Objective To study the value of magnetic resonance vessel wall imaging in assessing the atherosclerotic plaque burden of rabbit model.Methods We built up abdominal atherosclerotic animal model in 30 New Zealand rabbits by high lipid diet combined with abdominal artery denudation.The animals were divided into 3 groups randomly,which were the 1-week group,1-month group and 2-months group.The MRI and histology examination were carried out at relative time points.The correlations of area or thickness of vessel wall by MRI with histology examination were analyzed.Results Among the 30 rabbits,3 died due to anesthesia or surgery,one rabbit model failed because of the thin vessel,and another 3 died of diarrhea or inflammation during the high lipid diet feeding.Eventually,totally 23 rabbits fulfilled the examinations (7 in 1-week group,7 in 1-month group and 9 in 2-months group).The vessel wall area of histology examination grew larger along with the post-surgery duration,from 1.7663 mm2of 1-week group to 2.4371 mm2 of the 1-month group till 3.5978 mm2 of 2-months group,with statistic significant difference among 3 groups (F=5.052,P=0.017).There were strong correlations of area or thickness vessel wall resulted from MRI with histology examination(r=0.688,0.642;P=0.001,0.002).Conclusions High resolution MR vessel wall imaging technique may evaluate and follow up the plaque burden in the early stage of atherosclerosis.

Objective: To compare the distribution characteristics of left ventricular configuration in Chinese adult patients with hypertension under Chinese and international standard using echocardiography. Methods: A total of 201 patients with primary hypertension were included in the study.Left ventricular end systolic left atrial diameter (LAD), ascending aortic diameter (AO), left ventricular end diastolic diameter (LVDd), left ventricular posterior wall thickness (PWTd) and ventricular septal thickness (IVSd) were measured and then relative wall thickness (RWT), left ventricular mass (LVM), left ventricular mass index (LVMI) were calculated. Left ventricular systolic left atrial volume (LAV) was measured by Simpson′s biplane method and left atrial volume index (LAVI) was then calculated. Ganau classification was done according to Chinese and international standard respectively. The differences of left ventricular configuration in hypertension were compared. Results: According to the Chinese standard, the analytic results of left ventricular configuration showed that there were 103 cases (51.2%) in normal configuration (NG) group, 28 cases (13.9%) in concentric remodeling (CR) group, 52 cases (25.9%) in eccentric hypertrophy (EH) group and 18 patients (9.0%) in hypertrophic (CH) group, respectively. Whereas, according to the international standard, there were 47 cases (23.4%) in NG group, 93 cases (46.3%) in CR group, 18 cases (8.9%) in EH group and 43 cases (21.4%) in CH group.Each group in the configuration analysis had significant difference between Chinese and international standard (P<0.01). Patients with left atrial enlargement according to the Chinese and international standard had statistical difference in the EH and CH groups (P<0.05). Conclusions Analysis of left ventricular configuration according to the Chinese and international standard has significant difference. According to Chinese standard, it may be more accurate to reflect the changes of left ventricular configuration in Chinese hypertensive population, so as to evaluate the changes of left heart structure and function more accurately.

OBJECTIVE:To provide reference for guarantee the supply of short-landed drugs.METHODS:A questionnaire survey was conducted to investigate the drug shortage in 40 medical institutions in China.Based on the survey data,the econometric model was built to analyze the reasons for drug shortage in medical institutions.RESULTS:40 questionnaires were issued and 26 valid questionnaires were collected with effective recovery rate of 65.0％.The institutions surveyed received 87 samples of short-landed drugs,involving 33 drugs;82.8％ of short-landed drug samples were in short supply for more than 3 months,and even 21.8％ short-landed drug samples were in short supply for more than 12 months.The common reasons for drug shortage mainly included:not entering the provincial bidding directory;adopting the government pricing method;being redistribution system;not establishing provincial normal reserve mechanism.In addition to common reasons,there were some personality reasons for drug shortage based on the necessity of clinical needs,drug attributes and drug price.CONCLUSIONS:There are many reasons for the shortage of drugs in medical institutions.There are both common causes and personality reasons.It is necessary to solve many problems of drug shortage from the source,and it needs many policies and systems to cooperate with them.

Objective:To observe the efficacy of anti-sensitive moisturizing tolerance-extreme cream combined with isotretinoin in the treatment of severe acne.Methods:Fifty patients with severe acne were selected in the Dermatology Clinic of the Third People＇s Hospital of Hangzhou from November 2018 to July 2019. They were randomly divided into the experimental group of 25 cases and the control group of 25 cases. The experimental group was treated with anti-sensitive moisturizing tolerance-extreme cream combined with isotretinoin orally. The control group was treated with isotretinoin orally alone. Before and after treatment for 56 days, lactate score, skin cuticle hydration (SCH), transepidermal water loss (TEWL) and skin physiological indexes were measured.Results:After 56 days of treatment, the TEWL and SCH of the control group were 15.75±3.31 and 10.13±3.62, the TEWL and SCH of the experimental group were 12.17±3.61 and 28.07±3.17, respectively; the difference was statistically significant ( T was 3.610 and 12.398, P was 0.002 and 0.000, respectively). The volume and depth of cyst nodule, scar depression, skin roughness, absolute value and area of erythema in the experimental group were significantly lower than those in the control group ( T was 2.280, 1.676, 2.332, 1.508, 4.813 and 3.637; P was 0.031, 0.011, 0.027, 0.040, 0.000 and 0.001, respectively). Conclusions:Anti-sensitive moisturizing tolerance-extreme cream combined with isotretinoin has a good effect on severe acne and it can reduce the barrier damage and other adverse reactions.

Objective:To investigate the effect of human tumor suppressor folliculin (FLCN) on the expression of melanocyte chemokines (MC) mediated by immune factors in vitiligo.Methods:The MC of vitiligo patients that received autologous melanocyte transplantation in the Department of Dermatology, Hangzhou Third People′s Hospital from January to April 2019 were collected. The blister fluid of the white spot and the normal part was taken. Western blot was used to analyze the expression difference of MC and FLCN protein in normal, vitiligo patients and that induced by immune factors; FLCN shRNA lentivirus was constructed by shRNA and transfected into normal MC (FLCN shRNA MC) to interfere with the expression of silenced FLCN gene. The effect of immune factors on chemokines in FLCN shRNA MC was detected by ELISA.Results:The results of Western blot showed that FLCN protein was highly expressed in melanocytes of vitiligo patients, immune factors stimulated FLCN protein expression in normal melanocytes significantly increased ( t=1.27; P<0.001), chemokine CXCL10 and CCL20 also significantly increased ( t=104.53 and 60.21, respectively; P<0.001). The expression of FLCN in FLCN shRNA MC was significantly decreased ( F=1.95, P<0.001); and the high expression of CXCL10 and CCL20 induced by immune factors was significantly inhibited ( F=93.676 and 74.096, all P<0.001). Conclusions:Immune factors can stimulate the expression of CXCL10 and CCL20, which are closely related to vitiligo, while FLCN is a key protein involved in immune factors inducing melanocyte chemokine expression.

Objective:To investigate the role of folliculin in apoptosis of and chemokine secretion by melanocytes mediated by interferon-γ (IFN-γ) .Methods:Normal primary melanocytes were isolated from circumcised foreskin tissues from a healthy male child, and primary vitiliginous melanocytes were isolated from normally pigmented suction-blistered epidermis from patients with vitiligo after suction blister epidermal grafting. Western blot analysis was performed to determine the folliculin protein expression in normal primary melanocytes, primary vitiliginous melanocytes and a human primary melanocyte line PIG1. PIG1 cells stimulated with 10 ng/ml IFN-γ for 48 hours served as induction group, and untreated PIG1 cells served as control group. Real-time quantitative RCR (qRT-PCR) was performed to determine the mRNA expression of folliculin, autophagy-related microtubule-associated protein 1 light chain 3 (LC3) -Ⅱ and Beclin genes, and Western blot analysis to determine the protein expression of folliculin, Beclin1 and LC3Ⅱ/Ⅰ, as well as phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in the above cells. Furthermore, the melanocytes stimulated with 10 ng/ml IFN-γ for 48 hours were divided into several groups: negative control group infected with an empty lentiviral vector, folliculin inhibition group infected with a folliculin-inhibiting lentivirus, autophagy enhancement group infected with a folliculin-inhibiting lentivirus followed by 2-hour treatment with a mTOR inhibitor, autophagy inhibition group infected with a folliculin-inhibiting lentivirus followed by 2-hour treatment with an AMPK inhibitor. Then, flow cytometry was conducted to detect apoptosis of PIG1 cells, and enzyme-linked immunosorbent assay to measure the concentration of chemokines CXCL10 and CCL20 in the culture supernatant of PIG1 cells in the above groups. Measurement data were compared among multiple groups by using one-way analysis of variance, and multiple comparisons were carried out by using least significant difference- t test. Results:The relative protein expression level of folliculin significantly differed among the normal primary melanocytes (0.850 ± 0.120) , primary vitiliginous melanocytes (1.507 ± 0.170) and PIG1 cells (0.697 ± 0.130; F = 50.09, P < 0.001) , and was significantly higher in the primary vitiliginous melanocytes than in the normal primary melanocytes and PIG1 cells ( t = 4.06, 5.89, respectively, both P < 0.01) . Compared with the control group, the induction group showed significantly increased relative mRNA and protein expression levels of folliculin (both P < 0.01) , but significantly decreased relative mRNA and protein expression levels of LC3Ⅱ and Beclin (all P < 0.01) ; moreover, the induction group showed significantly decreased LC3Ⅱ/Ⅰ levels (0.72 ± 0.02) and AMPK phosphorylation levels (0.714 ± 0.023) in the PIG1 cells compared with the control group (1.13 ± 0.02, 1.176 ± 0.002, t = 7.34, 6.67, respectively, both P < 0.01) , but significantly increased mTOR phosphorylation levels (1.051 ± 0.023) compared with the control Group (0.451 ± 0.016, t = 3.81, P = 0.009) . There were significant differences in the PIG1 cell apoptosis rate and concentrations of CXCL10 and CCL20 among the control group, induction group and other treatment groups (all P < 0.001) ; specifically, the PIG1 cell apoptosis rate and concentrations of CXCL10 and CCL20 were significantly higher in the induction group than in the control group, lower in the folliculin inhibition group than in the negative control group, lower in the autophagy enhancement group than in the folliculin inhibition group, and higher in the autophagy inhibition group than in the folliculin inhibition group (all P < 0.05) . Conclusions:Folliculin is highly expressed in vitiliginous melanocytes. Folliculin expression and downstream signaling pathways are regulated by IFN-γ, and folliculin may participate in IFN-γ-mediated melanocyte apoptosis and chemokine secretion via regulating autophagy.

BACKGROUND: The clinical trials of new anti-tumor drugs are prospering in China. The acceptance of clinical trials in patients is an important factor affecting the speed and quality of clinical trials. Previous studies have investigated the acceptance of clinical trials in those cancer patients, who have never participated in a trial. This study is designed to investigate and compare the acceptance and related causes of clinical trials in cancer patients who have once participated in a clinical trial or not. METHODS: From June 2018 to April 2019, a standardized questionnaire-based survey was conducted among two groups of cancer patients classified by history of clinical trial participation in Cancer hospital, Chinese Academy of Medical Science, mainly focusing on their overall acceptance of clinical trials and related considerations, including the role of attending doctors, as well as group differences between the two participants. RESULTS: A total of 538 patients were enrolled with an average age of 53.5 years old, 51.1% of whom were males, and 43.3% of whom have never participated in a clinical trial. Overall, 502 patients (93.3%) were willing to or recommend their relatives or friends to participate in clinical trials, and patients with history of clinical trial participation had higher willingness (96.6% vs 90.8%, P=0.008). Patients were most likely to be motivated by expectation of optimal treatment (100.0% vs 99.3%) for both those who had once participated in a clinical trial or those not, respectively followed by financial burden reduction (56.0%) and recommendation by attending doctor (43.7%). The main reasons for unwillingness-to-participate for those who had once participated in a clinical trial were abandoning other treatment options, divided into control group or additional visits, while for those who had never participated in a clinical trial, ineffective treatment or serious adverse reactions were their main concerns. In the decision-making of clinical trial participation, 88% patients highly valued the role of recommendation by attending doctors. Among patients without trial participation history, 60.9% of those had no unwillingness-to-participate expressed that recommendation by attending doctors would change their decisions. The study also reported patients' preferences for information and access to clinical trials. CONCLUSIONS The acceptance of clinical trials in cancer patients in our hospital is generally high, especially in patients who had a history of trial participation. It's of substantial significance to give full play to the role of doctors in improving the acceptance of clinical trials of cancer patients in China.