Objective To determine LDLR gene mutation in 2 clinically diagnosed FH patients from Hubei province and provide basis for gene diagnosis of FH.Methods Clinical data of 2 FH patients and their parents were collected.The promoter region and exon 1 to exon 18 region of LDLR gene were amplified through PCR and the amplified products were analyzed by forward and reverse DNA sequencing.The mutations were identified after comparison with LDLR gene sequence in GenBank.The pathogenic gene mutations were confirmed according to both genotype and phenotype of FH probands.Results The levels of plasma TC of two probands were 12.79 and 11.98 mmol/L.respectively.No gene mutations were detected in region 3 500 to 3 531 of ApoB100. The mutations of LDLR gene were compound heterozygous mutations. The novel mutation 665G > T detected in the exon 4 of No. 1 proband's LDLR gene was heterozygous missense mutation. The novel mutation 1 358 +32C > T was detected in the exon 9 of No. 1 proband's LDLR gene.The mutations 665G > T ( paternal origin) and 1 358 + 32C > T ( maternal origin) were inherited from the parents. A novel mutation 1 257 C > A was detected in the exon 9 of No. 2 proband's LDLR gene, resulting the presence of a premature termination codon, which was different from 1 257 C > G reported in Belgium.Another heterozygous missense mutation 1 879 G > A was detected in exon 13. They were derived from paternal origin and maternal origin, respectively. Conclusions There are three novel gene mutations:665G >T, 1 358 +32C > T, 1 257C > A found in two probands with compound heterozygous mutations in LDLR respectively. They maybe play a potential role in FH pathogensis.

Objective To explore the efficiency of prophylactic intravesical chemotherapy after nephroureterectomy for primary upper tract urothelial carcinoma.Methods Forty-seven patients with primary upper tract urothelial carcinoma who underwent nephroureterectomy were retrospectively analyzed.There were 25 male and 22 female patients with mean age of 68 years.Patients were divided into intravesical chemotherapy group (n =32) and non-intravesical chemotherapy group (n =15).In the intravesical chemotherapy group, there were 14 male and 18 female patients with mean age of 70.3 years;20 cases located at left side while 12 at the right side.In non-intravesical chemotherapy group, There were 11 male and 4 female patients with mean age of 65.0 years;10 cases located at left side while 5 at the right side.The age, gender, side of the two groups were not statistical different.The two groups were followed up, and the tumor stage, grade, recurrence rate, cancer-free survival time were compared.Results The pathology results of all cases were urothelial carcinoma.In the intravesical chemotherapy group, 23 cases were high grade tumors with 9 low grade tumors.There were 15 cases of Ta-T1 stage, 8 cases of T2 stage and 9 cases of T3 stage;the tumor of 19 cases located at pelvis, 12 located at ureter, 1 located at pelvis and ureter;the mean size of the tumors was (2.75 ± 1.49) cm;8 cases were multiple while 24 were single.In the non-intravesical chemotherapy group, 12 cases were high grade tumors with 3 low grade tumors, there were 6 cases of Ta-T1 stage, 4 cases of T2 stage and 5 cases of T3 stage;the tumor of 11 cases located at pelvis, 3 located at ureter, 1 located at pelvis and ureter;the mean size of the tumors was (3.11 ± 1.48) cm;6 cases were multiple while 9 were single.The items mentioned above did not reach statistical difference between the two groups(P ＞0.05).6 patients relapsed in intravesical chemotherapy group while 7 in non-intravesical chemotherapy group.The recurrence rate of bladder cancer of intravesical chemotherapy group was lower than that of non-intravesical chemotherapy group (18.75％ vs.46.67％, χ2 =3.978, P =0.046).Compared with non-intravesical chemotherapy group, intravesical chemotherapy group had longer cancer-free survival, but it did not reach statistical difference (36.5months vs.29.6months, t =1.079, P =0.286).The age and tumor grade were risk factors of bladder cancer recurrence, meanwhile the gender, tumor side, tumor stage, voided urine cytology, tumor size, and location were not.Conclusion Prophylactic intravesical chemotherapy after nephroureterectomy for primary upper tract urothelial carcinoma could reduce the recurrence rate of bladder cancer.

Objective: To explore the associations of Hand-Foot-Mouth disease (HFM) among children of different age groups in kindergartens, and to provide scientific evidence for HFM prevention and control. Methods: Cluster sampling was used to select 9 912 children from 40 kindergartens. The major caregivers of children were invited to participate into the study and fulfill a self-administered questionnaire that consisted of general background, hand washing and the history of HFM among children in the recent 1 year. Chi-square and binary logistic regression were applied,to analyze the influencing factors of HFM among children of different age groups. Results: In the 2 year-old-group, children who were male (OR=1.76, 95%CI=1.24-2.50), had the major caregiver with high school educational background or below (OR=1.54, 95%CI=1.06-2.24), had family income more than 100 000 yuan or more per year(OR=1.49, 95%CI=1.01-2.20), children whose major caregiver seldom wash hands immediately after coming home(OR=2.10, 95%CI=1.05-4.19)，and 3-5 times per week(OR=2.07, 95%CI=1.26-3.41) were more likely to have HFM. In the 3 year-old-group, the more time children spent in the outdoors, the less likely they got HFM(3-5 times per week: OR=0.58, 95%CI=0.43-0.81; ≥6 times per week: OR=0.45, 95%CI=0.29-0.70). Children whose major caregiver did not use soap were more likely to have HFM(OR=1.67, 95%CI=1.11-2.49). In the 4 year-old-group, children who occasionally took toys when going out were less likely to get HFM (vs always, OR=0.57, 95%CI=0.38-0.88). No significant factors were found in the 5 year-old-group. Conclusion The behaviors and activities of major caregivers and children could influence the HFM incidence.To prevent HFM, it was advised that the major caregivers should wash hands immediately after coming home, and develop the habit of using soap for handwashing together with children at the earlier age, and encourage children to take more outside-door activities according to the age characteristics. Attention should be paid to avoid contaminating takeout snacks, and to clean the takeout toys timely.

Objective: To analyze the features of Norovirus outbreaks in schools and kindergartens and the associated factors in Chengdu, 2017, and to provide the scientific basis for Norovious outbreaks prevention and control. Methods: A total of 75 schools and kindergartens in Chengdu of 2017 participated in the study about Norovirus outbreaks. ANOVA and binary Logistic regression models were used to analyze the influencing factors and duration of Norovirus outbreaks. Results: Overall 710 cases were included. There was an average of 9.47 cases and 27.52 hours for each outbreak,decreasing by 1.06 cases and 10.56 hours compared with those of 2016. Most outbreaks happened in kindergartens and in the firstlevel economy regions from January to March, with GII type as the main outbreak. Compared with the first case of vomiting at home, vomiting in public area (OR=11.76, 95%CI=1.63-84.69) was much more serious, and compared with the active report of school/ community, being informed of the outbreak passively (OR=4.09，95%CI=1.04-16.03) was positively associated with outbreak severity. Conclusion To prevent Norovirus infection, specific development and training of dealing with vomiting and feces should be introduced, and measures to increase the ability to surveil and report Norovirus outbreaks should be enhanced.

Objective:This paper aim to analyze the influencing factors of individual academic performance based on the construction of a research-oriented hospital, to provide possible reference for improving the service of science and technology management.Methods:Selecting 45 experts determine the constituent index and assign value of the academic performance evaluation system by using Delphi method. The index setting emphasized clinical application orientation, and weighted total score was used as the academic performance evaluation standard. Conduct a-350-person anonymous questionnaire survey and use descriptive analysis and multiple logistic regression methods to analyze the influencing factors.Results:The system includes a total number of 6 first-level indicators and 43 second-level indicators. The authoritative coefficients of the consulting experts are 8.5±0.6, and the Kendall of the two rounds of consultation are 0.78 and 0.83( P<0.05). The questionnaire results show that respondents with Ph. D degree, senior professional titles, mentor qualification, from large team and higher scientific research service support have better academic performance. personal background, team support and scientific research services have significant impact on academic performance. Conclusions:In order to improve the scientific research strength of the hospital, it is significant to focus on systematic scientific research training, strengthening discipline teams and research platforms, and improving the professional level of scientific research management.

Objective To study the clinical and pathologic factors for prognosis of children and adolescents with thyroid carcinoma.Methods Clinicopathological data of 110 children and adolescents with thyroid carcinoma at the Affiliated Tumor Hospital of Zhengzhou University from January 1984 to March 2008 were collected and reviewed in this study.Univariate analysis was performed by using Log－rank test to determine predictors of survival,and multiva-riable analysis was performed by a Cox regression model.Results The overall 5－ year and 10 －year survival rates were 95.5%,88.2%,respectively.Gender and histopathologic typing were not related to prognosis.The 5 －year and 10－year survival rates in group ≤12 years old were 91.7% and 81.3%,and those in group ＞12 years old were 98. 4% and 93.5%,respectively.The 5－year and 10－year survival rates in stage T1 and T2 were 100.0%,in stage T3 were 100.0% and 66.7%,respectively,and those in stage T4 were 58.3% and 0.The 5－year and 10－year sur-vival rates in N0 group and N1a group were 100.0%,and those in N1b group were 93.4% and 82.9%,respectively. For patients without the distant metastasis group,the 5－year and and 10－year survival rates were all 96.9%,which were significantly higher than those in the distant metastasis group(84.6%,23.1%).The 5－year and 10－year sur-vival rates in groupⅠwere all 97.8%,those in groupⅡwere 84.6% and 23.1%,respectively,and those in groupⅣwere all 75. 0%.The 5－year and 10－year survival rates in the solitary lesions group were 98.7%,in the multiple le-sions group were 88.2% and 64.7%,respectively.For differentiated thyroid carcinoma,the 5－year and 10－year sur-vival rates in low,and medium risk groups were all 100.0%and those in high risk group were 83.3% and 50.0%,re-spectively.There was a significant relationship between survival and age group,T stage,N stage,M stage,TNM stage, the number of lesions,and risk stratification(all P＜0.05).The Cox regression analysis showed that T stage and M stage were the independent prognostic factors.Conclusions The primary tumor and distant metastatic are important factors affecting the prognosis of children and adolescents.Earlier diagnosis for primary tumor and aggressive manage-ments for metastatic lesions are critical to the survival rate of children and adolescents with thyroid carcinoma.

Objective:To investigate the clinical characteristics, prognosis, and risk factors for poor prognosis of neuropsychiatric systemic lupus erythematosus (NPSLE) .Methods:Patients who were diagnosed as NPSLE between January 2009 to January 2019 in Peking University First Hospital were included. Patients with neuro-psychiatric symptoms caused by other reasons such as infection and metabolic disorders were excluded. Patients were retrospectively followed up by telephone or medical records. Continuous variables were compared by student t test or Wilcoxon rank sum test. Quantitative variables were compared by chi-square test. Survival was analyzed by Kaplan-Meier curve. Predictive factors of prognosis was estimated by using Cox regression analysis. Results:One hundred and nine NPSLE patients were included. Thirteen (11.9%) were male and 96 (88.1%) were female with a median age of 33 years old. Central nervous system involvement was predominant (89/109, 81.7%) . The most common types were headache, cerebrovascular disease and epilepsy. Cranial neuropathy was the most common type at the initial onset of systemic lupus erythematosus (SLE) , while cerebrovascular disease was more common when SLE relapsed. Patients who demonstrated NPSLE at the initiation of SLE had shorter survival time than those who got NPSLE when SLE relapsed [ (32±26) months vs (197±79) months, t=2.834, P=0.037]. Among the 105 patients with complete followed up data, the follow up time was 118.0 (1.4, 525.7) months and 53.1 (0.4, 363.0) months from the onset of SLE and NPSLE, respectively. The mortality rate was 14.3% (15/105) . The survival rates of 1-5 years were 96.2%, 94.3%, 91.0%, 89.9% and 88.3%, respectively. The survival time was (180±138) months and (33±32) months, t=3.861 , P<0.01) from the onset of SLE and NPSLE, respectively. The major causes of death were infection, NSPLE and cardiovascular disease. Cerebrovascular disease was the independent risk factor for death [ RR=3.413, 95% CI (1.049, 11.102) , P=0.041]. Conclusion:Cranial neuropathy is the most common type at the initial onset of SLE, while cerebrovascular disease is more common when SLE relapsed. Patients who had NPSLE at the initiation of SLE have shorter survival time than those who got NPSLE when SLE relapsed. Cerebrovascular disease is the independent risk factor of death of NPSLE patients.

Objective: To analyze the relationship between the toilet design and sanitary condition of primary and secondary schools in Chengdu and the epidemic situation of Norovirus infection, so as to provide scientific references for school toilet design and Norovirus prevention and control. Methods: A total of 78 cases of norovirus epidemics from 2019 to 2020 were included in this study. These epidemics happened in 78 schools and the causes were indicated as human-to-human transmission. The Chi square and Mann-Whitney U test were used to compare categorical and continuous data respectively. Unconditional binary Logistic regression was used to examine the multivariate associations. Results: Most epidemics happened from October in 2019 to March in 2020(79.49%, 62 cases), in primary schools (71.79%, 56 cases) and in the center area (52.56%, 41 cases). The median of the case number in each epidemic was 10. Overall, 56 schools (71.79%) were equipped with toilets which were flushed independently, and 22 schools (28.21%) were equipped with toilets which were flushed uniformly. There were 27 schools (34.62%) that did not have enough water taps. Logistic regression analysis found that those with toilets flushed uniformly had a stronger epidemic, compared to the schools with toilets flushed independently( OR=5.53, 95%CI=1.63-18.76, P <0.05). Conclusion In order to prevent intestinal infectious diseases , it is suggested that schools should design or reconstruct independent flushing toilets with adequate faucets.

Purpose: The main goal of this study was to analyze the prognosis of secondary oral squamous cell carcinoma (SCC) with a comparison with sporadic oral SCC by a matched-pair design. Materials and Methods: Records of patients with surgically treated primary oral SCC were reviewed, and a total of 83 patients with previous history of radiotherapy for nasopharyngeal carcinoma (NPC) were retrospectively enrolled. A matched-pair study was performed, each NPC survivor was matched with two sporadic oral SCC patients by age, sex, primary tumor site, adverse pathologic characteristics, disease stage, neck node status, and tumor stage. The overall survival (OS) and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method; independent prognostic factors were evaluated by the Cox proportional hazards method. Results: Compared with sporadic oral SCC patients, NPC survivors were less likely to be smokers (p=0.004), perineural invasion and lymphovascular invasion were more common in NPC survivors (both p < 0.001). The 5-year OS and DSS rates in NPC survivors were 47% and 54%, respectively; the 5-year OS and DSS rates in sporadic oral SCC patients were 62% and 67%, respectively; the difference was significant (both p < 0.05). In survival analysis, disease stage remained to be independent prognostic factor for both the OS and DSS. Conclusion NPC survivors had worse OS and DSS than sporadic oral SCC patients, NPC survivors were less likely to be smokers, but had higher opportunity of perineural invasion and lymphovascular invasion. Disease stage was the most important predictor for the survival in NPC survivors.

OBJECTIVE： To establish a method for concentration determination of sinoacutine in rabbit plasma， and to conduct its pharmacokinetic study. METHODS： The rabbits were grouped according to gender， 6 rabbits in each group. Rabbits were injected with sinoacutine solution （5 mg/kg） via ear vein. Each blood sample 1 mL was collected before medication and 5， 10， 15， 30， 45， 60， 90， 120， 180， 240 min after medcation. After the plasma isolated and extracted with ethyl acetate， HPLC method was adopted by using sinomenine as internal standard. The determination was performed on Agilent Zorbax Extend-C18 column with mobile phase consisted of methanol-2 mmol/L disodium hydrogen phosphate aqueous solution （containing 0.016％ triethylamine， pH 9.8） （45 ∶ 55， V/V) at the flow rate of 1 mL/min. The detection wavelength was set at 262 nm， and column temperature was 30 ℃. The sample size was 20 μL. The pharmacokinetic parameters were calculated by using DAS 3.0 software. The difference of 2 groups were investigated by t-test. RESULTS： The linear range of sinoacutine were 0.1-5.0 mg/L； the limit of quantitation was 0.1 mg/L， and the lowest detection limit was 0.08 mg/L. RSDs of intra-day and inter-day were both less than 10％； the accuracy ranged from （99.80±8.21）％-（103.61±8.55）％. The extraction method did not affect the quantitative analysis of the substance to be measured. The average plasma-time curve of sinomenine with single intravenous injection in rabbits was in line with the two-compartment model. The distribution half-life of all rabbits was （10.99±2.52） min， and the elimination half-life was （147.08±32.41） min. AUC0-t was （190.82±30.82）mg·min/L， and AUC0-∞ was （289.82±73.27） mg·min/L. There was no statistical significance in pharmacokinetic parameters between female and male rabbits （P＞0.05）. CONCLUSIONS： Established HPLC method is simple， specific and sensitive， and can be used for plasma content determination of sinoacutine. Pharmacokinetic study shows that the pharmacokinetic process of the compound is in line with two-compartment model in rabbits. The pharmacokinetic parameters of the compound have no sex difference， and the compound is distributed rapidly and eliminated fast.