Objective To investigate the awareness of radon exposure hazards among non-uranium miners in Chongqing, China. Methods A survey was conducted among 177 male miners from eight non-uranium metal mines in Chongqing to collect data on basic information, personal habits, and the rate of radon awareness. Factors affecting radon awareness were analyzed using chi-square test and logistic regression model. Results The awareness rate of radon among miners was 23.73%. The chi-square test indicated significant difference in the radon awareness rate among miners with different levels of education (χ² = 10.28, P < 0.05), while there was no significant difference across different ages, years of work, labor relations, job categories, and types of miners (P > 0.05). Binary logistic regression analysis showed that a college (junior college) or higher level of education, a high school level of education, and working in mines were factors affecting the radon awareness among miners (χ² = 4.030, 9.150, 11.776, P < 0.05). Conclusion Miners lack awareness of radon, and there is an urgent need to strengthen education and propaganda regarding the hazards of radon.

Objective:To identify micronuclei through the cytochalasin B blocking micronucleus method-based assay using scanning microscope, combined with the slide scanning software Metafer 4 and, accordingly, to establish a dose-response relationship between the dose of 60Co γ-rays and the frequency of micronuclei in human peripheral blood lymphocytes using artificial intelligence-based color recognition. Methods:Blood samples were collected from four healthy individuals (two men and two women) and were then exposed to varying doses of 60Co γ-ray radiation (0, 0.25, 0.5, 1, 2, 3, 4, 5 Gy) at a dosage rate of 0.74 Gy/min. Micronucleus slides were prepared as per the GBZ 128-2023 standard. The numbers of binuclear cells and micronuclei were recorded using an artificial intelligence-based color recognition analysis system. The dose-response curve was determined through fitting using the CABAS software. Then, the doses to both independent samples were estimated based on the curve. Results:Within a dose range of 0 to 5 Gy, the fitted micronucleus dose-response curve aligned with a quadratic polynomial model, with a regression equation of y = 0.032 1 D2+ 0.023 7 D+ 0.012 7 ( D denoting the dose, correlation coefficient R2=0.998). The dose estimations from the validation samples closely corresponded to the actual irradiation doses. Conclusions:Establishing the micronucleus dose-response curve provides a feasible method and basis for the rapid and accurate estimation of radiation biological doses in laboratory automation.

Objective To investigate the therapeutic effect of Euryale ferox seed shell extract on oral ulcer in rats and its underlying mechanism. Methods The contents of polyphenols and flavonoids in Euryale ferox seed shells were determined by Folin-phenol assay and aluminum nitrate colorimetry, respectively. DPPH · , ABTS+· , · OH and · O2- scavenging experiments were performed to evaluate the antioxidant activities of Euryale ferox seed shell extract in vitro. In a rat model of oral ulcer induced by burning with glacial acetic acid, the therapeutic effect of Euryale ferox seed shell extract was assessed by detecting changes in serum levels of oxidative factors by enzyme-linked immunosorbent assay (ELISA) and observing pathological changes of the ulcerous mucosa using HE staining; the therapeutic mechanism of the extract was explored by detecting the expression levels of Keap1, Nrf2, Nes-Nrf2 and HO-1 proteins in ulcerous mucosa using Western blotting. Results The ethyl acetate extract of Euryale ferox seed shells contained 306.74±1.04 mg/g polyphenols and 23.43±0.61 mg/g flavonoids and had IC50 values for scavenging DPPH · and ABTS+· free radicals of 3.42 ± 0.97 μg/mL and 3.32 ± 0.90 μg/mL, respectively. In the rat models, the ethyl acetate extract significantly ameliorated oral mucosal ulcer, increased serum CAT level, and decreased serum MDA level. The protein expression levels of Nes-Nrf2 and HO-1 were increased and Keap1 protein expression was lowered significantly in the ulcerous mucosa of the rats after treatment with the extract (P<0.05 or 0.01). Conclusion The therapeutic effect of Euryale ferox seed shell extract on oral ulcers in rats is mediated probably by activation of the Keap1/Nrf2/HO-1 signaling pathway.

Objective : Mendelian randomization analysis was used to explore the causal relationship of T．gondii in- fection and the cyst distribution and inflammation in brain tissue by immunohistochemistry． Methods : Genome- wide association analysis data of T．gondii infection and encephalitis were obtained ，single nucleotide polymor- phisms (SNPs) were selected，Mendelian randomization analysis was conducted by inverse variance weighting，and the causal relationship between T．gondii infection and encephalitis was evaluated by OR value and 95% CI．Quality control was carried out by using heterogeneity test，horizontal multi-efficiency test and leave-one-out sensitivity test. Immunohistochemical staining was performed using brain sections of mice infected with tissue cysts of Wh6 strain for image analysis using Image J software. Results : A total of 29 SNPs were associated with toxoplasmic encephalitis. The results of IVW method suggested that T．gondii infection made encephalitis risk 0. 98 times higher ( OR = 0. 98， 95% CI = 0. 76 to 1. 27) ，indicating no causal relationship between the two．The quality control results suggested that the selected SNPs were stable and reliable．Toxoplasma cysts were distributed in various parts of the brain tis- sue． Conclusion T．gondii infection and encephalitis are related，but there is no sufficient evidence to prove the causal relationship between the two.

Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

Objective To investigate the therapeutic effect of Euryale ferox seed shell extract on oral ulcer in rats and its underlying mechanism. Methods The contents of polyphenols and flavonoids in Euryale ferox seed shells were determined by Folin-phenol assay and aluminum nitrate colorimetry, respectively. DPPH · , ABTS+· , · OH and · O2- scavenging experiments were performed to evaluate the antioxidant activities of Euryale ferox seed shell extract in vitro. In a rat model of oral ulcer induced by burning with glacial acetic acid, the therapeutic effect of Euryale ferox seed shell extract was assessed by detecting changes in serum levels of oxidative factors by enzyme-linked immunosorbent assay (ELISA) and observing pathological changes of the ulcerous mucosa using HE staining; the therapeutic mechanism of the extract was explored by detecting the expression levels of Keap1, Nrf2, Nes-Nrf2 and HO-1 proteins in ulcerous mucosa using Western blotting. Results The ethyl acetate extract of Euryale ferox seed shells contained 306.74±1.04 mg/g polyphenols and 23.43±0.61 mg/g flavonoids and had IC50 values for scavenging DPPH · and ABTS+· free radicals of 3.42 ± 0.97 μg/mL and 3.32 ± 0.90 μg/mL, respectively. In the rat models, the ethyl acetate extract significantly ameliorated oral mucosal ulcer, increased serum CAT level, and decreased serum MDA level. The protein expression levels of Nes-Nrf2 and HO-1 were increased and Keap1 protein expression was lowered significantly in the ulcerous mucosa of the rats after treatment with the extract (P<0.05 or 0.01). Conclusion The therapeutic effect of Euryale ferox seed shell extract on oral ulcers in rats is mediated probably by activation of the Keap1/Nrf2/HO-1 signaling pathway.

ObjectiveTo explore the effects and possible mechanisms of Jianpi Bushen Formula （健脾补肾方） on radiation-induced immune function damage of mice. MethodsFifty mice were randomly divided into four groups： normal group， model group， thymosin group， high- and low-dose groups of Jianpi Bushen Formula， with 10 mice in each group. Except for the normal group， the mice in the other groups were irradiated with a single whole-body dose of 6.0 Gy X-rays to establish a radiation-injured mouse model. After the successful modeling， the low- and high-dose groups of the Jianpi Bushen Formula were given respectively 13 g/（kg·d）、 26 g/（kg·d） of the formula by gavage， while the thymosin group was given 11.7 mg/（kg·d） of thymosin by gavage， and the normal group and model group were given 0.1 ml/（10g·d） of 0.9% sodium chloride solution by gavage. Each group was administered once a day for 7 consecutive days. After the last gavage， the mice were weighed， and their spleens were separated and weighed to calculate the spleen index. The levels of interferon gamma （IFN-γ） and interleukin 2 （IL-2） in the spleen tissue were detected by enzyme linked immunosorbent assay （ELISA）. The autophagosomes in the spleen were observed by transmission electron microscopy. The mRNA expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR） in the spleen were detected by real-time fluorescent quantitative PCR. The protein expression of PI3K， Akt， and mTOR in the spleen， as well as the expression of autophagy-related proteins microtubule-associated light chain protein 3 （LC3）， Beclin1， and p62 were detected by Western blot. ResultsCompared with the normal group， the model group showed significant decreases in body weight， spleen index， and levels of IFN-γ and IL-2 in the spleen （P＜0.01）； the mRNA and protein expression levels of PI3K， Akt， and mTOR in the spleen were also significantly reduced （P＜0.01）； the expression of Beclin1 protein， the ratio of LC3-II/LC3-I significantly increased （P＜0.01）， while the level of p62 protein expression significantly decreased （P＜0.01）. And transmission electron microscopy showed a significant increase in the number of autophagosomes in the spleen and severe cell structure damage in the model group. Compared with the model group， all the above indicators in each medication group were significantly improved （P＜0.05 or P＜0.01）. In the high-dose Jianpi Bushen Formula group， partial intact cristae were visible in the fine mitochondria of the spleen， and there were more autophagosomes. In the low-dose Jianpi Bushen Formula group and thymosin group， the structure of the fine mitochondria in the spleen was relatively intact， and there were fewer autophagosomes. The improvement effect of the low-dose Jianpi Bushen Formula group was better than that of the high-dose group （P＜0.05 or P＜0.01）， and there was no significant difference between the low-dose group and the thymosin group in terms of each indicator （P＞0.05）. ConclusionJianpi Bushen Formula may alleviate the structural damage of the spleen， promote the recovery of immune function， and achieve a best effect at a low dose by enhancing the PI3K/Akt/mTOR signaling pathway in the spleen and inhibiting the over-activation of autophagy induced by radiation.

Objective: To investigate the distribution of toxoplasma cysts in the brain of infected mice and the effect of pathological changes on the behavior and neuropsychiatry of the mice during chronic infection with Toxoplasma gondii( T．gondii) ． Methods : Mice were infected with Prugniaud strain of T．gondii by oral gavage．The brain tissues of infected mice were collected on the days of 10，30，40，90，120 and 160 after infection respectively，and the hippocampal hypothalamus，prefrontal lobe ，striatum and cerebellum regions were separated．The number of cysts and neuropathological changes in each infected area were observed and recorded by HE staining．The number of cysts and neuropathological changes in each infected area were observed and recorded. Results : T．gondii infected mice showed symptoms of vertical hair and arched back，which were the most significant on the 40th day，and then gradually recovered with hemiplegia and circling in circles． At each time point ，the number of toxoplasma cysts was the largest in hippocampal hypothalamus，followed by prefrontal lobe and striatum，and the least in cerebellum．The diameter of toxoplasma cysts increased with time．During chronic infection，specific pathological manifestations of toxoplasma encephalitis，such as neuronophagy，were observed in all regions of the brain tissue．The above pathological changes of toxoplasma encephalitis reached the peak on the 40th day，and gradually recovered， and increased to the stimulation peak on the 120th day，and then gradually recovered． Conclusion The behavioral and neuropsychiatric symptoms of T．gondii during chronic infection were correlated with the localization and distribution of toxoplasma cysts in the brain of infected mice，and showed dynamic changes.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Objective:To study the effect of occupational X-ray exposure on non-cancer diseases of radiation workers.Methods:The medical X-ray workers in Chongqing mumicipality were surved in 1980. In 2020, the previous 91 medical institutions distributed across 41 districts and counties of Chongqing continued to be selected as the survyed units, including 53 grade-A top-class hospitals. Using the method of prospective cohort study, the fifth follow-up survey was conducted for Chongqing′s medical X-ray workers and the control groups in 1980 with respect to their personal information, occupational radiation exposure, disease history and others. The incidence rate, relative risk ( RR) and 95% confidence interval of diseases in each system were analyzed. Results:There were 937 individuals in this cohort. So far, 359 cases of non-cancer diseases had been counted. Compared with the control group, the relative risk RR of cardiovascular system, ophthalmology and other unclassified diseases in the exposure group were 1.50, 2.03 and 2.64 ( χ2=5.97, 3.97, 4.25, P <0.05) , respectively. The adjusted confounding factors showed that the RR of the incidence rate of cardiovascular, ophthalmic and digestive diseases in the female exposure group was generally higher than that in the control group ( RR=2.33, 2.59, 7.55; χ2= 7.28, 4.17, 8.64, P < 0.05) , respectively. The RR of the incidence rate of cardiovascular and ophthalmic diseases in exposure group was generally higher than that in the control group among 25-29 year-old workers ( RR=2.26, 5.07; χ2 =8.22, 4.91, P < 0.05) , respectively. For compasion between the the accumulated dose groups, the incidence rate of cardiovascular system, ophthalmology and digestive system diseases in the exposure group was generally higher than that in the control group ( RR=1.86, 2.91, 3.59; χ2= 9.83, 8.21, 5.58, P < 0.05) , respectively. Conclusions:The non-cancer risk of X-ray workers exposed to long-term occupational exposure was increased, among which the risk of cardiovascular system, digestive system, ophthalmic diseases and others might be related to the occupational exposure.