Objective: To characterize the sequence polymorphism of HLA-A, -B, and -C loci in the northern Han Chinese population and to evaluate their selection signals and phylogenetic patterns based on long-read sequencing data. Methods: A total of 408 unrelated healthy blood donors were enrolled. Long-read sequencing of HLA-A, -B, and -C loci was performed using the PacBio Sequel II platform. The Ewens-Watterson neutrality test, sliding-window nucleotide diversity (π) and Tajima′s D analyses were conducted, together with genetic distance heatmaps, principal coordinates analysis (PCoA), and maximum likelihood phylogenetic analysis to assess polymorphism distribution, selection signals, and phylogenetic structure across the three loci. Results: The analyzed sequence lengths for the HLA-A, -B, and -C loci were 3 257 bp, 3 794 bp, and 3 831 bp, respectively; the numbers of locus-specific sequence types were 44, 82, and 56, with corresponding locus-specific sequence type diversities of 0.905 2, 0.964 9, and 0.939 8, respectively. The Ewens-Watterson test showed no significant deviation from neutrality (P>0.05). Sliding-window analysis revealed elevated π and Tajima′s D values in exons 2 and 3 as well as in certain intronic regions of HLA-A and HLA-B, whereas HLA-C exhibited relatively lower overall diversity. Genetic distance heatmaps, PCoA, and phylogenetic analysis consistently showed clear clustering in HLA-A and HLA-C, while HLA-B displayed the highest phylogenetic heterogeneity. Conclusion: HLA-A, -B, and -C gene sequences in the northern Chinese Han population exhibit high levels of polymorphism and marked regional heterogeneity. HLA-B shows greater diversity, stronger signals of selection, and more complex phylogenetic structure compared with HLA-A and HLA-C.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

The imaging features of intracranial melanoma are similar to those of other intracranial tumors, and a definite diagnosis often cannot be made solely based on imaging examinations. Although molecular pathology can detect gene mutations and protein markers of intracranial melanoma, its diagnostic specificity is limited due to the cross-expression of markers. Studies have shown that the combined application of imaging and molecular pathology can obviously improve the diagnosis sensitivity and specificity of intracranial melanoma, and by integrating the morphological and molecular characteristics of the melanoma, this combined application can optimize individualized treatment strategies and play important roles in surgical planning, targeted therapy selection, and therapeutic efficacy detection. This article reviews the research progress on the synergistic role of imaging and molecular pathology in the diagnosis and targeted therapy of intracranial melanoma, with the aim of providing a reference for diagnosis and treatment of intracranial melanoma.

Aconitum (Ranunculaceae) has a long-standing history in traditional Chinese medicine (TCM), where it has been widely used to treat conditions such as rheumatoid arthritis (RA), myocardial infarction, and heart failure. However, the potency of Aconitum alkaloids, the primary active components of Aconitum, also confers substantial toxicity. Therefore, assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety. Metabolomics, a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways, provides a comprehensive view of the metabolic state across multiple systems in vivo. This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity, identifying potential sensitive biomarkers, and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM. This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing, aiming to identify more viable methods for characterizing toxic medicinal plants.
Aconitum/metabolism* ; Metabolomics/methods* ; Alkaloids/metabolism* ; Humans ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

As a new type of high-risk packaging container, prefilled syringes are more widely used, and concerns regarding their effectiveness, stability and safety in clinical use have become prominent increasingly. However, the leachable substances from prefilled syringes may cause harm to humans in different degrees. Therefore, this paper reviews the research progress of leachable substances in prefilled syringes, which is not only of great significance for the quality control of prefilled syringe products, but also contributes to the healthy development of the industry.
Syringes ; Drug Packaging ; Quality Control

The imaging features of intracranial melanoma are similar to those of other intracranial tumors, and a definite diagnosis often cannot be made solely based on imaging examinations. Although molecular pathology can detect gene mutations and protein markers of intracranial melanoma, its diagnostic specificity is limited due to the cross-expression of markers. Studies have shown that the combined application of imaging and molecular pathology can obviously improve the diagnosis sensitivity and specificity of intracranial melanoma, and by integrating the morphological and molecular characteristics of the melanoma, this combined application can optimize individualized treatment strategies and play important roles in surgical planning, targeted therapy selection, and therapeutic efficacy detection. This article reviews the research progress on the synergistic role of imaging and molecular pathology in the diagnosis and targeted therapy of intracranial melanoma, with the aim of providing a reference for diagnosis and treatment of intracranial melanoma.

Objective: Epidemiological studies on spinal cord tumors are rare, and studies on primary intramedullary tumors are even rarer. The incidence and survival of patients with primary intramedullary spinal cord tumors have not been well documented. We aimed to study the incidence and survival of patients with primary spinal cord malignant and borderline malignant tumors based on data from the Surveillance, Epidemiology, and End Results (SEER) database and provide information for revealing the epidemiology and exploring the prognosis of patients with primary intramedullary tumors. Methods: Patients in the SEER database with microscopically diagnosed malignant and borderline malignant primary spinal cord tumors from 2000 and 2019 were included in this study. We analyzed the distribution of patients according to the demographic and clinical characteristics. Then, we extracted the incidence rate and 5-year relative survival for the whole cohort and different subgroups of the cohort. Finally, multivariate Cox proportional hazards models were used to analyze the independent prognostic factors associated with overall survival. Results: A total of 5,211 patients with malignant and borderline malignant primary spinal cord tumors were included in this cohort study. Ependymoma, astrocytoma (including oligodendrogliomas and glioblastoma), lymphoma and hemangioblastoma were the most common pathological types. The age-adjusted incidence rates of primary spinal cord ependymoma was 0.18 per 100,000. The incidence rate for females was significantly lower than that for males. The incidence rate was highest in Caucasian. The incidence rate of ependymoma was significantly higher than that of other pathological types. The incidence of astrocytoma was highest among people aged 0–19 years, the incidence of ependymoma was highest among people aged 40–59 years, and the incidence of lymphoma was highest among people aged 60 years or older. The 5-year observed survival and relative survival rates for the whole cohort were 82.80% and 86.00%, respectively. Patients diagnosed with ependymoma had significantly better survival than their counterparts. We also found the impact of surgery and chemotherapy on the prognosis of patients with different tumors varies a lot. Conclusion We conducted a population-based analysis of malignant and borderline malignant primary spinal cord tumors with the aim of revealing the epidemiology and survival of patients with primary intramedullary spinal cord tumors. Despite some shortcomings, this study provides valuable information to help us better understand the epidemiological characteristics of primary intramedullary spinal cord tumors.

Objective: Epidemiological studies on spinal cord tumors are rare, and studies on primary intramedullary tumors are even rarer. The incidence and survival of patients with primary intramedullary spinal cord tumors have not been well documented. We aimed to study the incidence and survival of patients with primary spinal cord malignant and borderline malignant tumors based on data from the Surveillance, Epidemiology, and End Results (SEER) database and provide information for revealing the epidemiology and exploring the prognosis of patients with primary intramedullary tumors. Methods: Patients in the SEER database with microscopically diagnosed malignant and borderline malignant primary spinal cord tumors from 2000 and 2019 were included in this study. We analyzed the distribution of patients according to the demographic and clinical characteristics. Then, we extracted the incidence rate and 5-year relative survival for the whole cohort and different subgroups of the cohort. Finally, multivariate Cox proportional hazards models were used to analyze the independent prognostic factors associated with overall survival. Results: A total of 5,211 patients with malignant and borderline malignant primary spinal cord tumors were included in this cohort study. Ependymoma, astrocytoma (including oligodendrogliomas and glioblastoma), lymphoma and hemangioblastoma were the most common pathological types. The age-adjusted incidence rates of primary spinal cord ependymoma was 0.18 per 100,000. The incidence rate for females was significantly lower than that for males. The incidence rate was highest in Caucasian. The incidence rate of ependymoma was significantly higher than that of other pathological types. The incidence of astrocytoma was highest among people aged 0–19 years, the incidence of ependymoma was highest among people aged 40–59 years, and the incidence of lymphoma was highest among people aged 60 years or older. The 5-year observed survival and relative survival rates for the whole cohort were 82.80% and 86.00%, respectively. Patients diagnosed with ependymoma had significantly better survival than their counterparts. We also found the impact of surgery and chemotherapy on the prognosis of patients with different tumors varies a lot. Conclusion We conducted a population-based analysis of malignant and borderline malignant primary spinal cord tumors with the aim of revealing the epidemiology and survival of patients with primary intramedullary spinal cord tumors. Despite some shortcomings, this study provides valuable information to help us better understand the epidemiological characteristics of primary intramedullary spinal cord tumors.

Malignant tumors pose a serious threat to human health and are one of the main causes of human death worldwide.In order to further improve the therapeutic outcomes of malignant tumors and prolong patients'survival time,clarifying the pathogenesis of malignant tumors and searching for new diagnostic and therapeutic targets become particularly important.It has been found that the occurrence and development of malignant tumors are the results of the interaction between tumor cells and the tumor microenvironment(TME).Versican,encoded by the VCAN gene,is a type of chondroitin sulfate proteoglycan belonging to the exogenous lectin proteoglycan family.It is a major component of the extracellular matrix and plays an important role in embryonic development and inflammatory responses.As an important component of TME,versican is abnormally expressed in various tumor tissues such as renal cell carcinoma,hepatocellular carcinoma,and gastric cancer,and is closely related to the clinical pathological characteristics and prognosis of the patients.It is a potential biomarker for early diagnosis and prognostic evaluation of tumors.Further researches have shown that versican can promote tumor development in a number of ways,such as promoting tumor cell proliferation,invasion and metastasis,inhibiting tumor cell apoptosis,promoting tumor angiogenesis,and inhibiting anti-tumor immune responses.This article reviews the current research status of the expression and biological effects of versican in malignant tumors,aiming to provide reference for subsequent research,clinical diagnosis and treatment of tumors.

Objective: Epidemiological studies on spinal cord tumors are rare, and studies on primary intramedullary tumors are even rarer. The incidence and survival of patients with primary intramedullary spinal cord tumors have not been well documented. We aimed to study the incidence and survival of patients with primary spinal cord malignant and borderline malignant tumors based on data from the Surveillance, Epidemiology, and End Results (SEER) database and provide information for revealing the epidemiology and exploring the prognosis of patients with primary intramedullary tumors. Methods: Patients in the SEER database with microscopically diagnosed malignant and borderline malignant primary spinal cord tumors from 2000 and 2019 were included in this study. We analyzed the distribution of patients according to the demographic and clinical characteristics. Then, we extracted the incidence rate and 5-year relative survival for the whole cohort and different subgroups of the cohort. Finally, multivariate Cox proportional hazards models were used to analyze the independent prognostic factors associated with overall survival. Results: A total of 5,211 patients with malignant and borderline malignant primary spinal cord tumors were included in this cohort study. Ependymoma, astrocytoma (including oligodendrogliomas and glioblastoma), lymphoma and hemangioblastoma were the most common pathological types. The age-adjusted incidence rates of primary spinal cord ependymoma was 0.18 per 100,000. The incidence rate for females was significantly lower than that for males. The incidence rate was highest in Caucasian. The incidence rate of ependymoma was significantly higher than that of other pathological types. The incidence of astrocytoma was highest among people aged 0–19 years, the incidence of ependymoma was highest among people aged 40–59 years, and the incidence of lymphoma was highest among people aged 60 years or older. The 5-year observed survival and relative survival rates for the whole cohort were 82.80% and 86.00%, respectively. Patients diagnosed with ependymoma had significantly better survival than their counterparts. We also found the impact of surgery and chemotherapy on the prognosis of patients with different tumors varies a lot. Conclusion We conducted a population-based analysis of malignant and borderline malignant primary spinal cord tumors with the aim of revealing the epidemiology and survival of patients with primary intramedullary spinal cord tumors. Despite some shortcomings, this study provides valuable information to help us better understand the epidemiological characteristics of primary intramedullary spinal cord tumors.