In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

OBJECTIVEThe incidence of type 1 diabetes varied in different countries, different nations and different regions. This survey was conducted to clarify the incidence of type 1 diabetes of children in Beijing area between 1997 and 2000, to compare and analyze the difference in incidence of type 1 diabetes between the 2 periods of 1988 - 1996 and 1997 - 2000.

METHODAccording to the criteria of WHO Diabetes Mondial (DIAMOND), data were collected from all the children younger than 15 years of age in Beijing area who had the onset of type 1 diabetes during Jan. 1st, 1997 to Dec. 31st, 2000. Using the capture-recapture methods, 95% confidence intervals of incidence were calculated with Poisson's distribution formula. The significance of differences was tested with Chi-square method.

RESULTSThe incidences of type 1 diabetes during 1997 - 2000 were around 0.76/100 000 to 1.21/100 000. The average yearly incidence was 1.014/100 000 (95% confidence interval was 0.98/100 000 - 1.16/100 000). There was no significant difference in the incidence between 1988 - 1996 and 1997 - 2000, and it showed the same result when the incidences were adjusted by age according to the Chinese population census in 2000 (The incidence was 0.83/100 000 in 1988 - 1996 and 0.86/100 000 in 1997 - 2000, respectively). The incidence was higher in 10 - 14 year-old group than the younger groups (P = 0.002). There was no significant difference between male and female groups, either.

CONCLUSIONSNo significant difference was found between the periods 1988 - 1996 and 1997 - 2000 when the average yearly incidence of type 1 diabetes of children in Beijing was compared. These results were different from the other countries' reports that the incidence of type 1 diabetes was increasing by 3% - 5% per annum. There was no significant difference between male and female groups either and there was a higher incidence of type 1 diabetes in 10 - 14 yr group than the other groups in 1997 - 2000. Although the life-style of Beijing people changed a lot, it didn't affect the incidence of type 1 diabetes in children in this area. But since many people migrated to Beijing from other parts of the country, the changes in constitutive proportions of population might have some impacts on the results of the survey.

Age Factors ; Child ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; epidemiology ; Female ; Health Surveys ; Humans ; Incidence ; Male ; Sex Factors

OBJECTIVETo evaluate the therapeutic effects and adverse effects of transarterial oily chemoembolization combined with interstitial laser thermotherapy (TOCE+ILT) in the treatment of hepatocellular carcinoma.

METHODSTotally 120 patients with hepatocellular carcinoma were randomized into two groups and received interventions with TOCE+ILT or TOCE combined with percutaneous ethanol injection (TOCE+PEI). The treatment was repeated when necessary until the tumor was completely ablated, after which the therapeutic effects were evaluated and the patients were the followed up for observing long-term clinical outcome.

RESULTSOf the 120 patients enrolled in this observation, 105 were followed up for two years (54 in TOCE+ILT group and 51 in TOCE+PEI group). The complete tumor necrosis rate of TOCE+ILT group was significantly higher than that of the TOCE+PEI group (84.8% vs 73.9%,Chi(2)=4.405, P=0.036), and TOCE+ILT was associated with a significantly higher negative conversion rate of AFP positivity (77.8% vs 56.1%, Chi(2)=4.592, P=0.032). The 1-year survival rate were similar between two groups, but the 2-year survival rate was significantly higher in patients with TOCE+ILT (79.6% vs 60.8%, Chi(2)=4.477, P=0.034). The hepatic function was comparable between the two groups before treatment, and 1 week after treatment, the ALT level in patients undergoing TOCE+ILT was significantly lower than that in patients with TOCE+PEI (95.90-/+56.06 U/L vs 116.31-/+45.27 U/L, t=2.04, P=0.043). Post-embolization syndrome was observed in the patients in two groups, but no severe adverse events were found.

CONCLUSIONTOCE+ILT has good therapeutic effects and mild side effects in the treatment of hepatocellular carcinoma.

Carcinoma, Hepatocellular ; therapy ; Chemoembolization, Therapeutic ; Humans ; Hyperthermia, Induced ; Lasers ; Liver Neoplasms ; therapy ; Survival Rate ; Treatment Outcome

Objective:To study the effects of hepatitis B virus DNA mutation at 1762/1764 in the basic core promoter (BCP) on metastasis or recurrence of hepatocellular carcinoma (HCC) after hepalobectomy.Methods:Two-hundred and eleven patients with HCC were included in this study after hepalobectomy.Initial demographic data,clinical history,physical examination,biochemical tests,imaging examination and serum HBV DNA level was recorded.The DNA sequences of the S region and BCP region of HBV was determined by direct sequencing following nested-PCR amplification.Prognostic factors were assessed using a univariate Kaplan-Meier analysis and a multivariate Cox proportional hazards model.Results:Of the 187 HCC cases,119 experienced tumor metastasis or recurrence.The univariate analysis showed that a higher metastasis or recurrence rate was associated with larger tumor size,no intact capsule,positive portal vein tumor thrombosis,higher level of gamma-glutamyl transpeptidase,higher level of HBV DNA and positive BCP mutation.The median metastasis or recurrence time for patients with positive BCP mutation was 9 months (95％ CI:7.922-10.078).Cox analysis indicated that larger tumor size,no intact capsule and positive BCP 1762/1764 double mutations were indepent risk factors for HCC recurrence or metastasis [OR (95％ CI),P:25.946 (2.819-57.149),0.007;8.741 (1.896-21.218),0.033 and 27.966 (8.167-58.132),0.003,repsectively].Conculsion:Infection with HBV carrying the positive BCP 1762/1764 double mutation,initial larger tumor volume as well as no intact capsule around the tumor independently predict the development of HCC metastasis or recurrence and ealier time for metastasis or recurrence after hepalobectomy.

Ligusticum chuanxiong is a well-known traditional Chinese medicine plant. The study on its molecular markers development and germplasm resources is very important. In this study, we obtained 24 422 unigenes by assembling transcriptome sequencing reads of L. chuanxiong root. EST-SSR was detected and 4 073 SSR loci were identified. EST-SSR distribution and characteristic analysis results showed that the mono-nucleotide repeats were the main repeat types, accounting for 41.0%. In addition, the sequences containing SSR were functionally annotated in Gene Ontology (GO) and KEGG pathway and were assigned to 49 GO categories, 242 KEGG pathways, among them 2 201 sequences were annotated against Nr database. By validating 235 EST-SSRs,74 primer pairs were ultimately proved to have high quality amplification. Subsequently, genetic diversity analysis, UPGMA cluster analysis, PCoA analysis and population structure analysis of 34 L. chuanxiong germplasm resources were carried out with 74 primer pairs. In both UPGMA tree and PCoA results, L. chuanxiong resources were clustered into two groups, which are believed to be partial related to their geographical distribution. In this study, EST-SSRs in L. chuanxiong was firstly identified, and newly developed molecular markers would contribute significantly to further genetic diversity study, the purity detection, gene mapping, and molecular breeding.