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.

Hepatitis B virus （HBV） infection is one of the major global health problems， and it can lead to the development of liver cirrhosis and hepatocellular carcinoma. Due to the strict species specificity of HBV infection， no animal model has yet been established to fully support the complete life cycle of HBV infection and accurately reflect host immune responses and pathogenesis. Current animal models used for HBV research include various hosts such as chimpanzees， tree shrews， and mice， as well as surrogate models based on related hepatotropic viruses. Although these models have contributed significantly to the research on HBV replication， immune response， and antiviral drug evaluation， they still have certain limitations such as ethical concerns， low infection efficiency， high costs， and a lack of persistent infection. In recent years， the development of novel strategies， such as humanized mouse models with reconstituted human liver and immune systems， transgenic models， and viral vector-mediated infection systems， has greatly promoted the research on HBV biology. In the future， with the integration of emerging technologies including gene editing， tissue engineering， and multi-system reconstruction， it is possible to establish HBV infection models that can more closely mimic human pathophysiology， thereby laying a robust foundation for understanding virus-host interactions， exploring the pathways for viral clearance， and developing radical treatment strategies.

ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis（RA） and traditional Chinese medicine（TCM） syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide， in which general information such as name， gender， age， height， body weight， and course of disease were collected by completing a questionnaire； patients were classified into eight types of syndrome according to the information of their four examinations，i.e. wind-dampness obstruction syndrome， cold-dampness obstruction syndrome， dampness-heat obstruction syndrome， phlegm-stasis obstruction syndrome， stasis-blood obstructing collateral syndrome， qi-blood deficiency syndrome， liver-kidney insufficiency syndrome， and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events， they were divided into the occurrence group and the non-occurrence group， and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events， and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included， including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height， gender， insomnia， appetite， white blood cell（WBC）， hemoglobin（HGB）， platelets（PLT）， rheumatoid factor（RF）， anti-cyclic peptide containing citrulline（CCP）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， γ-glutamyl transpeptidase（GGT）， urea creatinine（CREA）， and glucose（GLU）（P＞0.05）. The TCM syndromes between groups showed significant statistic differences（P＜0.05）. Patients in occurrence group had longer disease duration， heavier body weight， and older age； more severe conditions such as disease activity（DAS-28）， number of painful joints（TJC）， number of swollen joints（SJC）， health questionnaire scores（HAQ）， visual analog scores（VAS）， restlessness， and fatigue； higher blood sedimentation rate（ESR）， low-density lipoprotein（LDL-C）， triglyceride（TG）， total cholesterol（TC）， D-Dimer， and lower high-density lipoprotein（HDL-C）（P＜0.05）. The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome［OR=5.937， 95%CI （4.434， 7.949）， P＜0.001］. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes， and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.

Objective:To validate the accuracy of three-dimensional anatomical models reconstructed from cone beam CT (CBCT) using micro-CT as the gold standard, and to evaluate the feasibility of performing anatomical analyses on such models.Methods:A total of 13 isolated deciduous teeth with intact roots were collected, including 5 anterior teeth and 8 molars, with a total of 34 root canals. The teeth were extracted from children aged 3-9 years who visited Peking University Hospital of Stomatology from January 2019 to April 2022 due to trauma or periapical disease, and were then scanned by micro-CT (with a voxel size of 0.018 mm) and CBCT (with a voxel size of 0.125 mm), respectively. Using a threshold-based semi-automated region segmentation method, anatomical models of these isolated teeth were reconstructed from the two CTs. Subsequently, the two CT reconstructed models were registered based on the iterative closest point algorithm, followed by deviation analysis. The key anatomical parameters were measured on the micro-CT and CBCT models, respectively, and the differences were calculated.Results:The CBCT reconstruction models were relatively accurate in the hard tissue morphology, and 97.1% (33/34) of the root canals were identified accurately. When it comes to the deviation analysis, the average distance between the matched points on the CBCT reconstruction models and the micro-CT models was (0.01±0.03) mm for the hard tissue, and (0.00±0.03) mm for the pulp chambers and canals, which did not affect clinical observation. The hard tissue and root canal length of CBCT models were both smaller than those of micro-CT models ( P<0.05), with a 95% limits of agreement of (-0.70, 0.14) mm for the hard tissue, and a 95% limits of agreement of (-1.93, 1.00) mm for the pulp chambers and canals. The impact of these differences on clinical operations was all within the acceptable range. Conclusions:Using micro-CT as a validate standard, CBCT with a voxel size of 0.125 mm was proved to be an effective tool for the reconstruction of deciduous teeth. Therefore, the reconstructed models were appropriate for studying deciduous teeth anatomy.

Large language models (LLMs), represented by ChatGPT, have garnered significant attention due to their powerful capabilities in understanding and generating human language. Research on the application of LLMs across various medical tasks has shown a vigorous development trend. This review aims to outline the development and clinical applications of LLMs, with a focus on the primary tasks of medical intelligent assistants, including their associated opportunities and challenges. At the technical level, we provide a detailed explanation of the architecture and training processes of existing medical LLMs, and summarize the general technical steps for adapting large models to the healthcare domain. At the application level, we introduce the main tasks of medical intelligent assistants from both healthcare provider- and patient-oriented perspectives, andcompare the performance of different LLMs across various medical tasks to illustrate their unique advantages and limitations in medical applications.

Systemic lupus erythematosus （SLE） may lead to secondary gynecological and obstetric disorders such as decreased ovarian reserve function， menstrual abnormalities， and adverse pregnancy outcomes. Based on "bi （痹） of both body and viscera" theory， this paper proposed that the core mechanism of SLE secondary gynecological and obstetric diseases lies in the mutual transformation between "body bi" and "viscera bi"， which together affect the uterus. Physiologically， uterus forms an internal-external network with the body and viscera through the meridians and blood vessels. Pathologically， when the healthy qi is deficient， nourishment of the body and viscera is impaired； when toxins and stasis accumulate， pathogenic factors disturb the uterus through the chong （冲） and ren （任） meri-dians. The resulting obstruction in the uterus can， in turn， manifest externally and aggravate damage to the body and viscera. Therefore， the pathogenesis of SLE secondary gynecological and obstetric diseases follows a dynamic trajectory of "body bi first， body bi affecting viscera， and then bi of both body and viscera". In treatment， the principle of harmonizing and balancing the healthy qi is emphasized. The main approach is to regulate the viscera， stabilize the body， and nourish the uterus， with the coordination of nourishing the viscera through the body， thereby achieving simultaneous treatment of both body and viscera. This highlights the guiding significance of the "bi of both body and viscera" theory in preventing and treating SLE secondary gynecological and obstetric diseases.

Objective:To investigate the expression of keratin 1 (KRT1) and sialyl-Tn antigen (sTn) in cervical squamous cell carcinoma and its possible mechanism.Methods:Six cervical squamous cell carcinoma specimens were collected at the First Affiliated Hospital of Soochow University, Suzhou, China from 2022 to 2023. Spatial transcriptomics analysis was performed on the paraffin sections of 6 patients to analyze the transcriptomes of invasive squamous cell carcinoma and adjacent normal cervical squamous epithelium. The differential gene KRT1 was selected. Kaplan-Meier survival analysis was used to examine the prognostic value of KRT1 in cervical squamous cell carcinoma patients using the TCGA database. The possible downstream molecule sTn was identified according to literature research. Immunohistochemistry was carried out to investigate the expression of KRT1 and sTn proteins in the primary tumor and metastases of cervical squamous cell carcinoma (40 cases with pelvic lymph node metastasis and 30 cases without). Spearman correlation analysis was conducted to analyze the correlation of their expression.Results:The spatial transcriptomic results of the 6 specimens indicated that the level of KRT1 mRNA significantly decreased in cervical squamous cell carcinoma (compared with that in adjacent normal cervical squamous epithelium), while Kaplan-Meier survival analysis revealed that cervical squamous cell carcinoma patients with low KRT1 mRNA levels (versus high) had a worse prognosis. Immunohistochemistry proved that KRT1 expression was significantly lower in cervical squamous cell carcinoma than in adjacent normal squamous epithelium ( P<0.05), but sTn showed the opposite change (increased in carcinoma, P<0.05). The expression changes of KRT1 and sTn were inversely correlated ( r=-0.217, P<0.05). In addition, the expression levels of KRT1 and sTn in lymph node metastases were not significantly different from those in primary tumors. Conclusions:The decreased expression of KRT1 in primary cervical squamous cell carcinoma and lymph node metastasis may promote tumor cell proliferation and inhibit apoptosis by upregulating sTn, contributing to the poor prognosis of advanced cervical squamous cell carcinoma.

Objective To evaluate the clinical efficacy and safety of the daratumumab-based regimens,including daratumumab,dexamethasone,and lenalidomide(DRd),as well as daratumumab,dexamethasone,and bortezomib(DVd),in the treatment of patients with relapsed or refractory multiple myeloma(RRMM)at our center.Methods Eighty patients with RRMM were assigned to either the DRd group(42 cases)or the DVd group(38 cases)based on their treatment regimens.Both groups received a baseline treatment of daratumumab combined with dexamethasone(Dd regimen).In the DVd group,1.3 mg/m2 of bortezomib was administered subcutaneously on days 1,4,8,and 11 of each cycle,followed by a 10 day drug-free interval(days 12～21),repeated every 3 weeks until disease progression.In the DRd group,25 mg of lenalidomide was orally administered daily from day 1 to day 21 of each cycle,in addition to the Dd regimen,continuing until disease progression.The two groups were compared in terms of laboratory parameters,tumor markers,clinical efficacy,safety profiles,and long-term prognostic outcomes.Results After treatment,the overall response rate(ORR)of the DRd group and the DVd group was 78.57%(33 out of 42 cases)and 52.63%(20 out of 38 cases),respectively.The serum creatinine(SCr)levels were(92.54±14.33)and(102.07±15.41)μmol/L,respectively;the M protein contents were(19.62±2.04)and(21.08±2.23)g/L,respectively;the β2-microglobulin(β2-MG)levels were(3.49±1.12)and(4.16±1.25)mg/L,respectively;and the progression-free survival rates were 42.86%(18 out of 42 cases)and 26.32%(10 out of 38 cases),respectively.All these indicators showed statistically significant differences between the DRd group and the DVd group(all P<0.05).The incidence rates of adverse reactions in the observation group and the control group were 14.29%(6 out of 42 cases)and 13.16%(5 out of 38 cases),respectively,and the difference was not statistically significant(P>0.05).Conclusion The DRd regimen demonstrates superior efficacy compared to the DVd regimen in treating patients with RRMM,leading to improved patient prognosis with a favorable safety profile.

Objective:To validate the accuracy of three-dimensional anatomical models reconstructed from cone beam CT (CBCT) using micro-CT as the gold standard, and to evaluate the feasibility of performing anatomical analyses on such models.Methods:A total of 13 isolated deciduous teeth with intact roots were collected, including 5 anterior teeth and 8 molars, with a total of 34 root canals. The teeth were extracted from children aged 3-9 years who visited Peking University Hospital of Stomatology from January 2019 to April 2022 due to trauma or periapical disease, and were then scanned by micro-CT (with a voxel size of 0.018 mm) and CBCT (with a voxel size of 0.125 mm), respectively. Using a threshold-based semi-automated region segmentation method, anatomical models of these isolated teeth were reconstructed from the two CTs. Subsequently, the two CT reconstructed models were registered based on the iterative closest point algorithm, followed by deviation analysis. The key anatomical parameters were measured on the micro-CT and CBCT models, respectively, and the differences were calculated.Results:The CBCT reconstruction models were relatively accurate in the hard tissue morphology, and 97.1% (33/34) of the root canals were identified accurately. When it comes to the deviation analysis, the average distance between the matched points on the CBCT reconstruction models and the micro-CT models was (0.01±0.03) mm for the hard tissue, and (0.00±0.03) mm for the pulp chambers and canals, which did not affect clinical observation. The hard tissue and root canal length of CBCT models were both smaller than those of micro-CT models ( P<0.05), with a 95% limits of agreement of (-0.70, 0.14) mm for the hard tissue, and a 95% limits of agreement of (-1.93, 1.00) mm for the pulp chambers and canals. The impact of these differences on clinical operations was all within the acceptable range. Conclusions:Using micro-CT as a validate standard, CBCT with a voxel size of 0.125 mm was proved to be an effective tool for the reconstruction of deciduous teeth. Therefore, the reconstructed models were appropriate for studying deciduous teeth anatomy.

Objective To evaluate the clinical efficacy and safety of the daratumumab-based regimens,including daratumumab,dexamethasone,and lenalidomide(DRd),as well as daratumumab,dexamethasone,and bortezomib(DVd),in the treatment of patients with relapsed or refractory multiple myeloma(RRMM)at our center.Methods Eighty patients with RRMM were assigned to either the DRd group(42 cases)or the DVd group(38 cases)based on their treatment regimens.Both groups received a baseline treatment of daratumumab combined with dexamethasone(Dd regimen).In the DVd group,1.3 mg/m2 of bortezomib was administered subcutaneously on days 1,4,8,and 11 of each cycle,followed by a 10 day drug-free interval(days 12～21),repeated every 3 weeks until disease progression.In the DRd group,25 mg of lenalidomide was orally administered daily from day 1 to day 21 of each cycle,in addition to the Dd regimen,continuing until disease progression.The two groups were compared in terms of laboratory parameters,tumor markers,clinical efficacy,safety profiles,and long-term prognostic outcomes.Results After treatment,the overall response rate(ORR)of the DRd group and the DVd group was 78.57%(33 out of 42 cases)and 52.63%(20 out of 38 cases),respectively.The serum creatinine(SCr)levels were(92.54±14.33)and(102.07±15.41)μmol/L,respectively;the M protein contents were(19.62±2.04)and(21.08±2.23)g/L,respectively;the β2-microglobulin(β2-MG)levels were(3.49±1.12)and(4.16±1.25)mg/L,respectively;and the progression-free survival rates were 42.86%(18 out of 42 cases)and 26.32%(10 out of 38 cases),respectively.All these indicators showed statistically significant differences between the DRd group and the DVd group(all P<0.05).The incidence rates of adverse reactions in the observation group and the control group were 14.29%(6 out of 42 cases)and 13.16%(5 out of 38 cases),respectively,and the difference was not statistically significant(P>0.05).Conclusion The DRd regimen demonstrates superior efficacy compared to the DVd regimen in treating patients with RRMM,leading to improved patient prognosis with a favorable safety profile.