Recently, photodynamic therapy (PDT) has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis. Unfortunately, the activation of high mobility group box 1 protein (HMGB1) by PDT triggers innate and adaptive immune responses, which exacerbate skin inflammation. Herein, we combined glycyrrhizic acid (GA), a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch., with PDT actuated by the photosensitizer chlorin e6 (Ce6) by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt (GC NPs/QCS-C). GC NPs/QCS-C exhibited high drug loading efficacy, uniform size distribution, an ideal topical adhesive property, enhanced skin retention and penetration in psoriasis-like lesions, and high intracellular uptake in epidermal cells compared with the counterparts. Subsequently, the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms, promoted the apoptosis of hyperproliferative epidermal cells, and alleviated the inflammatory cascade. The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation. Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.

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

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.

Objective:To investigate the value of monitor carotid velocity time integral (VTI) and corrected flow time (FTc) by bedside ultrasound before and after passive leg raising (PLR) in predicting fluid responsiveness in critically ill patients.Methods:A prospective observational study was conducted. Fifty patients with critical illness admitted to the First People's Hospital of Fuyang Hangzhou from January 2020 to March 2021 were enrolled. The clinical data including the gender, age, body mass index (BMI), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, and the duration of mechanical ventilation were recorded. The changes of carotid VTI and FTc were measured by bedside ultrasound, and the values of heart rate, mean arterial pressure (MAP), central venous pressure (CVP), stroke volume index (SVI), and intrathoracic blood volume index (ITBVI) were measured by pulse indicated continuous cardiac output (PiCCO) monitor before and after PLR in all patients. According to the changes of SVI before and after PLR, the patients were divided into fluid responsiveness positive group with the change rate of SVI≥15% and fluid responsiveness negative group with the change rate of SVI < 15%. The differences in the values of VTI, FTc, CVP, and ITBVI obtained before and after PLR (ΔVTI, ΔFTc, ΔCVP and ΔITBVI) were calculated and then compared between the two groups. The predictive values of these indicators on fluid responsiveness in critically ill patients were analyzed by receiver operator characteristic curve (ROC curve), and their relationship with the difference in SVI (ΔSVI) obtained before and after PLR was evaluated by Pearson correlation analysis.Results:Fifty patients were all enrolled in this study, in which 27 patients were fluid response and 23 patients were fluid nonresponse. Basic clinical data were not different between the two groups. The values of ΔVTI, ΔFTc, ΔCVP, and ΔITBVI in fluid response were all significantly higher than those in fluid nonresponse [ΔVTI (cm): 2.07±1.16 vs. 0.67±0.86, ΔFTc (ms): 4.00±6.10 vs. 0.01±2.26, ΔCVP (cmH 2O, 1 cmH 2O = 0.098 kPa): 1.67±1.14 vs. 1.00±1.17, ΔITBVI (mL/m 2): 98±69 vs. 48±70, all P < 0.05]. ROC curve analysis showed that ΔVTI, ΔFTc, ΔCVP and ΔITBVI were all positive for predicting fluid responsiveness, their area under ROC curve (AUC) and 95% confidence interval (95% CI) were 0.870 (0.769-0.972), 0.694 (0.547-0.841), 0.684 (0.535-0.832) and 0.709 (0.564-0.855), respectively. When using ΔVTI 0.92 cm, ΔFTc 1.45 ms, ΔCVP 1.50 cmH 2O and ΔITBVI 44.50 mL/m 2 as the threshold values, the sensitivities were 96.3%, 63.0%, 44.4% and 81.5%, and the specificities were 65.2%, 78.3%, 82.6% and 56.5%, respectively, in which the predictive value of ΔVTI was the largest. Pearson correlation analysis indicated that ΔVTI, ΔFTc, ΔCVP, and ΔITBVI were positively associated with ΔSVI ( r values were 0.971, 0.334, 0.440, 0.650, P values were 0.000, 0.018, 0.001, 0.000, respectively). Conclusion:Carotid ΔVTI and ΔFTc monitored by bedside ultrasound before and after PLR could be as effective as conventional indicators in predicting fluid responsiveness in critically ill patients, and the predictive value of ΔVTI was better than others.

Gastrointestinal nutrition tube is a special gastrointestinal tube designed for enteral nutrition, diagnosis, treatment and monitoring in severe patients. Clinically, it is inserted into patients' stomach for flushing, provide nutrition through stomach, duodenum or jejunum, and decompress gastrointestinal tract. It also can be used for gastric drainage, gastric juice pH value determination, and early diagnosis and treatment for stomach bleeding and other symptoms. Currently, gastrointestinal nutrition tube can only rely on guidewire and blind manipulation, or by gastroscopy, which may produce damage to the patients, including stimulating the digestive tract mucous membrane, and causing adverse reaction. Therefore, a new type gastrointestinal nutrition line was designed by the medical staff of intensive care unit (ICU) of the First People's Hospital of Fuyang District in Hangzhou according to the technical problems existing in the insertion of gastrointestinal nutrition tube, and National Utility Model Patent of China was obtained (ZL 2019 2 0118506.0). It included V-shaped joint, first pipe, second pipe, function module, supply pipe, scale line, upper clasp, lower clasp, elliptical balloon, elastic guide wire and infusion opening. Compared with the existed technology, it has multiple channels, functions and placement methods. The utility model has a simple structure and reasonable design, which can be very handy to insert and provide nutrient solution.

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 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 analyze the difference between indirect calorimetry (IC) and predicted energy estimation in patients with chronic obstructive pulmonary disease (COPD), and its possible factors affecting the difference, to provide reasonable energy supply basis for COPD patients. Methods A prospective cohort study was conducted. Twenty-six patients with COPD undergoing mechanical ventilation (MV) admitted to intensive care unit (ICU) of Hangzhou City Fuyang District First People's Hospital in Zhejiang Province from January to December in 2016 were enrolled. The energy values of patients were calculated by IC and predicted energy estimation, respectively. According to the degree of IC values deviating from the predicted energy estimation, the patients were divided into energy approaching group (IC values deviating from the empirical energy estimation ≤15%) and energy deviation group (IC values deviating from the empirical energy estimation > 15%). Bland-Altman diagram was drawn, and the consistency of the energy target values assessing by two methods was analyzed. The factors influencing the energy value deviation of the two measuring methods were screened by the multivariate Logistic regression and linear regression analysis. Results Twenty-six patients were enrolled in the final analysis. The energy target value of IC was significantly higher than that of predicted energy estimation (kJ: 7 079.3±1 213.4 vs. 6 527.0±949.8), and the difference between two values was statistically significant (P < 0.01). Bland-Altman heterogeneity analysis showed that the overall consistency of the energy values between the predicted energy estimation and IC was quite good. There were 14 patients in energy approaching group, and 12 in energy deviation group. There was no significant difference in gender, age, body mass index (BMI), type of COPD, or acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score between the two groups. In energy deviation group, the IC value of patients was significantly higher than predicted energy estimation (kJ: 7 711.1±1 125.5 vs. 6 556.3±907.9, P < 0.01). However, in energy approaching group, there was no significant difference between the energy values of IC and predicted energy estimation (kJ: 6 539.6±1 037.6 vs. 6 501.9±1 016.7, P > 0.05). Multivariate Logistic regression analysis showed that APACHEⅡ score was an independent risk factor inducing the deviation of energy evaluation between IC and predicted energy estimation [odds ratio (OR) = 1.403, 95% confidence interval (95%CI) =1.019-1.932, P = 0.038]. Multivariate linear regression analysis showed that the APACHEⅡ score increased by 1, and the energy deviation increased by 2.0 kJ (β = 0.476, 95%CI = 0.004-0.956, P = 0.047). Conclusions For patients with COPD, there was a good correlation between predicted energy estimation and the resting energy expenditure measured by IC. APACHE Ⅱ score was an independent risk factor inducing the deviation of energy evaluation between IC and predicted energy estimation. It is suggested that the target value of energy should be determined by IC for patients with high APACHE Ⅱ score.

OBJECTIVETo investigate the drug resistance, β-lactamase-encoding genes and protoporphyrin ferrochelatase-encoding genes of, and to explore its structure and pathogenic function.

METHODSThe strain was isolated by plate streaking method and identified by automatic bacteria detection system and 16S RNA gene PCR. Microdilution method was applied for drug susceptibility test. β-lactamases, extended spectrum β-lactamases (ESBL) and carbapenemases were detected using nitrocefin-disk, Kirby-Bauer disk, and Hodge test, respectively. Five β-lactamase-encoding genes and protoporphyrin ferrochelatase-encoding gene of the isolate were amplified by PCR for sequencing. Bioinformatic softwares were used to analyze the structure and function of the product of protoporphyrin ferrochelatase-encoding gene.

RESULTSA strain belonging towas isolated. This isolate was sensitive to cefepime, ciprofloxacin, ofloxacin and tigecycline, but resistant to five penicillins, four cephalosporins and two carbapenems antibiotics. The isolate produced β-lactamases but did not produce ESBL and carbapenemases. The isolate had five distinct β-lactamase-encoding genes and protoporphyrin ferrochelatase-encoding gene. The product of protoporphyrin ferrochelatase-encoding gene contained two functional domains of protoporphyrin ferrochelatase belonging to type Ⅱ chelatase superfamily that presented the most closely genetic relationship with the protoporphyrin ferrochelatase of.

CONCLUSIONSThe isolate ofhas a higher resistance to β-lactam antibiotics and its β-lactamase-encoding genes are different with the common bacterial β-lactamase-encoding genes. Protoporphyrin ferrochelatase may act as an important virulence factor of.

Objective To observe the clinical efficacy of treatment of diabetic nephropathy with Shuxuening injection combined with benazepril.Methods 60 cases from January 2014 to January 2015,were randomly divided into observation group and control group of 30 patients.the control group were given benazepril treatment,observation group were based on Shuxuening injection treatment,patients were followed up and record changes related indicators.Results The urinary β2-MG and hs-CRP were after treatment(0.38±0.08,6.29±1.40)mg/L,than the control group(0.48±0.10,7.74±1.36)mg/L,and the difference was significant sex(P<0.05); after treatment observation group 24H urine protein quantitative detection of(0.69±0.50)g/24h,than the control group(1.04±0.63)g/24h,and the difference was statistically significant(P<0.05); After the observation group patients,low-density lipoprotein,serum creatinine value were(359.2±50.3mg/L,2.40±0.63mmol/L,95.6±22.3mol/L),were better than the control group(379.8±48.3mg/L,3.44±0.76mmol/L,108.5±34.2mol/L),and the difference was statistically significant(P<0.05); observation group total effective rate was 90.0％,higher than 73.0 percent,and the difference was statistically significant(P<0.05).Conclusion Shuxuening injection combined with benazepril clinical treatment of diabetic nephropathy exact,no significant side effects,is worthy of further research and application.