Hepatitis B virus （HBV） is a unique hepatotropic DNA virus that forms covalently closed circular DNA within the nucleus of hepatocytes and can partially integrate into the host genome， establishing the molecular basis for persistent viral infection. HBV infection and replication depends on multiple hepatocyte-enriched host factors and is modulated by the hepatic microenvironment. The host achieves natural control and clearance of HBV through various mechanisms， including cytolytic elimination mediated by cellular immunity such as cytotoxic T lymphocytes and natural killer cells， innate immunity and noncytolytic clearance driven by interferons and various cytokines， and antibody-mediated protection and clearance as part of humoral immune response. In addition， intracellular restriction factors and pathways， hepatocyte turnover through division and replacement， and changes in the hepatic microenvironment （such as the increase in matrix stiffness） collectively influence the efficiency and outcome of viral control and clearance. This article clarifies and elaborates on related mechanisms， so as to deepen the understanding of HBV chronicity， spontaneous resolution， and cure and provide a theoretical basis for optimizing clinical management and developing novel therapeutic strategies.

At the end of 2020, the FDA issued emergency use authorization for two mRNA vaccines（BNT162b2 and mRNA-1273）, which had provided important support in the response to the COVID-19 pandemic. The great success of these COVID-19 vaccines based on non-viral vectors has promoted the research and application of mRNA vaccines in the treatment of diseases such as tumors. Compared with virus-based delivery systems, non-viral carriers have significant advantages in biological safety and versatility. Therefore, non-viral vectors have become a research hotshot for mRNA tumor vaccines. In this paper, the latest research progress on lipid nanoparticles, polymers, peptides and inorganic materials were introduced. In addition, recent clinical trials of mRNA tumor vaccines were reviewed and the challenges and prospects of non-viral vectors in clinical transformation of mRNA tumor vaccines were discussed.

Objective To investigate the effects of low-dose ionizing radiation on the thyroid status and hormone levels of radiation workers. Methods Radiation workers who underwent occupational health examinations at a hospital in Guangzhou from 2015 to 2022 were selected as the subjects of this study. The levels of FT3, FT4 and TSH were analyzed, and the thyroid abnormality status of radiation workers in different groups were compared. Results A total of 1152 participants were included in this study, consisting of 885 (76.82%) males and 267 (23.18%) females, with an average age of (35.26 ± 10.16) years. The prevalence of thyroid abnormalities was 9.38%, which was significantly higher in females (13.86%) than in males (8.02%) (P < 0.05). The TSH level of females [(2.15 ± 1.29) mIU/L] was higher than that of males [(1.85 ± 1.20) mIU/L], while the levels of FT3 [(5.10 ± 0.64) pmol/L] and FT4 [(15.84 ± 2.32) pmol/L] in females were lower than those in males [(5.23 ± 0.63) pmol/L and (16.61 ± 2.75) pmol/L, P < 0.05]. The FT3 of industrial workers [(5.25 ± 0.63) pmol/L] was higher than that of medical workers [(5.10 ± 0.63) pmol/L], while the TSH of industrial workers [(1.80 ± 1.12) mIU/L] was lower than that of medical workers [(2.15 ± 1.37) mIU/L]. FT4 levels decreased with increasing age and duration of occupational exposure. Multivariable logistic regression analysis revealed that sex was a significant independent predictor of thyroid abnormalities among radiation workers. Female workers were more likely to experience thyroid abnormalities (β = −0.62, P < 0.05). Conclusion Low-dose ionizing radiation may have a certain impact on the thyroid status of radiation workers, especially for female workers, which requires further attention and research.

ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg^-1）， and high-（10 g·kg^-1）， medium-（5 g·kg^-1）， low-dose （2.5 g·kg^-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.

ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg^-1）， and high-（10 g·kg^-1）， medium-（5 g·kg^-1）， low-dose （2.5 g·kg^-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Objective:To explore the expressions and clinical significances of tripartite motif-containing protein 28 (TRIM28), 3-phosphoinositide-dependent protein kinase-1 (PDK1), and N-cadherin in pancreatic carcinoma.Methods:A total of 72 patients diagnosed with pancreatic carcinoma underwent radical resection in the Department of Hepatobiliary Surgery, Binzhou People′s Hospital from January 2009 to November 2022 were selected, all of which were pathologically diagnosed as pancreatic ductal adenocarcinoma (PDAC). Immunohistochemistry was used to detect the expression of TRIM28, PDK1, and N-cadherin in 72 cases of pancreatic carcinoma and paracancerous tissues, to explore the correlation between the expression of them and the clinicopathological features of pancreatic carcinoma, and to analyze the influence of their expression and clinicopathological characteristics on the prognosis of patients. The count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Spearman method was used for correlation analysis. Kaplan-Meier method was used for survival analysis, and Log-rank test was used to compare the survival rate, and univariate and multivariate Cox regression analysis were used to analyze the risk factors affecting prognosis.Results:The positive rates of TRIM28 (72.22%), PDK1 (65.28%) and N-cadherin (61.11%) in PDAC were significantly higher than those in para-cancerous tissues (26.39%, 33.33%, 34.72%). Moreover, the patients with high expression of the three had the characteristics of low differentiation, late stage, and lymph node metastasis ( P<0.05). TRIM28 was positively correlated with PDK1 and N-cadherin expression in PDAC ( r=0.720, P<0.001; r=0.714, P<0.001), N-cadherin and PDK1 expression in PDAC was also positively correlated ( r=0.854, P<0.001). Kaplan-Meier survival curve showed that the 2-year survival rate of patients with positive TRIM28, PDK1 and N-cadherin (13.46%, 14.89%, 13.64%) was significantly lower than that of patients with negative tumor (50.00%, 40.00%, 39.29%), the differences were statistically significant ( P<0.05). Univariate Cox regression analysis showed that patients with poor differentiation, nerve infiltration and lymph node metastasis, TNM stage Ⅲ+ Ⅳ, TRIM28 positive, PDK1 positive and N-cadherin positive had a significantly increased risk of death within 2 years after surgery ( P<0.05). Multivariate Cox regression analysis showed that poor differentiation, nerve infiltration, TNM stage Ⅲ+ Ⅳ and TRIM28 positive were independent risk factors for poor prognosis of patients with PDAC ( P<0.05). Conclusions:TRIM28, PDK1 and N-cadherin are highly expressed in PDAC, and the expression level is significantly correlated with the malignant degree of PDAC. TRIM28 is an independent risk factor for the prognosis of patients with PDAC.

Objective To compare the effects of CalliSpheres drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)and conventional TACE(c-TACE)on liver fibrosis and liver function in the treatment of primary hepatocellular carcinoma(HCC).Methods A total of 40 patients diagnosed with HCC at Xuzhou Municipal Cancer Hospital of China between October 2020 and October 2022 were enrolled in this study.According to therapeutic scheme,the patients were divided into DEB-TACE group(n=20)and c-TACE group(n=20).The preoperative,and postoperative 5-day and one-month hyaluronidase(HA),type Ⅲ procollagen peptide(P Ⅲ NP),type Ⅳ collagen(CⅣ)and laminin(LN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),albumin(Alb),and prothrombin time(PT)were compared between the two groups.Results The technical success rate was 100％in both groups,and tumor staining completely disappeared immediately after TACE in all patients.The postoperative 5-day levels of HA,LN,P Ⅲ NP,and CⅣ in both groups were remarkably higher than the preoperative ones(P＜0.05).One month after TACE,HA level in the DEB-TACE group was prominently higher than its preoperative value(P＜0.05);HA and LN levels in the c-TACE group were obviously higher than their preoperative values(P＜0.05);and the HA and LN levels in c-TACE group were significantly higher than those in DEB-TACE group(P＜0.05).Five days after TACE,in the DEB-TACE group the AST and PT levels were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);in the c-TACE group the ALT,AST,TBiL and PT were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);the ALT and AST levels in the c-TACE group were strikingly higher than those in the DEB-TACE group while Alb level was strikingly lower than that in the DEB-TACE group(P＜0.05).Conclusion Both CalliSpheres DEB-TACE and c-TACE can aggravate liver fibrosis and cause liver function damage.However,the degree of liver fibrosis and liver function damage caused by CalliSpheres DEB-TACE is less than that caused by c-TACE.(J Intervent Radiol,2024,33:259-263)