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.

With the continuous advancement of China′s deepening medical reform, the reform of the primary healthcare service system has gradually become an important issue in health work. In recent years, Yuhuan city, Zhejiang province has taken the people-centered integrated care mode as the theoretical basis, focused on the construction of integrated outpatient clinics, and carried out extensive and in-depth integrated medical system reform with a series of measures such as policy guidance, financial support and medical insurance assistance. After the implementation of the integrated reform, patient satisfaction has continued to improve, the level of health management has steadily increased, and residents′ willingness to seek medical treatment locally has significantly increased. This can provide reference for the construction of an integrated medical service system at the grassroots level.

Hepatocellular carcinoma (HCC) has the features of high incidence rate, low survival rate, poor treatment outcome, and complex pathogenesis. In recent years, many studies have shown that long non-coding RNA (lncRNA) MALAT1 is upregulated in HCC and can promote the proliferation, invasion, and metastasis of HCC cells, and it can also guide the diagnosis, prognostic evaluation, and treatment of HCC in clinical practice. This article reviews the current status of research on lncRNA MALAT1 in HCC and discusses its expression pattern, mechanism of action, and clinical significance in predicting and monitoring the progression of HCC, so as to gain a deep understanding of the role of lncRNA MALAT1 in the progression of HCC. It is pointed out that lncRNA MALAT1 is expected to become a potential biomarker for the diagnosis and prognostic evaluation of HCC and may be used as a therapeutic target in clinical practice.

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.

Objective:To describe the COVID-19 epidemic and its characteristics in Heilongjiang province, and provide evidence for the further prevention and control of COVID-19 in the province.Methods:The information of COVID-19 cases and clusters were collected from national notifiable disease report system and management information system for reporting public health emergencies of China CDC. The Software’s of Excel 2010 and SPSS 23.0 were applied for data cleaning and statistical analysis on the population, time and area distributions of COVID-19 cases.Results:On January 22, 2020, the first confirmed case of COVID-19 was reported in Heilongjiang. By March 11, 2020, a total of 482 cases domestic case of COVID-19, The incidence rate was 1.28/100 000, the mortality rate was 2.70% (13/482) in 13 municipalities in Heilongjiang. There were 81 clusters of COVID-19, The number of confirmed cases accounted for 79.25% (382/482) of the total confirmed cases and 12 cases of deaths. The family clusters accounted for 86.42% (70/81). Compared with the sporadic cases, the mortality rate, proportion of elderly cases aged 60 or above and severe or critical cases of clinical classification were all higher in the clusters especially the family clusters, but the differences were not significant ( P>0.05). There were 34 clusters involving more than 5 confirmed cases accounted for 41.98% (34/81) of the total clusters, the involved cases accounted for 68.31% (261/382) of the total cases of clusters. There were significant differences in age distribution of the cases among the case clusters with different case numbers. In the clusters involving 6-9 cases, the proportion of cases aged 65 years or above was more (26.53%, 39/147). Conclusions:The incidence rate of COVID-19 was relatively high and the early epidemic was serious in Heilongjiang, The number of cases was large in clusters especially family clusters.

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.

Objective To investigate the situation about cognitive performance of critical care staffs in nutrition therapy for mechanical ventilated chronic obstructive pulmonary disease (COPD) patients in county hospitals.Methods A chart of questionnaire about nutrition therapy was formulated according to the current guidelines.Critical care staffs from 12 hospitals of county-level of Hang Zhou city were enrolled.The role of staffs in management of nutritional therapy for patients was observed to assess their cognitive performance and influence factors were analyzed according logistic analysis.Results A total of 137 staffs were enrolled.Almost all of the staffs thought that nutrition therapy for ventilated COPD patients was very important.About 90％ of the staffs never heard about the use of NRS2002 (nutritional risk screening 2002)to evaluation COPD patients but the rate of using it was higher among senior staffs (OR =1.08,95％ CI:1.01-1.16,P =0.04).Most of staffs assess the nutritional status of patients according to biomarkers and other methods.However,doctors might assess nutritional status more often according to their experience.The majority of staffs did choose enteral nutrition for patients especially seen in doctors and senior staffs (OR =3.10 and1.13,95％ CI:1.27-7.55 and 1.03-1.23,both P =0.01).For those without malnutrition,senior staffs did not choose parenteral nutrition (OR =0.14,95％ CI:0.04-0.57,P =0.01).Besides,senior staffs did not continue the enteral nutrition in patients with unstable haemodynamics (OR =1.10,95％ CI:1.03-1.16,P =0.002).Most of staffs considered that the head piece of bed was raised up to 30-45 degree and gastric residual volume monitoring was very important.However,compared with nurses,the cognitive performance of doctors was poorer (OR =0.39,95％ CI:0.18-0.83,P =0.01).Most of staffs thought that the nutrition therapy implementation checklist was necessary but it was used in only 20％ institutions.The understanding and demand for nutritional knowledge was more urgent among doctors than nurses (OR =3.13 and 5.33,95％ CI:1.45-6.75 and 1.13-25.02,P =0.004 and 0.03).Conclusions Nutrition therapy was important for ventilated COPD patients,but the staffs were not very familiar with nutritional knowledge.The cognitive performance of medical staffs was influenced by their profession and experience of practice.

The two-way referral system is an inevitable step in the health reform,as it could effectively channel patients,promote rational use of healthcare resources,and improve the quality of care at primary medical institutions.Only by means of resources integration for improvement of existing policies,and building a healthcare system comprising partnering medical institutions of all levels with proper division of responsibilities,can the two-way system come into practice smoothly.This will alleviate the difficulty in seeing doctors and expensiveness of treatment.

Objective To detect the relationship between plasma B-type natriuretic peptide(BNP) and left ventricular function in elderly patients with maintenance hemodialysis (MHD). Method Plasma BNP concentration were measured in 50 MHD patients (MHD group) and 30 healthy controls (control group). Echocardiographic examinations were performed including left ventricular ejection fraction (LVEF). Results The median plasma BNP level in MHD group before and after hemodialysis was 213.5 ng/L and 110.2 ng/L, and obviously higher than that in control group (20.2 ng/L) (P<0.01). Spearman rank correlation showed that plasma BNP level was significantly negatively correlated with LVEF (r=-0.4357, P< 0.05). The median plasma BNP level in the patients with LVEF < 50% before and after hemodialysis was 386.5 ng/L and 232.0 ng/L, significantly higher than that in the patients without left ventricular dysfunction (LVEF≥50%) (59.7 ng/L and 29.1 ng/L)(P<0.01). Conclusions The level of BNP may reflect dynamic change of left ventricular function in MHD patients. It can help to diagnose and treat cardiovascular disease in MHD patients early.