Objective To evaluate the quality of life (QOL) in adults with epilepsy.Methods The QOLIE-31 and the SDS were administered to 33 adults with epilepsy who met the entry criteria, and 17 healthy volunteers who had the similar personal characters. Results Patients' scores of SDS were adversely associated with seven of the eight QOL domains (except for medication effect) independent of other factors. Duration of the disease was the independent risk factor to overall health and medication effect. The GTC group (17 subjects) and the CPS group (16 subjects) were both obviously compared with the control group in medication effect (GTC group 61.0?23.8,CPS group 56.6?19.4,control 100.0?0.0) and seizure worry domains ( P

Objective To investigate the effect of mice gender on the TSH receptor antibody(TRAb)titers, the levels of TT4,and the degree of thyroid hyperplasia by establishing an animal model of Graves′ disease in male and female BALB/c mice. Methods Male and female BALB/c mice were immunized with recombinant adenovirus expressing TSHRA subunit(Ad-TSHR289)to induce Graves′ disease. Animals were injected 3 times at intervals of 3 weeks. All mice were sacrificed 4 weeks after the last injection to obtain blood for measurement of TSHR antibody titers and TT4evels, and thyroid glands for histological examination. Results TRAb positive rates were 100% both in female or male mice. No significant difference was observed in titers of TRAb between them. The incidence of hyperthyroidism in female mice was higher than that in male mice, being 75.0% and 41.7% respectively. There was statistical difference in levels of TT4between females and males(P＜0.01). Mice with high TT4exihibited marked thyroid hyperplasia. Conclusion Despite TSHR antibodies were similar between female and male mice, the incidence and degree of hyperthyroidism showed sex bias in Graves′s animal model. The results indicated that it was easier to induce model in females than in males by immunizing BALB/c mice with Ad-TSHR289.

Objective To investigate the feasibility of inducing neonatal immunotolerance against Graves'disease by gene TSH receptor (TSHR) 289 and its possible mechanism.Methods Neonatal (0-24 h) female BALB/c mice were divided into intraperitoneal injection group,intramuscular injection group,model group,and normal control group.The intraperitoneal group and the intramuscular group were further divided into low-dosage,middle-dosage,high-dosage tolerance groups,and the coresponding control groups.The tolerance groups and the controls were intraperitoneally or intramuscularly pretreated with low-dosage( 1×106 particles),middle-dosage( 1 × 108particles),high-dosage( 1 × 1010 particles)of Ad-TSHR 289 or Ad-lacz respectively.6 to 7 weeks later,the normal control group received intramuscular injection with Ad-lacz; the other groups were immunized with Ad-TSHR289,three times at 3 weeks interval.10 days after the first immunization,serum TRAb was detected.4 weeks after the last immunization,serum TRAb,TT4,splenic CD4 + CD25 + Foxp3/CD4 + were tested,and the thyroid tissues were examinated histologically.Results Ten days after the first immunization,no antibody response against TSHR was detected in the two high-dose tolerance groups,but the TRAb titer in respective controls was significantly higher( P＜0.05 ).4 weeks after the last injection,in high-dose tolerance groups,only 1/10 of mice immunized by intraperitoneal or intramuscular injection elicited anti-TSHR antibody,and no mice immunized intraperitoneally had elevated serum TT4.Two of ten mice challenged intramuscularly showed slightly increased TT4 levels,but the respective controls displayed a strong antibody response( P＜0.01 ) and elevated TT4 level ( P＜0.05 ).The similar percentages of high TT4 and thyroid hyperplasia were found in all groups.Additionally,the frequencies of CD4+CD25 +Foxp3/CD4+in two high-dose tolerance groups were significantly increased as compared to those in controls( P＜0.05 ).The incidence of Graves' disease in the other groups by intraperitoneal or intranuscular injections was not statistically different from those in the corresponding control groups and the model group.Conclusions The immune tolerance against Graves'disease is induced in neonatal mice by either intraperitoneal or intramuscular pathway with specific antigen of TSHR 289,carried by adenovirus vector,and then inhibits Graves' disease in adults. Stimulation with the high-dosage antigen is liable to induce immune unresponsiveness.CD4 + CD25 + Foxp3 +T cells may play an important role in the induction and maintenance of tolerance.

Objective To compare the efficacy of Graves disease animal models induced by thyroid stimulating hormone receptor (TSHR) plasmid DNA (pcDNA3.1-TSHR) and by TSHR A subunit recombinant adenovirus(Ad-TSHR289),and to investigate the influence of duration for preparing animal model induced by Ad-TSHR289 on Graves hyperthyroidism and its related indices.Methods The plasmid group and the adenovirus group were set up respectively.The plasmid group:21 female BALB/c mice were randomly divided into model group (n =12) and control group (n =9).The model group were injected intradermally with pcDNA3.1-TSHR 50 μg,once every 3 weeks,totally 3 times.Then 4 weeks after the last immunization,the mice were euthanized to obtain blood for testing TSHR antibody (TRAb),total T4,and thyroid tissue for histological examination.The controls were injected with the same dose of pcDNA3.1 in the same way.The adenovirus group:52 female BALB/c mice were divided into 10-week model group (n =8),14-week model group (n =10) and 18-week model group (n =8),and the respective controls (n =8,n =10,n =8) were set up.All model groups were injected intramuscularly with Ad-TSHR289,three times at three weekly intervals.Then the mice were euthanized at 4,8 and 12 weeks to test TRAb,total T4 level and to observe the change of thyroid histology.The controls were treated with the same dose of Ad-lacz in the same way.Another 8 mice were scheduled to test the dynamic variation of TRAb before and after the 3 times immunization.Results In the plasmid model group,only two of 12 mice developed weak antibody responses against TSHR,and no elevated total T4 level and no hyperplasia changes of thyroid were observed.In the 10-week model group,all mice had high level TRAb [(807.65 ± 136.33)U/L,Six-eighths mice had hyperthyroidism exhibited hyperplasia changes.In the 14-week model group,the TRAb level [(650.12 ± 192.88) U/L]and the incidence of hyperthyroidism (3/10) were lower than those in 10-week group.Histologically,the degree of thyroid hyperplasia lightened to a small extent,but its positive rate did not decline.In the 18-week model group,only 2 of 8 mice displayed slightly elevated TRAb level,and no mice showed increased total T4 level.Additionally,thyroid tissues of 2 mice were mildly abnormal.Compared with the model groups at different time,the change of antibody levels of the mice for TRAb dynamic observation exhibited the similar trend.Conclusions Being good at repeatability and high incidence of hyperthyroidism,the animal model of Graves disease induced by Ad-TSHR289 is still an ideal research tool presently.The duration of model ean be maintained 18 weeks,and 10 weeks is the best period to snstain characteristic of Graves disease.

A rapid,sensitive,and robust reversed-phase liquid chromatography with tandem mass spectrometrymethod was developed and validated for the determination of total and unbound ceritinib,a secondgenerationALK inhibitor,in patient plasma and brain tumor tissue samples.Sample preparation involvedsimple protein precipitation with acetonitrile.Chromatographic separation was achieved on a Waters ACQUITYUPLC BEH C18 column using a 4-min gradient elution consisting of mobile phase A(0.1% formic acidinwater)andmobile phase B(0.1% formic acid in acetonitrile),at a flow rate of 0.4 mL/min.Ceritinib and theinternal standard([13C6]ceritinib)were monitored using multiple reaction monitoring mode under positiveelectrospray ionization.The lower limit of quantitation(LLOQ)was 1 nM of ceritinib in plasma.The calibrationcurve was linear over ceritinib concentration range of 1–2000 nM in plasma.The intra-and interdayprecision and accuracy were within the generally accepted criteria for bioanalytical method(<15%).The method was successfully applied to assess ceritinib brain tumor penetration,as assessed by the unbounddrug brain concentration to unbound drug plasma concentration ratio,in patients with brain tumors.

Abstract: Objective　To evaluate the completion and final effect of key parasitic disease prevention and control planning tasks in Hubei Province from 2016 to 2019, summarize the experience, find out the problems, and provide the basis for the next stage of prevention and control. Methods　According to the requirements of the Final Evaluation Plan of the National Plan for the Prevention and Control of Hydatid Disease and Other Major Parasitic Diseases (2016-2020), a retrospective survey method was adopted to collect relevant data on the implementation and safeguard measures of the prevention and control of major parasitic diseases, and population infection status in Hubei Province in 2016-2019. Results From 2016 to 2019, We carried out 2 920 992 person times of publicity and education, 209 times of prevention and control technology training, 7 680 person times of business training, with an average of 52 sessions and 1 920 person times per year. We have allocated 3.445 2 million yuan for the prevention and control of parasitic diseases, including 1.722 2 million Yuan froom provincial government, to achieved full coverage of safe drinking water in rural areas under the current national standards, and 7.687 9 million harmless toilets have been built in rural areas. From 2016 to 2019, we carried out 39 658 person times of monitoring and disease investigation, the infection rate of human liver fluke was 0, and the infection rate of soil transmitted nematode was 0.42%. While the annual infection rates varied, there was no statistically significant difference in infection rate between years (χ2＝2.276, P>0.05), but there were statistically significant differences in the infection rates between various soil nematodes (χ2=112.807, P<0.01). From 2016 to 2019, a total of 5 393 people were detected at 17 monitoring points, with the serum positive rate of 3.93% for paragonimiasis, there was a statistically significant difference in serological positive rate between years (χ2=146.011, P<0.01); a total of 738 stream crabs were collected, and the infection rate of intermediate host was 16.26%, wtih a statistically significant difference in the infection rate of stream crabs between years (χ2=49.731, P<0.01). Conclusions　From 2016 to 2019, we adhered to the prevention and control strategy of "prevention first, prevention and control combined", implemented comprehensively various prevention and control measures, and achieved remarkable results in Hubei Province. The key parasitic diseases have been in a low epidemic situation, meeting the requirements of the prevention and control objectives. But the transmission risk still exists, the next step is to continue to strengthen security and monitoring and consolidate the achievements of prevention and control.

OBJECTIVE Ginsenoside metabolite compound K (CK) is a degradation product of ginsenoside in the intestine by bacteria. The anti-inflammatory and immunomodulatory activities of CK have been reported. This study investigated whether CK exerted its immunoregulatory effect through modulation of dendritic cells (DCs) function. METHODS In vivo, severity of collegen-induced arthritis (CIA), T cells and DCs subsets, phenotype of DC were assayed by flow cytometry, CCL19 and CCL21 level in lymph nodes assayed by ELISA. In vitro, bone marrow-derived DCs from normal mice were matured with lipopolysaccharide and treated with CK for 48 h. In vivo, bone marrow-derived DCs were generated from CIA mice before and 2 weeks into CK treatment. DCs were analyzed for migration, phenotype and T- cell stimulatory capacity. RESULTS CK alleviated the severity of CIA, decreased pDCs and mo-DCs, increased na?ve T cells in CIA mice lymph nodes, and suppressed CCL21 expression in lymph nodes. CK suppressed DCs migration induced by CCL21 and T cells-stimulatory capability of DC, down-regulated LPS-induced expression of CD80, CD86, MHCII and CCR7 on DCs. CONCLUSION This study elucidated the novel immunomodulatory property of CK via impairing function of DCs in priming T cells activation. These results provide an interesting novel insight into the potential mechanism by which CK contribute to the restoration of immunoregulation in autoimmune conditions.

OBJECTIVETo observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy.

METHODSTotally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared.

RESULTSDifferent treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both).

CONCLUSIONSBoth constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.

Antiviral Agents ; therapeutic use ; Gene Frequency ; HLA-DQ alpha-Chains ; genetics ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; genetics ; Humans ; Interferon-alpha ; therapeutic use ; Medicine, Chinese Traditional ; Polyethylene Glycols ; therapeutic use ; Polymorphism, Genetic ; Recombinant Proteins ; therapeutic use ; Remission Induction ; Yin Deficiency ; genetics

Abstract: Objective　To collect and organize malaria case data in Hubei Province from 2017 to 2021, compare and analyze the malaria epidemic characteristics on the before and after malaria elimination, and provide scientific support for Hubei Province to further optimize the comprehensive strategies to prevent re-transmission after the elimination of malaria. Methods The study was conducted by collecting the data of reported malaria cases of Hubei during 2017-2021 from the Infectious Disease Surveillance Reporting and Management System, and conducting the epidemiological characteristics of malaria on pre-elimination (2017-2019) and post-elimination (2020-2021). Results A total of 429 cases of imported malaria were reported in Hubei Province from 2017 to 2021, and the malaria epidemic showed an obvious trend of rising first and then falling. On the pre-malaria elimination, 374 malaria cases were reported, including 262 cases of P.falciparum (70.05%); on the post-malaria elimination, 55 malaria cases were reported, including 25 cases of P.falciparum (45.45%). There was a statistically significant difference in the proportion of infections caused by the four types of malaria parasites before and after the elimination of malaria (χ2=14.248, P<0.05). On the pre-malaria elimination, the peak of disease onset mainly occurred in January, July, and November; on the post-malaria elimination, the peak of disease onset mainly occurred in January to February, and December. Both before and after malaria elimination, the reported cases were mainly concentrated in Wuhan, Yichang, Huangshi, Xiangyang, Shiyan and Huanggang, but the range of cases showed a clear trend of narrowing. Before and after malaria elimination, malaria cases in Hubei Province were mainly among young and middle-aged males aged 30-49. The proportions of workers and migrant workers increased from 37.70% and 9.09% before the elimination to 50.91% and 18.18% after the elimination, respectively, with a statistically significant difference (χ2=17.839, P<0.05). The percentage of interval from onset of illness to initial diagnosis ≥ 5d decreased from 21.66% before the elimination to 10.91% after the elimination (χ2=6.448, P<0.05). The percentage of definitive diagnosis of malaria at initial diagnosis in town clinic increased from 18.18% before the elimination to 50.00% after the elimination. The proportion of malaria cases diagnosed by county-level medical institutions increased from 22.73% before the elimination to 34.55% after elimination. There was no statistically significant difference in the proportion of malaria cases diagnosed by medical institutions at all levels before and after the elimination of malaria (χ2=5.630, P>0.05). The proportion of cases with the interval between initial diagnosis and diagnosis within 24h increased from 43.85% before the elimination to 70.91% after the elimination. There was a statistically significant difference in the proportion of cases with the interval between initial diagnosis and diagnosis before and after the elimination of malaria (χ2=14.006, P<0.05). Before and after malaria elimination, all reported cases were mainly imported from African countries. Conclusions There are imported malaria cases reported every year in Hubei Province before and after the elimination of malaria, which poses a great challenge to the prevention of re-transmission. Therefore, it is necessary to strengthen the surveillance system, detect and standardize the treatment of imported malaria cases in a timely manner, conduct targeted retransmission risk surveys and assessments, and consolidate the achievements of malaria elimination.

Objective To assess the clinical value of HPV genotyping in follow-up after treatment for cervical high grade squamous intraepithelial lesion (HSIL). Methods Two hundred and thirty eight patients with HSIL receiving conization in Cancer Hospital, Chinese Academy of Medical Sciences from Dec, 2006 to Jan, 2009 were accrued in our study. All the patients were prospectively observed after conization every 6 months for 3 times or till histologically confirmed recurrence. The items in every visit included pelvic examination, cervical cytology and HPV genotyping. Twenty-one HPV genotypes were detected by PCR-hybridization method. The last follow-up was July 31, 2010, and the median follow-up time was 28.3 months (range 6.5-43.0 months). Kaplan-Meire method as used for analyzed the median recurrent time, and the relationships between HPV status and recurrent disease were calculated by and log-rank test and Cox-regression model. Results Among the 238 patients, 110 cases (46.2%, 110/238) had positive result of HPV DNA testing at any visit. The most common HPV types detected in follow-up were HPV16 (45.6%), HPV58 (26.5%), and HPV52 (16.9%). There was no correlation between recurrent disease and any individual high risk HPV infections (P>0.05). Seventeen recurrent cases (7.1%) were identified in 238 patients within a median recurrent time of 14.9 months (range 6.0-32.1 months). In univariate analyses, HPV positive at any visit, persistent infection, multiple infection, type specific persistent infection and positive HPV at 18 months after conization were indicators for residual/recurrent disease (P<0.05). In multivariate analysis, only multiple HPV infection (HR=8.6, 95%CI:1.8-41.7, P=0.008) and type specific persistent HPV infection (HR=5.1, 95%CI: 1.0-24.8, P=0.042) had an elevated risk of recurrent disease. Conclusions HSIL with multiple HPV infection and type specific persistent HPV infection in follow-up are at high risk of recurrent disease. Patients with HPV turning into negative within 18 months after treatment have a low risk of recurrence.