Objective To explore the interaction of calcitonin receptor (CTR) gene polymorphisms and environmental factors in the population lived in coal-burning-borne endemic fluorosis areas in Chongqing.Methods A 1 ∶ 1 case-control study was carried out and Duping Township of Wushan County and Xinglong Township of Fengjie County of Chongqing were chosen as the endemic fluorosis areas.The observation subjects were divided into case group 121 cases and internal control group 130 cases.The Alu I polymorphism in the CTR gene was genotyped using the PCR-RFLP procedure.Logistic regression model was used to analyze the environment and genetic factors,and the interaction between genes and environment was determined according to interaction indicators.Results The rate of CC genotype in case group was lower than that of the control group [60.33％ (73/121) vs.74.62％ (97/130)],while the TT genotype was higher than that of the control group[9.09％ (11/21) vs.3.85％(5/130)].Significant differences in Alu I genotypes were observed between groups(x2 =6.57,P =0.037 ＜ 0.05; 95％CI:0.029-0.036).Allele frequencies of CTR genotypes differed significantly between groups(x2 =7.67,P =0.006 ＜ 0.01 ; OR =0.53,95 ％ CI:0.338-0.834).Urinary fluoride level (≥ 1 mg/L) was demonstrated to be a risk factor of fluorosis(OR =1.814,P =0.041 ＜ 0.05).There was a positive interaction(OR =5.530,γ =2.457) between CT + TT genotypes in CTR and the fluorosis environment of the people (urinary fluoride level ≥ 1 mg/L).Conclusions There is a certain type of interaction between CTR gene C/T polymorphism and environmental fluorine content (urinary fluoride ≥ 1 mg/L) in Chongqing population lived in coal-burning-borne fluorosis areas,and the onset of fluorosis is the result of interaction between heredity and environment.

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

Objective To investigate the anti-tumor activities of cell-penetrating peptide ( CPP) - mediated trichosanthin ( TCS) , which is a recombinant protein obtained from Radix Trichosanthis. Methods Cysteine residue was introduced to the C-terminus of TCS by protein recombinant technique, and then with the newly-formed terminal as the modification site, TCS was coupled with CPP. As a target protein, CPP-mediated TCS was isolated and purified by affinity chromatography. The expression of the target protein and its responsiveness to reducing substances were detected by using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The cellular uptake rate of CPP-mediated TCS was determined by using cell uptake test, and its anti-tumor activity was measured by using methyl thiazolyl tetrazolium (MTT) assay. Results The TCS-CPP compound had been successfully developed in this study, and showed certain reducing responsiveness. After modified with CPP, TCS had higher cellular uptake rate and stronger anti-tumor effect on HeLa and MCF-7 cells. Conclusion TCS modified by CPP can enhance the anti-tumor activities of TCS.

Objective To identify signals of adverse events associated with vaccines in electronic medical record data. Methods Data cleaning was performed on electronic medical records and vaccination data in Gansu Province from 2020 to 2022. Signal identification was performed using Apriori algorithm and Empirical Bayes Gamma-Poisson Shrinker (GPS) with stratification by gender and age group. Results A total of 33 statistical signals were identified, with 7 signals identified by the Apriori method and 26 signals identified by the GPS method. No overlapping signals were found between the two methods at two different signal thresholds. Conclusion The vaccine safety signals identified by GPS and Apriori in electronic medical records are reliable and accurate, but further research is needed to determine the correlation between the vaccine safety signals recognized by GPS algorithms.

Objective: To construct Bayes discriminant function for clinical classification of common and severe Japanese encephalitis (JE) cases, and to identify cases accurately with quantitative indicators. Methods: Samples of confirmed common and severe JE cases reported by the epidemic surveillance system of Gansu Provincial Center for Disease Control and Prevention from 2005 to 2017 were collected. Non-conditional logistic regression analysis and Bayes stepwise discriminant analysis were used to screen meaningful clinical indicators, so as to construct and evaluate Bayes discriminant function. Results: There were 256 common JE cases and 257 severe JE cases. There were no significant differences in sex, age and occupation distributions between the two groups (P>0.05) and there was significant difference in case fatality rate (P<0.05). Non-conditional logistic regression analysis and Bayes stepwise discriminant analysis, combined with using related literature, to screen 11 clinical indicators for the construction of Bayes discriminant function. Interactive validation showed that the sensitivity of discriminant function was 71.48% (95%CI: 65.53%-76.93%) and the specificity was 73.93% (95%CI: 68.11%-79.19%). The area under ROC curve was 0.761 (95%CI: 0.720-0.803) and the total accuracy rate was 72.71%. Conclusion Bayes discriminant function can be used to identify common and severe JE cases more accurately, which is helpful for the reasonable treatment and good prognosis of JE patients.

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.