Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatectomy ; Prostatic Neoplasms ; blood ; metabolism ; radiotherapy ; surgery

OBJECTIVE: To investigate the effect of Salvia Miltiorrhiza injection (SMI) on peritoneal dialysis solution (PDS) induced injuries of peritoneal structure and function in a rat model, and to observe the relationship between the failure of peritoneal dialysis and expressions of aquaporin-1 (AQP-1) and zonula occluden-1 (ZO-1) in peritoneal tissues. METHODS: Fifty-six SD rats were randomly divided into normal control group, 1.5% PDS group, 4.25% PDS group, 1.5%PDS+1% SMI group, 1.5%PDS+2% SMI group, 4.25% PDS+1% SMI group and 4.25% PDS+2% SMI group. Two-hour peritoneal dialysis test was performed in rats in different groups by intraperitoneal injection for 8-week. Then rats were killed on the 8th week, and the bloods and peritoneal tissues were gathered. The rate of ultrafiltration, clearance rates of urea nitrogen, creatinine and glucose of peritoneum and content of total protein in PDS were detected. Peritoneal membrane histology was evaluated by light microscopy and transmission electron microscopy. Expressions of ZO-1 and AQP-1 proteins in peritoneal tissues were detected by immunohistochemical method, and AQP-1 protein expression was also detected by Western blotting technique. RESULTS: Compared with normal control group, using of 1.5% PDS and 4.25% PDS caused the changes of structure and function in peritoneum, such as pathological change of peritoneum, decreasing of the rate of ultrafiltration (P<0.05), clearance rates of creatinine and glucose (P<0.01) and the expression of ZO-1 protein (P<0.05), and increasing of the expression of AQP-1 protein (P<0.05). Compared with the simple PDS groups, the pathological damage of peritoneum was lessened and the rate of ultrafiltration and clearance rates of creatinine and glucose were increased in the 1.5% PDS+2% SMI group and 1.5% PDS+2% SMI group. Expression of AQP-1 protein was decreased by 1.5% PDS+2% SMI as compared with 1.5% PDS (P<0.05).[JP] CONCLUSION: SMI can relieve the injuries of function and structure of peritoneum by down-regulating the expression of AQP-1 protein.

Objective To observe the effect of Huangqi (Radix Astragali seu Hedysari) Injectio on the abnormal expression of aquaporin-1 (AQP-1) caused by glucose lactate peritoneal dialysis solution. Methods Different glucose concentration lactate peritoneal dialysis solutions and Huangqi Injectio given to the rats intraperitoneally. Eight weeks later, the ultrafiltration of peritoneal dialysis, peritoneum clearance, peritoneal structure, AQP-1 and its gene expression were observed. Results Compared with the control group, in the glucose and Huangqi groups, the ultrafiltration of peritoneal dialysis was remarkably decreased (P

Child ; Electroacupuncture ; adverse effects ; instrumentation ; Electrolysis ; Equipment Failure ; Equipment and Supplies ; adverse effects ; Humans ; Male

AIM:To investigate the clinical effect of panretinal photocoagulation (PRP) combined with calcium dobesilate in treatment of diabetic retinopathy (DR).METHODS:Selected 120 cases (240 eyes) of DR diagnosed in our hospital from January 2011 to January 2016 were retrospectively analyzed.According to whether calcium dobesilate was used, the treatment group was divided into two groups.Sixty cases were treated with PRP combined with calcium dobesilate, and 60 cases in the control group were treated with PRP only.The BCVA, CMT and clinical efficacy of the two groups were compared.RESULTS:Before treatment, there was no significant difference on BCVA between combined group and control group (P>0.05).After treatment, BCVA of combined group was higher than that of the control group (P<0.01).Before the treatment, no statistically significant difference between combined group and control group on CMT, neovascularization and fluorescein leakage area were found (P>0.05);after treatment, the combination group on CMT, neovascularization and fluorescein leakage area value were less than the control group (P<0.01).After treatment, combined group was appearance effect in 65.0%, effective in 30.0%, invalid in 5.0%, the control group was 50.8%, effective 36.7%, invalid 12.5%, all statistically significant differences between the two groups (P<0.05).CONCLUSION:PRP combined with calcium dobesilate in treatment of DR has a more significant clinical effect than PRP alone.

The purpose of many microarray studies is to find the association between gene expression and sample characteristics such as treatment type or sample phenotype.There has been a surge of efforts developing different methods for delineating the association. Aside from the high dimensionality of microarray data, one well recognized challenge is the fact that genes could be complicatedly inter-related, thus making many statistical methods inappropriate to use directly on the expression data. Multivariate methods such as principal component analysis (PCA) and clustering are often used as a part of the effort to capture the gene correlation, and the derived components or clusters are used to describe the association between gene expression and sample phenotype. We propose a method for patient population dichotomization using maximally selected test statistics in combination with the PCA method, which shows favorable results. The proposed method is compared with a currently well-recognized method.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

OBJECTIVETo observe the vasodilating effect of adrenomedullin 2 (ADM2) by antagonizing angiotensin 1 (Ang II), and to explore its mechanism.

METHODSEighteen male, 180-200 g SD rats were randomly divided into 3 groups (n = 6): control group, Ang II (150 ng/(kg x min)) group and Ang II (150 ng/(kg x min)) + ADM2(500 ng/(kg x h)) group. Mini-osmotic pumps filled with peptide were implanted in the back of rats subcutaneously. After two weeks, the blood pressure was measured by the way of carotid intubation. The plasma was collected for the detection of nitric oxide (NO) content and the activity of endothelial nitric oxide synthase (eNOS). The in situ oxidation of fluorescent dye dihydroethidium (DHE) was used for detecting superoxide in rat arteries. The rat isolated arterial rings were made for studying the vasodilating effect of ADM2. Human umbilical vein endothelial cell line EA. hy 926 cells were cultured and their intracellular reactive oxygen species (ROS) were evaluated by probe DCFH-DA.

RESULTSADM2 dramatically decreased the blood pressure in angiotensin II-induced hypertension rat model, enhanced plasma NO content and the activity of eNOS and reduced superoxide formation in vessel walls. ADM2 also induced relaxation of the vascular rings preconstricted by Ang II in a concentration-dependent and endothelium-dependent manner. In cultured vascular endothelium, ADM2 ameliorated the ROS generation induced by Ang II.

CONCLUSIONAdrenomedullin 2 relaxed blood vessels by antagonizing angiotensin II-induced oxidative stress and improving the vascular endothelial function.

Adrenomedullin ; pharmacology ; Angiotensin II ; pharmacology ; Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; Drug Antagonism ; Endothelium, Vascular ; drug effects ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Male ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; blood ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Vasodilation ; drug effects

Biopsy, Fine-Needle ; China ; Cytodiagnosis ; methods ; Cytological Techniques ; methods ; Esophageal Neoplasms ; pathology ; Humans ; Neoplasms ; pathology ; Pathology, Clinical ; methods

OBJECTIVETo observe effects of treatment from the lung and treatment from the intestine on the level of vasoactive intestinal peptide (VIP) in the lung and intestine of ulcerative colitis (UC) rats.

METHODSThe UC rat model was established in 52 rats by using rabbit intestine mucosa tissue allergen combined TNBS-ethanol model (with the model successful rate of 78.0%). Eight rats randomly selected from 40 successfully modeled rats and 8 of 16 rats from the normal group were recruited as the model group and the normal control group before intervention (at week 0). The rest 32 successfully modeled rats were randomly divided into the model group, the Western medicine treatment group (salazosulfapyridine), the treatment from lung group (Huangqi Jiegeng Decoction), and the treatment from intestine group (Huangqi Huanglian Decoction), 8 in each group. Rats in each treatment group were administered with corresponding medication 8 times the dose of a 60 kg adult human. Another 8 normal rats were recruited as the normal group. Equal volume of pure water was given to rats in the model group and the normal group by gastrog avage, once per day. Contents of VIP in the lung tissue and the intestinal tissue were detected at week 0 and 4 after 4-week consecutive intervention. Pathomorphological changes of the lung tissue and the colon tissue were observed under light microscope.

RESULTSCompared with the normal control group at week 0, evenly distributed diffuse inflammation could be seen in the pulmonary interstitial tissue; the bronchial wall was thickened; a huge amount of infiltration surrounded bronchi and blood vessels; a large area of necrosis of intestinal mucosa and inflammatory cell infiltration could also be seen in the model group. Pathological injuries of the lung and the colon were more alleviated in each treatment group than in the model group at the same time point. Compared with the normal control group at the same time point, VIP contents in the lung tissue significantly decreased in the model group at the end of week 4 (P<0.05); VIP contents in the colon tissue significantly increased in the model group at the end of week 0 and 4 (P <0.05). Compared with the model group, VIP contents in the lung tissue significantly increased in the Western medicine treatment group and the treatment from lung group at the end of week 4 (P<0.01); VIP contents in the colon tissue significantly decreased in the treatment from lung group and the treatment from intestine group (P<0.05, P<0.01).

CONCLUSIONTreatment from the lung and treatment from the intestine showed predominant advantage in improving local inflammation of the lung and the intestinal tract, alleviating pathological injuries, promoting repair of injuries through regulating VIP contents in the lung tissue and the colon tissue.

Animals ; Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Intestinal Mucosa ; metabolism ; Intestines ; Lung ; Male ; Rabbits ; Rats ; Vasoactive Intestinal Peptide