Objective To investigate the clinical and pathological characteristics of kidney disease by renal biopsy,thus to provide reference and help for the application of renal biopsy in the diagnosis and treatment of kidney diseases. Methods From January 2015 to June 2017,136 cases with kidney disease in Zhoushan Hospital were slected in the research. All patients received renal biopsy,histochemical staining of renal biopsy samples,immunohistochemical staining,and observed under light microscope, and the pathological changes of the situation, combined with clinical data,the clinical and pathological characteristics of renal biopsy patients were summarized. Results The distribution of pathological type of primary glomerulonephritis,the highest proportion (79. 41％),secondary glomerulonephritis (15. 44％),followed by the rest of the renal tubular and interstitial nephropathy (5. 15％). Of the primary glomerulo-nephritis,membranous nephropathy ( 28. 68％), IgA nephropathy ( 27. 94％) accounted for a relatively high proportion. However,in secondary glomerulonephritis,diabetic nephropathy (5. 88％) was the highest proportion. Of gender,the proportion of the male patients (59. 56％) was higher than that of the female patients (40. 44％,χ2 =9. 941,P<0. 05),primary glomerulonephritis in the male patients(62. 04％) was higher thanthat in the female patients (37. 96％) (χ2 =12. 519,P<0. 05). The age of renal biopsy was focused on the age of 41-50 years,>50-60 years,>60 -70 years old, which was mainly the elderly population. Conclusion Renal biopsy of kidney disease is mainly primary glomerulonephritis,the incidence of people mainly in the elderly male population. Compre-hensive diagnosis is needed for different kidney diseases with renal biopsy and the specific circumstances.

Objective: To analyze the effect of cardiac resynchronization therapy (CRT) in patients with chronic heart failure (CHF) combining left bundle branch block (LBBB) conformed to new diagnostic standard. Methods: A total of 19 CHF patients who received CRT in our hospital from 2005-06 to 2013-05 were studied. The patients were divided into 2 groups: True LBBB group,n=13 patients conformed to new diagnostic standard and False LBBB group, n=6 patients conformed to traditional diagnostic standard. Pre- and Post-operative LVEF, LVEDD, QRS duration (QRSd) and IVMD were compared in all patients; post-operative LVEF, LVEDD, QRSd, IVMD and Tmsv16-SD, Tmsv16-Dif were compared between 2 groups. Results: The post-operative LVEF, LVEDD, QRSd and IVMD were improved than pre-operative condition in both groups. Compared with False LBBB group, the improvements were more obvious in True LBBB group as LVEDD by mm (5.95±0.72 vs 7.13±0.78), IVMD by ms (22.45±8.00 vs 27.63±13.09), and QRSd by ms (140.38±5.80 vs 153.68±14.38), all P<0.01. The post-operative LVEF and Tmsv16-SD, Tmsv16-Dif were similar between 2 groups. Conclusion: CHF patients combining either true or false LBBB could be beneift from CRT, while the patients with true LBBB may receive better clinical outcomes from CRT.

Objective To evaluate the feasibility, efficacy and safety of new nano material occluder of single rivet type (left-disk with no-hub) in treating ventricular septal defect (VSD) in order to provide experimental basis for clinical application. Methods A total of 26 healthy adult dogs were selected for this study . Under thoracotomy , VSD model was established through fluoroscopically-guided percutaneous puncturing of the right ventricular free wall. The models were randomly and equally divided into the study group(n=13, using nano material VSD occluder) and the control group(n=13, using double-hub nitinol occluder). Every two dogs from each group were sacrificed each time at one, 2, and 3 months after percutaneous closure of VSD with corresponding occluder, the tissue samples were collected and sent for gross examination as well as for the optical and electronic microscopy study;the blood concentration of nickel ion was also determined. The state of endothelialization after implantation of the new type occluder was evaluated, and the complications such as residual shunt and superficial thrombus formation were recorded. The results were analyzed. Results By open chest operation with small incision and percutaneous puncturing of the right ventricular free wall, VSD model was successfully established in all 26 dogs. The success rate of the implantation of the VSD occluder in the study group was 100%, while it was 91.7% in the control group. One, 2, 3 and 6 months after the implantation, the heart specimens of 25 dogs were removed and gross examination showed that neither occluder displacement nor alloy wire fracture occurred in both groups. No thrombus formation or vegetation attached on the disk surface was observed. One month after the procedure , in the study group the bilateral disk surfaces of the occluder were covered with thin layer transparent tissue , which were proved to be composed of the fibrous tissue and endothelial cells through pathologic and electronic microscopy study. Six months after implantation, the superficial tissue of the occluder became further thickened and the occluder edge became fused with the surrounding heart tissue. Conclusion The design of the new VSD nano materials occluder, which has a left-disk with no hub, is very scientific. Compared with double-hub nitinol occluder, the new device can shorten the time of complete endothelialization and effectively occlude the VSD. Therefore, this new nano material occluder has promising prospect in clinical application.

Local medical college is the mainstream of altitude medical college education in our country.Facing furious competition,we must make a reasonable orientation,construct the characteristics of running school,establish scientific concept,construct specific subject and specialty and make an all-around development in order to walk up to national stage by depending on powerful unity,serve the regional economy and social development,and form a new situation of two patterns by converting single medical colleges to all-around college and remaining the existing single medical college.

Objective To investigate the relationship between nutritional risk status and implementation of nutrition therapy in mechanical ventilated (MV) chronic obstructive pulmonary disease (COPD) patients, so as to provide evidence for individualized nutrition therapy. Methods A prospective multicenter observational study was conducted. MV COPD patients admitted to Department of Intensive Care Units (ICU) of 10 County Hospitals in Zhejiang Province from January 2015 to January 2016 were enrolled, and according to nutrition risk screening 2002 (NRS2002) score, they were divided into nutritional high risk group (NRS2002 3-5) and nutritional extremely high risk group (NRS2002 6-7). Nutrition therapy situation and hospital mortality were compared between the two groups; multivariate Cox regression analysis was used to analyze the risk factors affecting the prognosis of patients with COPD under mechanical ventilation. Kaplan-Meier curve was used to analyze the prognosis at 30 days; receiver operating characteristic (ROC) curve was used to test the robustness of multivariable regression analysis. Results ① One hundred and six COPD patients with MV were analyzed; among them, 90 patients were in the nutritional high risk group, and 16 were in the nutritional extremely high risk group. There were no significant differences in age, gender and body mass index (BMI) between the two groups (all P > 0.05); the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, NRS2002 score in patients of nutrition risk extremely high group were obviously higher than that in patients with nutrition high risk group (APACHEⅡ: 24.9±6.1 vs. 20.3±5.8, NRS2002 score: 6.3±0.5 vs. 4.2±0.8, both P < 0.05). ② Patients in both groups received early enteral nutrition (EN) therapy, the proportion of patients in nutritional extremely high risk group received early EN was lower than that of patients in the nutritional high risk group [12.5% (2/16) vs. 17.7% (16/90)], along with the prolongation of hospital stay, the proportions of patients beginning to receive the EN were gradually increased in the nutrition extremely high risk group and high risk group, after 2 days the EN increased significantly, and reached the highest value on day 6 after entering ICU [100.0% (16/16), 98.9% (89/90), respectively]; within 3 days after admission into ICU, the proportion of EN in nutrition extremely high risk group was obviously lower than that in nutrition high risk group, and from day 4, there was no statistical significant difference in proportion of EN between the two groups (all P > 0.05). The time to start parenteral nutrition (PN) treatment was relatively early admission to the ICU on day 1 and the proportion of this therapy was high in the two groups [56.2% (9/16), 27.7% (25/90), respectively], the PN proportion did not decrease with the length of hospitalization and the increase of EN. The proportion of patients in the nutrition extremely high risk group who started PN treatment was higher, which reached 56.2% admission to the ICU on day 1.③ With extension of hospital stay, the calories of EN were gradually increased in the nutritional high risk group, the highest calories in nutritional high risk groups was 4 318 (3 912, 4 812) kJ/d at day 7; while the highest calories in nutritional extremely high risk groups was 3 602 (2 167, 4 615) kJ/d at day 6 and a slight decreased at day 7; the difference of calories within the first week between the two groups had no significance (all P > 0.05). The calorific value of PN therapy remained at a constant level during hospitalization within 7 days, and after admission into ICU for 4-5 days, the target range of calories was achieved. ④ Kaplan-Meier survival curve analysis showed that the mortality at 30 days in the extremely high risk group was significantly higher than that in the high risk group [62.5% (10/16) vs. 11.1% (10/90), χ2 = 15.4, P < 0.01]. ⑤ Multiple cox-regression analysis showed that NRS2002 scoring was the independent risk factor affecting the mortality of patients in hospital [odds ratio (OR) = 2.08, 95% confidence interval (95%CI) = 1.39-3.12, P = 0.005]. ⑥ ROC curve analysis: according to ROC curve analysis of the effectiveness of multi-factor regression model, area under ROC curve (AUC) was 0.79, sensitivity was 70.00%, specificity was 74.42%, positive likelihood ratio was 2.74, negative likelihood ratio was 0.40, 95% confidence interval (95%CI) was 0.702-0.864, P = 0.001, and it showed that the regression model had a good prediction effect. Conclusions MV COPD patients have significant nutritional risk and all receive early EN therapy. The proportion of beginning to use PN treatment in patients with nutritional extremely high risk is relatively high. Initial nutritional status is the independent risk factor of poor prognosis in MV patients with COPD.

Objective:To investigate the role and mechanism of sodium valproate (VPA) in cardiac and cerebral injuries after cardiopulmonary resuscitation (CPR) in pigs.Methods:Twenty-five healthy male domestic pigs, weighing (37±3) kg, were randomly divided into the sham group ( n=6), CPR group ( n=10), and CPR+VPA group ( n=9). Cardiac arrest was induced by alternating current delivered via a pacing catheter in the right ventricle and untreated for 9 min, and then CPR was performed for 6 min, in which this procedure was used to establish the animal model of cardiac arrest and CPR. At 5 min after resuscitation, a dose of 150 mg/kg of VPA was infused with a pump via the femoral vein in 1 h in the CPR+VAP group. At 1 h, 2 h, 4 h and 24 h after resuscitation, blood samples were drawn from the femoral vein, and then used to measure the serum concentrations of cardiac troponin I (cTnI), creatine kinase MB (CKMB), neuron specific enolase (NSE), and S100B protein (S100B) by ELISA. At 24 h after resuscitation, the animals were euthanized, and then tissue specimens in the left myocardium and brain cortex were rapidly harvested to detect the expression levels of C/EBP homologous protein (CHOP), caspase 12, and caspase 3 by Western blot, and the rate of apoptotic cells was detected by TUNEL. Continuous variables were compared with one way analysis of variance among the three groups. Results:(1) After resuscitation, cardiac and cerebral injury biomarkers including cTnI, CKMB, NSE, and S100B in serum were significantly increased in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). The serum concentrations of cTnI and NSE starting 1 h after resuscitation and the serum concentrations of CKMB and S100B starting 2 h after resuscitation were significantly decreased in the CPR+VPA group compared to the CPR group (all P<0.05). (2) Those proteins related to cell apoptosis mediated by endoplasmic reticulum stress, including CHOP, caspase 12, and caspase 3, were significantly increased, and meanwhile apoptosis index was markedly elevated after resuscitation in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). Nevertheless, the expression levels of CHOP, caspase 12, and caspase 3 were significantly decreased, and cell apoptosis was markedly reduced in the heart and brain after resuscitation in the CPR+VPA group compared to the CPR group (all P<0.05). Conclusions:VPA can alleviate cardiac and cerebral injuries after CPR in pigs, and its mechanism may be possibly related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8⁺ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8⁺ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Animals ; Mice ; Lipid Droplets ; Autophagy ; Autophagosomes ; Homeostasis ; Triglycerides