatment efficacy and cancer chemoprevention.

OBJECTIVE：To provide reference for the c onstruction of subject diagnosis and treatment scheme in drug clinical trials. METHODS ：The subject diagnosis and treatment module was developed and implemented in our hospital on the basis of CTMS，and its effects were evaluated. RESULTS ：A subject diagnosis and treatment module was established in CTMS of our hospital. Within one year from the launch of the module in the middle of October ，2019，the overall number of subjects in the group showed an increasing trend ，and the overall mean dropout rate of subjects was 0.16％. The data interface of CTMS system ， hospital information system （HIS），laboratory information management system ，medical imaging information system had been established，so as to realize the synchronization of subject information （displaying subject identification in HIS system ）and the interaction of diagnosis and treatment information and billing data （patients and subjects were charged separately ）. Since the launch of the module ，the amount of data generated by the interface had been increasing ，and the number of departments producing the subject diagnosis and treatment business had been increasing month by month. Compared with subject diagnosis and treatment project based on HIS system ，the number of subject diagnosis and treatment business based on CTMS system was increased significantly（P＜0.05）. CONCLUSIONS ：The subject diagnosis and treatment module based on CTMS improves the efficiency of subject diagnosis and treatment project implementation and financial settlement ，and realizes the efficient implementation of drug clinical trial projects in large general hospitals.

Objective:To evaluate the efficacy and safety of lactulose combined with polyethylene glycol for bowel preparation before colonoscopy in patients of different risks.Methods:A total of 208 patients undergoing colonoscopy were enrolled, including 108 high-risk and 100 low-risk patients. The high-risk patients were divided into group A (54 taking lactulose + polyethylene glycol) and group B (54 taking polyethylene glycol), and the low-risk patients were divided into group C (49 taking lactulose + polyethylene glycol) and group D (51 taking polyethylene glycol). The Boston bowel preparation score, cecal intubation time, withdrawal time, the detection rate of colonic polyps and adenoma, and the incidence of adverse reactions were observed.Results:Among the high-risk patients, the Boston bowel preparation score and adenoma detection rate in group A [(6.35±1.15) scores, 46.3%] were significantly higher than those in group B [(5.76±0.89) scores, 22.2%, both P<0.05], and the first defecation interval in group A was significantly shorter than that in group B [(1.20±0.85) h VS (3.29 ± 2.93) h, P<0.05]. There was no significant difference in adequate bowel preparation rate, polyp detection rate, frequency of defecation or incidence of adverse reactions between group A and B. In the low-risk patients, the first defecation interval in group C was significantly shorter than that in group D [(1.65 ± 1.35) h VS (3.42 ± 2.64) h, P<0.05], and the incidence of adverse reactions was significantly lower than that in group D (44.9% VS 64.7%, P<0.05). There was no significant difference in adequate bowel preparation rate, Boston bowel preparation score, adenoma detection rate, polyp detection rate or frequency of defecation between group C and D. Conclusion:For the high-risk patients, the effect of lactulose combined with polyethylene glycol for bowel cleansing is better than that of traditional polyethylene glycol in the improvement of the Boston bowel preparation score, adenoma detection rate, and the first defecation interval. For low-risk patients, lactulose combined with polyethylene glycol regimen has few advantages over traditional polyethylene glycol regimen.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

Objective:To establish an air-pouch bladder cancer (APBCa) model and investigate whether it could be a new animal model to evaluate the efficacy of intravesical therapy through chemotherapeutics and BCG instillation.Methods:Filtered sterile air was injected subcutaneously into the backs of BALB/c Nude mice to create a 2.5 cm×3.5 cm air pouch. After 24 hours, human bladder cancer cells EJ were seeded on the inner face of the pouch wall to establish APBCa of human cancer (H-APBCa). Gemcitabine instillation was used to investigate whether chemotherapy could inhibit tumor growth in the H-APBCa model, and Tunel staining was used to verify the apoptosis of tumor cells 20-day treatment. Filtered sterile air was injected subcutaneously into the backs of C57BL/6 mice to create a 2.5 cm×3.5 cm air pouch. After 24 hours, mice bladder cancer cells MB49 were seeded on the inner face of the pouch wall to establish APBCa with intact immunity (I-APBCa). BCG instillation was used to investigate whether BCG could inhibit tumor growth in the APBCa model. Immunofluorescence was used to verify the infiltration of immune cells after 20-day treatment.Results:H-APBCa and I-APBCa mice models could be established by immune deficiency and intact mice. At day 20, chemotherapeutic instillation therapy could inhibit tumor growth (781.02±241.02 vs. 1213.88±214.02 mm 3, P<0.05) by inducing tumor cell apoptosis with statistically significant differences (77.33±4.63 vs. 14.67±2.60, P<0.05). BCG instillation was able to inhibit tumor growth (645.02±156.63 vs. 948.84±221.76, P<0.05) by increasing CD80 + macrophage (49.67±7.57 vs. 16.33±5.69, P<0.05) and T cells in the tumor with statistically significant differences (18.00±3.46 vs. 4.67±1.45, P<0.05). Conclusions:APBCa model could evaluate the efficacy of drug instillation and was expected to be a new animal model for studying drug for intravesical therapy.

Objective:To investigate the biocompatible properties of tissue-engineered rabbit trachea treated by Triton-X 100 processed method (TPM) and detergent enzymatic method (DEM) with genipin cross-linking.Methods:TPM and DEM were used to decellularize New Zealand rabbit trachea, and then genipin was used for cross-linking. The mechanical properties of each tracheal sample were measured by universal tensile testing machine. The structure of the sample was observed by scanning electron microscope. The cytotoxicity of the sample was detected by cell contact toxicity assay. Fifteen healthy adult New Zealand rabbits with no specific pathogens were divided into the native tracheal transplantation group, the genipin cross-linked TPM acellular tracheal matrix transplantation group and the genipin cross-linked DEM acellular tracheal matrix transplantation group according to the random number table, 5 animals for each group. Animals in each group were sacrificed 30 days after transplantation, and graft samples were obtained. The microstructure was observed by hematoxylin-eosin staining and CD68 molecular immunohistochemical staining.Results:Biomechanical results showed that the mechanical properties of decellularized tracheas with genipin cross-linking were similar to native tracheas. The results of scanning electron microscopy showed that the matrix of cross-linked decellularized tracheas was more dense comparing with native tracheas, and the mesh-like ultrastructure formed on the outer surface of the genipin cross-linked DEM acellular tracheal matrix was conducive to cell adhesion. The results of cell contact toxicity results showed that the genipin cross-linked decellularized tracheas treated by DEM had better biocompatibility. The results of in vivo implantation and histological staining showed that genipin cross-linked DEM acellular tracheal matrix was less immunogenic comparing with genipin cross-linked TPM acellular tracheal matrix.Conclusions:Genipin can improve the ultrastructure of decellularized tracheal matrix without causing inflammatory. The genipin cross-linked decellularized tracheas treated by DEM has better biocompatibility and lower immunogenicity, which make it suitable for the replacement of tissue engineering trachea.