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.

ObjectiveTo investigate somatization symptoms in adolescents during frequent earthquakes in Hefei， and to explore their correlation with earthquake experiences. MethodsA cross-sectional survey was used to select 324 adolescents in Hefei as the survey objects. The self-rating scale of somatization symptoms （SSS） and the fatigue intensity scale （FIS） were used to evaluate the somatization symptoms and fatigue degree of middle school students， and multivariate Logistic regression analysis was used to explore the related factors of somatization symptoms and fatigue among middle school students. ResultsA total of 324 adolescents were included， and the overall detection rate of somatization symptoms was 6.5%， and the detection rate of moderate or above fatigue was 20.1%. The results of regression analysis showed that adolescents who were concerned about the earthquake for a longer time （≥1 h） had a higher risk of somatization symptoms （OR=5.430， 95%CI： 1.547-19.058）， and adolescents who received pre-earthquake training had a lower degree of fatigue （OR=0.535， 95%CI： 0.292-0.981） （P<0.05）. ConclusionDuring the frequent earthquakes， adolescents have more somatization symptoms and fatigue. Therefore， it is crucial to enhance health education， reduce the emphasis on event-related reports， and implement earthquake prevention and disaster reduction training to improve the physical and mental health of adolescents.

ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.

A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Renal Fanconi syndrome (FS) is a rare renal manifestation of primary Sjögren's syndrome (pSS). This study aims to analyze the clinical and prognostic characteristics of patients with pSS-associated renal FS (pSS-FS) and provide insights for clinical management.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

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.

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.