Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

ObjectiveTo investigate the mechanism by which Jianpi Xiao'ai prescription （JPXAP） inhibits colorectal cancer progression by regulating the inducible nitric oxide synthase-arginase 1 （iNOS-ARG1） metabolic axis and inducing mitochondrial reactive oxygen species （mito-ROS）-mediated mitochondrial structural and functional impairment. MethodsAn arginine metabolism disorder model of human colorectal cancer HCT116 cells was established by combined treatment with recombinant human interferon-γ （IFN-γ， 10 μg·L^-1） and N（ω）-hydroxy-L-arginine （Nor-NOHA， 200 μmol·L^-1） for 24 h， followed by intervention with 5%， 10%， or 20% JPXAP-containing serum. Cell proliferation was assessed using cell counting kit-8 （CCK-8）， 5-ethynyl-2′-deoxyuridine （EdU） staining， and colony formation assays. Cell invasion and migration were evaluated using Transwell chamber and wound healing assays. Mitochondrial membrane potential （MMP） and ROS levels were assessed by JC-1 and MitoSOX staining， respectively. Mitochondrial ultrastructure was observed by transmission electron microscopy （TEM）. The expression of iNOS， ARG1， and mitochondrial dynamics-related proteins， including mitofusin 2 （MFN2） and dynamin-related protein 1 （DRP1）， was analyzed by Western blot and immunofluorescence. The levels of L-arginine， citrulline， and urea were determined by colorimetric methods and enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the blank group， the model group exhibited significantly upregulated iNOS expression， downregulated ARG1 expression， a decreased ARG1/iNOS ratio， reduced L-arginine and urea levels， and increased citrulline levels （P<0.05）. Meanwhile， mito-ROS accumulation was significantly increased， the JC-1 red/green fluorescence ratio was decreased， and mitochondria showed swelling and cristae disruption， indicating that metabolic disorder induced mitochondrial injury. Compared with the model group， all JPXAP-treated groups further decreased the ARG1/iNOS ratio， enhanced nitric oxide （NO） and reactive nitrogen species accumulation， further reduced L-arginine and urea levels， and increased citrulline levels （P<0.01）. EdU-positive rate， colony formation rate， wound healing rate， and Transwell invasion number all decreased significantly with increasing serum concentration （P<0.01）. Mito-ROS levels were further elevated， and the JC-1 red/green ratio further decreased. TEM revealed aggravated mitochondrial swelling and vacuolization. MFN2 expression was downregulated and DRP1 expression was upregulated （P<0.01），in a dose-dependent manner. ConclusionJPXAP further activates NO-mediated oxidative/nitrosative stress under arginine metabolism imbalance， inducing mito-ROS accumulation， MMP collapse， and mitochondrial dynamics imbalance， thereby inhibiting colorectal cancer cell proliferation and migration. These findings reveal an antitumor mechanism of JPXAP based on coordinated targeting of the "metabolism-mitochondria" axis.

Objective This study investigated the diversity of rodent populations and the infection status of Bartonella at three ports along the China-Mongolia border in 2022. Methods Rodents at three Belt and Road ports along the China-Mongolia border, namely Ganqimaodu, Erenhot, and Zhuengadabuqi, were morphologically identified. The Bartonella citrate synthase(gltA)gene was amplified by nested polymerase chain reaction(PCR), and PCR-positive products were sequenced. The resulting sequences were then analyzed for genetic characteristics. Phylogenetic analysis was performed using MEGA 11.0 software using Neighbor-Joining and Maximum-Likelihood method. Results A total of 94 rodents were captured, representing seven species from five families and six genera: Mus musculus, Meriones unguiculatus, Meriones meridianus, Spermophilus dauricus, Allactaga sibirica, Dipus sagitta, and Phodopus roborovskii. Among them, M. unguiculatus was the most abundant species, with 58 rodents, accounting for 61.70% of the total. Overall,11 positive Bartonella pathogen sequences were obtained from the three ports, with a positive detection rate of 11.70%(11/94). The infected rodent species included M. unguiculatus, M. meridianus, and A. sibirica, and two species of Bartonella were detected. Conclusions Rodents at Ganqimaodu, Erenhot, and Zhuengadabuqi ports along the China-Mongolia border were naturally infected with Bartonella. Rodent monitoring and pathogen prevention and control in this area should be strengthened.

Background Large-for-gestational-age (LGA) births are associated with adverse perinatal outcomes and increased risks of offspring obesity, metabolic syndrome, and cardiovascular diseases later in life. Beyond traditional risk factors, exposure to environmental factors, especially fine particulate matter (PM_2.5), before and during pregnancy may contribute to excessive fetal growth; however, the roles of specific chemical constituents and critical exposure windows remain unclear. Objective To examine the associations between maternal exposures to PM_2.5 and its chemical constituents before and during pregnancy and the risk of delivering LGA infants. Methods Singleton pregnancies from the National Free Preconception Health Examination Project between 2010 and 2014 were included. Individual exposures to PM_2.5 and its constituents were estimated for preconception and pregnancy windows using geocoded residential addresses. The associations of single and mixed exposures with LGA risk were analyzed using generalized linear models (GLMs) and qg-computation. Results Exposures to PM_2.5 and its major chemical constituents were significantly associated with an increased LGA risk, with differences in effect magnitude across components. Secondary inorganic aerosols showed the strongest associations. For full-pregnancy exposure, nitrate (OR=1.330, 95%CI: 1.313, 1.347), ammonium (OR=1.279, 95%CI: 1.263, 1.295), and sulfate (OR=1.242, 95%CI: 1.227, 1.257) had larger effects on LGA risk than black carbon and organic matter. Analysis by exposure window indicated that the month preceding conception and the third trimester of pregnancy were critical exposure windows for susceptibility, while the strongest effect was observed for full-pregnancy exposure, suggesting a cumulative effect over time. Mixed exposure analysis further showed that nitrate and sulfate consistently accounted for the main positive contributions across different time windows. Conclusion Maternal exposures to PM_2.5 and its chemical components before and during pregnancy are associated with an elevated LGA risk. Nitrate and sulfate show consistent and strong associations across pregnancy stages, underscoring the importance of component composition and exposure timing in fetal overgrowth.

Objective: To examine the association between health behaviors and depressive symptoms among junior and senior high school students, so as to provide evidence for combined behavioral interventions targeting adolescent mental health. Methods: From September to November 2023, a stratified cluster random sampling method was used to recruit 104 834 junior and senior high school students from all 13 prefecture level cities (124 districts/counties) in Heilongjiang Province, China. Multivariable Logistic regression models, as well as multiplicative and additive interaction analyses were employed to analyze the associations between health behaviors and depressive symptoms, and Chi-square tests for trend were conducted to explore ,the changing tendency in the risk of depressive symptoms with increasing numbers of health behaviors among junior and senior high school students. Results: Healthy diet ( OR =0.66, 95% CI =0.63-0.68), healthy physical activity ( OR =0.47, 95% CI =0.45-0.49), healthy outdoor activity ( OR =0.55, 95% CI =0.52-0.57), healthy sleep ( OR =0.72, 95% CI =0.69-0.75), and healthy screen use ( OR =0.79, 95% CI =0.76-0.82) were independently associated with lower rates of depressive symptoms (all P <0.01). The risk of depressive symptoms decreased progressively with an increasing cumulative number of health behaviors ( χ 2 trend =996.73, P <0.01). Except for the interaction between healthy diet and healthy sleep, significant additive interactions were observed among the remaining health behaviors( RERI =0.07-0.23,all P <0.05). The probability of depressive symptoms was lower among girls with 2-3 healthy behaviors than among boys ( Z =2.51, 2.65), lower among urban students with 2-3 healthy behaviors than among suburban county students ( Z =-2.36, -2.04), and lower among senior high school students with 2-4 healthy behaviors than among junior high school students ( Z =2.17, 2.10, 2.04) (all P <0.05). Conclusions Health behaviors are significantly associated with depressive symptoms among junior and senior high school students. The probability of depressive symptoms is lower among girls, urban students, and senior high school students who engage in multiple healthy behaviors. Implementing combined interventions targeting multiple health behaviors in these populations may yield greater benefits.

ObjectiveMethylthioadenosine phosphorylase (MTAP) is found to be frequently deleted in malignant cancers, but the role of MTAP underlying metastasis and stemness of liver cancer remains far from clear. 5-fluorouracil (5-Fu) is clinically used in treating advanced liver cancer, however, chemoresistance is one of the major barriers impeding its efficacy. Liver cancer stem cells are considered to be the reservoir for tumor progression and chemoresistance. This study aims to explore the role of MTAP in regulating stemness and chemoresistance of 5-Fu in liver cancer. It is designed to elucidate the molecular mechanisms underlying MTAP-manipulated stemness. How MTAP influences metastasis and chemoresistance against 5-Fu in liver cancer is also elaborated. MethodsThe correlation of MTAP expression with stemness marker CD133 was evaluated by flow cytometry. Colony formation assays were conducted to analyze the tumorigenic ability. Western blot assays were applied to delineate the molecular mechanisms underlying MTAP-regulated stemness. Trans-well assays were conducted to analyze the metastatic potential of liver cancer cells.In vivo experiments were performed using subcutaneous xenograft and lung metastasis model on nude mice. Tumor size and weight were analyzed upon 5-Fu treatment. Metastatic nodules on lungs were evaluated. Immunohistochemical and TUNNEL assays were performed on slides obtained from tumor tissues. ResultsMTAP overexpression inhibited expression of CD133 and colony formation, which is further ablated by MTAP inhibitor. MTAP deprivation augmented stemness and colony formation, which is reversed by protein arginine methyltransferase 5 (PRMT5) overexpression but not its catalytically inactive counterparts. Critically, SRY-box transcription factor 2 (SOX2) was found to be a downstream regulator of MTAP/PRMT5, leading to stemness of liver cancer cells. MTAP overexpression suppressed SOX2 expression, while MTAP inhibition augmented expression of SOX2. Critically, MTAP overexpression inhibited migration and invasion of liver cancer cells. In vivo experiments in animal model found that MTAP deprivation promotes tumor growth and metastatic nodules of liver cancer. Additionally, MTAP overexpression inhibits tumor growth. Moreover, MTAP deprivation contributes to chemoresistance shown by increased tumor size and weight treated by 5-Fu. In contrast, MTAP overexpression led to further decline in tumor size and weight elicited by 5-Fu treatment. Accordingly, SOX2 was inhibited in tumor tissues after MTAP overexpression. Marker of proliferation Ki67 (Ki67) expression was dampened while apoptosis was found in MTAP-overexpressed tumor tissues. ConclusionIn this study, plethora of experimental studies collectively demonstrated that MTAP deprivation enhances stemness of liver cancer by regulating SOX2, exerting anti-cancer and chemoresistant role against 5-Fu in liver cancer. It is also worth noting that MTAP inhibition promoted metastasis of liver cancer. MTAP overexpression augmented tumor shrinking elicited by 5-Fu and SOX2 was involved in this process. These results concluded that MTAP/PRMT5/SOX2 signaling axis was involved in regulating stemness and chemoresistance of liver cancer. These findings help to exploit novel therapies by targeting stemness in MTAP-depleted liver cancer. It shed novel light on unveiling MTAP-regulated stemness in antagonizing 5-Fu treatment in liver cancer. It also adds mounting evidence to the theoretical basis for accomplishing personalized chemotherapy of liver cancer patients by targeting MTAP or its downstream PRMT5/SOX2.

Objective To investigate prevalence and immunological properties of Helicobacter pylori (Hp) infection among chronic gastritis population in Wuhan. Methods A total of 1 866 patients with chronic gastritis in Wuhan were selected from May 2021 to December 2023, and Hp antibody and typing in serum were detected by immunoblotting to analyse the infection rate and typing of patients of different genders and age groups, as well as the correlation between Hp infection and the severity of chronic gastritis. Western blotting technique was utilized to detect the Hp antibodies and typing. The infection rates and subtypes were recorded in patients of different genders and ages. Then the correlation between Hp infection and the severity of chronic gastritis were discussed. Results The overall detection rate of Hp infection was 65.38% (1 220/1 866) in 1866 patients, and the prevalence rate of type I infection was higher than that of type II infection [61.31% (748/1 220) vs 38.69% (472/1 220), P<0.05]. No statistical difference was reported in overall infection rate in terms of gender (P>0.05). In terms of gender, the rate of type I infection was higher than that of type II infection [70.08% (431/615) vs 29.92% (184/615), P<0.05], whereas the prevalence of the two types of infections demonstrated no statistical difference in female patients (P>0.05). In terms of age, the prevalence of Hp infection in patients increased with age (2=64.687, P=0.000). The infection rate of type I was higher than type II in the age groups of below 18, 31-40, 41-50 and 51-60 years old (P<0.05), and infection rates of type I and type II yielded no statistical difference in the age groups of 18-30 and ≥60 years old (P>0.05). With the aggravation of chronic gastritis, the infection rate and percentage of type I infections increased, and the percentage of type I infections was higher than that of type II infections (P<0.05). Conclusion Patients with chronic gastritis in Wuhan suffer a high prevalence rate of Hp infection, and the rate of Hp infection increases with the age of the patients, is positively correlated with the severity of the disease, and presents certain typological features.

Sleep， skin， and health are closely interconnected. Clinically， insomnia has a high incidence and is often accompanied by or secondary to skin aging. The two conditions exhibit "different diseases with the same syndrome"， significantly affecting the physical and mental health of the Chinese population. Preventing and treating skin aging by improving insomnia is an important strategy， with the principle of "treating different diseases with the same approach" serving as a crucial therapeutic guideline. However， effective clinical prevention and treatment methods for both conditions remain lacking. Traditional Chinese medicine （TCM） has a profound theoretical foundation and notable efficacy in the concurrent treatment of insomnia and skin aging， yet there are few reports on the etiology， pathogenesis， therapeutic principles， and treatment methods of their shared treatment， warranting further exploration. Based on holistic view and syndrome differentiation and treatment in TCM， this study systematically investigates the theoretical origins of the shared manifestations of insomnia and skin aging from multiple dimensions， including etiology， pathological location， pathogenesis， disease nature， and prevention and treatment strategies. As early as Huangdi's Internal Classic （Huangdi Neijing）， it was recognized that mental clarity during the day， sound sleep at night， and firm， healthy skin are key indicators of external health， whereas daytime lethargy， poor sleep quality， and dry， withered skin are prominent signs of aging. Maintaining mental clarity during the day and restful sleep at night is essential for skin integrity and healthy aging. Later medical scholars proposed that the common etiology of insomnia and skin aging lies in "internal-external interactions"， with the pathological location involving "the five organ systems". The primary pathogenesis includes "deficiency， fire， stagnation， phlegm， and blood stasis"， while the disease nature is often characterized by "a combination of deficiency and excess". Treatment should be guided by syndrome differentiation， following the principle of balancing Yin and Yang. This theoretical exploration enriches and advances TCM understanding of disease onset and prevention， providing theoretical guidance for the clinical prevention and treatment of insomnia-associated skin aging and contributing to the realization of the "Healthy China" initiative.