Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective:To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018.Methods:All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis.Results:871 (40.1 %) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1 %) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7 %) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions:HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.

[Summary] The aim of the study was to explore the effect and its clinical relevance of short -term intensive insulin treatment on plasma concentrations of lipoprotein-associated phospholipase A 2 ( Lp-PLA2 ) and secretory phospholipase A2(sPLA2) in newly diagnosed type 2 diabetes mellitus (T2DM).Ninety newly diagnosed T2DM patients were recruited and received continuous subcutaneous insulin infusion (CSII) for about 2 weeks.After CSII, sPLA2 levels [173.78 (80.95, 278.09) μg/L] were significantly decreased compared with the levels before [219.33 (130.03, 337.30) μg/L], P <0.01, while no statistic significant changes could be viewed in Lp-PLA2 levels.Correlation analysis showed that the changes of Lp-PLA2 and sPLA2 were both positively correlated with the changes of homeostasis model assessment of insulin resistance(HOMA-IR)after CSII (r=0.537,0.493 respectively, all P<0.05).The Lp-PLA2 and sPLA2 level reduction after CSII might help to protect the patients from diabetic macroangiopathy . Trial registration Chinese Clinical Trial Registry , ChiCTR-TRC-10001618.

Objective To investigate the features of lipid ratios in patients with newly diagnosed T2DM, and the effects of intensive insulin treatment on them. Methods 90 patients with newly diagnosed T2DM and 58 matched people with normal glucose were enrolled to assess height,weight,waist circumference,blood glucose and lipid profiles. BMI,TC/HDL-C,TG/HDL-C,log(TG/HDL-C),LDL-C/HDL-C,HOMA-B and HOMA-IR were calculated respectively. All the patients received the continuous subcutaneous insulin infusion with insulin pump. The treatment continued for more 10~14 days after blood glucose reached the standard. All the above indi-cators were reexamined after treatment. Results Dyslipidemia in patients with newly diagnosed T2DM mainly showed as hypertriglyceridemia and decreased HDL-C compared to the control group(P<0.05). TC/HDL-C,TG/HDL-C,log(TG/HDL-C)and LDL-C/HDL-C significantly increased in these patients(P<0.01). After short-term intensive insulin therapy,all lipid ratios were significantly decreased and the changes of lipid ratios were positively correlated with the change of HOMA-IR(P<0.05). Conclusion Short-term intensive insulin therapy for patients with newly diagnosed type 2 diabetes can significantly lower the lipid ratios related to HDL-C. The effects may be closely related to improvement of insulin resistance.

_ Objective_ To evaluate plasma concentrations of lipoprotein-associated phospholipase A2 (LP-PLA2)andsecretoryphospholipaseA2(sPLA2)inpatientswithnewlydiagnosedtype2diabetes,andtoexplore their clinical significance. Methods Oral glucose tolerance test ( OGTT) was carried out in our hospital to all the subjects without history of diabetes. According to the results of OGTT, they were divided into two groups:patients with newly diagnosed type 2 diabetes and subjects with normal fasting glucose and normal glucose tolerance. Anthropometric data such as height, weight, waist circumference, and blood pressure were measured and concentrations of blood glucose, insulin, lipid profile ( including total cholesterol, triglycerides, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol), LP-PLA2, and sPLA2 were determined in both groups. Results Ninety patients with newly diagnosed type 2 diabetes and fifty-eight subjects with normal glucose tolerance were enrolled in our study. As to gender, age, body mass index, blood pressure, and lipid profile, there were no statistically differences between these two groups (P>0. 05). Plasma levels of LP-PLA2 and sPLA2 in diabetic patients were significantly higher than normoglycemic participants [102. 98(76. 34,134. 31) vs 50. 89(23. 71,90. 40) ng/ml, 219. 33 (130. 03,337. 330) vs 78. 55 (75. 15,87. 02) ng/ml, both P<0. 01]. Plasma concentrations of LP-PLA2 and sPLA2 in diabetic patients with atherosclerosis were significantly higher than those without [ 133. 43 ( 111. 54, 145. 17 ) vs 99. 11 ( 63. 02, 130. 85) ng/ml,235. 73 (180. 48, 416. 46) vs 182. 97 (9. 08, 280. 79) ng/ml, both P<0. 05]. LP-PLA2 and sPLA2 were both positively correlated with homeostasis model assessment for insulin resistance (HOMA-IR), while negatively correlated with insulin function index. In a multiple linear regression analysis, LP-PLA2 and sPLA2 were independent correlative factors of HOMA-IR(both P<0. 05). Conclusions Plasma levels of LP-PLA2 and sPLA2 were significantly higher in patients with newly diagnosed type 2 diabetes than in individuals with normal glucose tolerance, even more significant in diabetic patients with atherosclerosis. And their concentrations were both closely related to insulin resistance.

Aedes ; virology ; Animals ; China ; epidemiology ; Genetic Variation ; Genome, Viral ; Humans ; Multigene Family ; Viral Proteins ; genetics ; Zika Virus ; classification ; genetics ; isolation & purification ; Zika Virus Infection ; epidemiology ; virology

Objective To compare the incidence of metabolic disorders and uric acid (UA) levels between patients with primary aldosteronism (PA) and essential hypertension (EH),and to explore factors associated with UA levels in these patients.Methods A total of 117 PA and 117 EH patients individually matched by sex,age,blood pressure and duration of hypertension were recruited from in-hospital patients who were hospitalized in our department because of suspicion of secondary hypertension from January 2008 to December 2014.Clinical data including metabolic disorders and UA levels were analyzed.Results (1) Body mass index (BMI),waist circumference,plasma triglyceride (TG),low-density lipoprotein cholesterol (LDL-C),free fatty acid (FFA) were significantly higher in EH than in PA group (all P ＜ 0.05).Prevalence of diabetes mellitus or impaired glucose tolerance (DM + IGT) was significantly higher in EH than in PA group (41.9％ (49/117) vs.17.1％ (20/117),P ＜0.01).The prevalence of metabolic syndrome (MS) was also significantly higher in EH than in PA group (51.3 ％ (60/117) vs.24.8％ (29/117),P ＜ 0.01).(2) EH patients had higher homeostasis model assessment for insulin resistance (HOMA-IR) and lower insulin sensitivity index composite (ISI comp) than PA patients,but basic insulin secretion index (HOMA-β) and modified β cell function index (MBCI) were significantly lower in PA than in EH group (P ＜ 0.05).(3) With regard to target organs damages,PA patients revealed higher 24-hour urinary protein,urinary albumin excretion rate (UAER),urinary IgG,urinary α-1 microglobulin,left ventricular mass index and lower urine specific gravity than EH patients (all P ＜ 0.05).There was no significant difference in estimated glomerular filtration rate (eGFR) between two groups (P =0.103).(4) UA level was significantly lower in PA group than in EH group ((314.00 ±89.52) μmol/L vs.(379.16 ± 101.25) μmol/L,P ＜ 0.01).Higher plasma aldosterone concentration and lower plasma renin activity were associated with lower UA level in PA group.Conclusions Compared with sex,age and hypertension duration matched EH patients,PA patients revealed lower UA level and less severe abnormalities of glucose and lipid metabolism,but are associated with severer renal and cardiac damages.The reduced UA level in PA patients is possibly due to the high plasma aldosterone concentration and low plasma renin activity.

OBJECTIVETo investigate the relationship between cytogenetic markers with World Health Organization (WHO) classification, disease progress and prognosis in cases with primary myelodysplastic syndromes (MDS).

METHODS298 patients with de novo MDS from the first affiliated hospital of medical school, Zhejiang University were enrolled in the retrospective analysis of WHO classification, karyotype, and prognosis. Follow-up study was also conducted.

RESULTSThe WHO classifications at first diagnosis were as follows: refractory cytopenia with unilineage dysplasia (RCUD), 18 cases; refractory anemia with ring sideroblasts (RARS), 8 cases; refractory cytopenia with multiline dysplasia (RCMD), 104 cases; refractory anemia with excess blasts-1, 76 cases; refractory anemia with excess blasts-2, 85 cases; MDS unclassified (MDS-U), 5 cases involved; and single del (5q), 2 cases. 39.6% of MDS patients carried karyotypic abnormalities. Among them, the frequency of numerical abnormalities, structural abnormalities and the existence of composite abnormalities were 45, 31, and 42, respectively. The composite abnormalities were unbalanced translocations and complex chromosomal abnormalities. The incidence of both karyotypic abnormalities and complex chromosomal abnormalities in RAEB group was higher than that in non-RAEB group (P<0. 05). An analysis based on IPSS-R Scoring System showed that advanced risk stratification (except the low-risk group) gradually enhanced the incidence of karyotypic abnormalities (P<0.05). In addition, the probability of evolution to leukemia increased with the higher IPSS-R score (P<0.05). In RAEB group, the cases with +8 chromosome, accounting for 19.5% of karyotypic abnormalities, had worse prognosis than those with normal chromosomes.

CONCLUSIONKaryotype was identified with an independent risk factor in MDS patients. Therefore, the information on cytogenetic analysis was critical for diagnosis, prognosis and individual treatment. MDS patients presenting+8 chromosome, an intermediate risk factor, were associated with a poorer outcome compared to cases with normal chromosomes in RAEB group.

Abnormal Karyotype ; Anemia, Refractory ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; Follow-Up Studies ; Humans ; Karyotyping ; Myelodysplastic Syndromes ; Prognosis ; Retrospective Studies ; Risk Factors ; World Health Organization

Objective:The goal of this study was to analyze the clinical significance of relationship between myocardial collateral and the levels of hypoxia‐inducible factor 1‐alpha (HIF‐1α) and vascular endothelial growth factor A (VEGF‐A) in patients with coronary chronic total occlusion lesion .Methods:89 patients with coronary chronic total occlusion lesion confirmed by clin‐ical data and coronary angiography were identified .The levels of HIF‐1αand VEGF‐A were measured by ELISA ,and the rela‐tive expression of VEGF‐A of peripheral blood mononuclear cell (PBMC) were measured by real‐time PCR .The results were statistically analyzed by the statistical programme for social sciences (SPSS version 18 .0) and software SAS JMP 9 .0 .Results:Compared to Rentrop 0‐1 grade group (18/38 ,47 .4% ) ,Rentrop 2 (11/31 ,35 .5% ) and Rentrop 3 (3/20 ,15 .0% ) grade group had fewer diabetes mellitus .Rentrop 2 [(6 .67 ± 1 .41) mmol/L] and Rentrop 3 [(5 .48 ± 1 .26) mmol/L] grade group had low‐er fasting blood glucose than Rentrop 0‐1 grade group [(7 .24 ± 1 .39) mmol/L] .Rentrop 2 (12/31 ,38 .7% ) and Rentrop 3 (3/20 ,15 .0% ) grade group had fewer clinical heart failure (NYHA Ⅱ ~ Ⅳ grade) than Rentrop 0‐1 grade group (20/38 , 52 .6% ) .Rentrop 2 [(85 .5 ± 27 .7) pg/mL ,(139 .5 ± 42 .1) pg/mL] and Rentrop 3 [(103 .3 ± 30 .2) pg/mL ,(162 .6 ± 43 .3) pg/mL] grade group had higher levels of HIF‐1αand VEGF‐A than Rentrop 0‐1 grade group [(42 .0 ± 16 .1) pg/mL ,(76 .5 ± 32 .2) pg/mL] .Rentrop 2 (1 .31 ± 0 .46) and Rentrop 3 (1 .38 ± 0 .44) grade group had higher level of relative expression of VEGF‐A in PBMC than Rentrop 0‐1 grade group (1 .00 ± 0 .28) .Conclusions:Chronic and consistent ischemia and hypoxia in‐duced the increase of expression of HIF‐1αand VEGF‐A is important for establishment of coronary collateral ,increasing blood supply and improving the heart function and prognosis .