The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective:To analyze the relationship between dietary composition of residents in endemic fluorosis areas and skeletal fluorosis.Methods:A case-control study was used to analyze the difference of dietary composition between patients with skeletal fluorosis (case group) and residents without skeletal fluorosis (control group). In August 2019, taking the drinking water-borne endemic fluorosis area in Wenshui County, Lvliang City, Shanxi Province as the survey site, a cluster sampling method was adopted to select local residents aged over 18 years old, and a questionnaire survey was conducted by face-to-face interview. The survey contents included gender, age and consumption frequency of various foods. Binary logistic regression was used to analyze the relationship between food consumption frequency and skeletal fluorosis. The diagnosis of skeletal fluorosis was made by using portable digital radiography (DR) to take X-ray films of forearm and lower leg, combining with clinical signs, and according to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008) to determine.Results:A total of 1 061 subjects were included in this study, including 376 in the case group and 685 in the control group. The age composition of patients in the case group (≤60, > 60 years old: 162, 214 cases) was significantly different from that in the control group (≤60, > 60 years old: 423, 261 cases, χ 2 = 34.52, P < 0.001). There was no statistically significant difference in gender ratio (χ 2 = 1.37, P = 0.251). The proportion of patients in the case group who ate meat and eggs > 1 time/week was lower than that in the control group (χ 2 = 8.06, 5.46, P < 0.05), the proportion of patients who ate milk > 1 time/week was higher than that in the control group (χ 2 = 4.01, P = 0.046), and the proportion of patients who ate seafood ≥1 time/week was lower than that in the control group (χ 2 = 4.16, P = 0.046). The results of binary logistic regression analysis showed that after adjusting for age, sex, and urinary fluoride, the frequency of eating meat, eggs or milk > 1 time/week and the frequency of eating seafood ≥1 time/week were not related to the risk of skeletal fluorosis ( P > 0.05); however, in the group ≤60 years old, the frequency of eating eggs > 1 time/week was associated with the risk of skeletal fluorosis [odds ratio ( OR) = 0.59, 95% confidence interval ( CI): 0.39, 0.88]. Conclusions:The consumption frequency of meat, milk, eggs and seafood is significantly different between the skeletal fluorosis patients and the control people. In the population ≤60 years old, consumption frequency of eggs > 1 time/week may reduce the risk of skeletal fluorosis.

Objective To investigate the hemoglobin (Hb) levels during pregnancy and Hb changes from early pregnancy and association with birth weight on infants.Methods Mothers of Zhuang Nationality who participated in the pregnancy care program and delivered at the Pingguo County Hospital from May 2013 to May 2015 were included in this study.Retrospective analysis was applied to collect data of health care and pregnancy outcomes.Multiple regression analysis and unconditional logistic regression model were used for data analysis.Results The mean birth weight appeared as (313 5.92± 435.84) grams.The Hb levels at early pregnancy showed significantly positive association with birth weight.Results from our study demonstrated that when Hb levels increased +1 g/dl at early pregnancy,birth weight would increase 17.61(95％CI:0.60-34.67) grams,in the adjusted model.The Hb levels at late pregnancy were significantly inversely associated with birth weight.Our findings suggested that when Hb levels increased + 1 g/di at late pregnancy,birth weight would reduce 19.61(95％ CI:-37.53--1.70) grams in the adjusted model.Changes in Hb from early pregnancy stages were significantly inversely associated with birth weight after adjusting for confounders and Hb levels in the early pregnancy stages.The results also indicated that when Hb levels increased a + 1 g/dl from early to late pregnancy,the birth weight would decrease 32.63 g(95％ CI:-48.93--16.32).Compared to the non-anemia group,the anemia group showed significantly increase of small-for-gestational-age (SGA)(OR=1.58,95％CI:1.08-2.32) in early pregnancy.Compared to women under the most reduction status,women with the least reduction had a significantly increase of SGA (OR=1.87,95％CI:1.24-2.81) among their infants.With the magnitude of reduction on Hb concentration during pregnancy,the risk of delivering babies with SGA showed a gradual trends of increase.Conclusion Hb levels at early pregnancy were positively associated with birth weight,but the changes of Hb were inversely associated with birth weight at late pregnancy,in women of Zhuang Nationality.Anemia in early pregnancy and the low amplitude of decreased Hb concentration during pregnancy were both risk factors for newborns under less gestational ages.