This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.
Humans ; Cerebral Small Vessel Diseases/pathology* ; Inflammation/pathology* ; Cerebral Amyloid Angiopathy/pathology* ; Vasculitis, Central Nervous System/pathology* ; Vasculitis/pathology*

Objective : To explore the correlation between the clinical, pathological, genetic features, prognosis, and tumor lymph node metastasis in patients with stage ⅠA-Ⅲ B lung invasive non-mucinous adenocarcinoma(INMA). Methods: A retrospective analysis was conducted on 67 eligible patients with INMA. Clinical data, histopathological assessments, and genetic testing were collected. Disease progression-free survival(PFS) was the primary endpoint through follow-up. The chi-square test or Fisher's exact test was used to analyse the correlation between tumour lymph node metastasis and clinicopathological and genetic characteristics. The Cox proportional hazards regression model and Kaplan-Meier method were used to analyse the impact of tumour lymph node metastasis on prognosis. Results: A total of 67 patients were included, aged 46-77 years, with a median age of 61 years. Age, gender, and smoking history were not significantly associated with tumor lymph node metastasis. Larger tumor diameter, tumor progression, and receiving postoperative adjuvant treatment were associated with tumour lymph node metastasis(P<0.05). Poorer differentiated tumors according to International Association for the Study of Lung Cancer(IASLC) grading system was more likely to have lymph node metastasis(P=0.043). There was no significant difference in the types of driver gene mutations and lymph node metastasis. However,EGFRmutations were more common in patients without lymph node metastasis, while co-mutations were more common in patients with lymph node metastasis. Lymph node metastasis was significantly associated with PFS. Patients without lymph node metastasis had a significantly better PFS compared to those with lymph node metastasis(P=0.002). Under different treatment conditions, patients without lymph node metastasis exhibited a significant advantage in PFS when untreated. While treatment showed a trend toward improved PFS, the difference did not reach statistical significance. Additionally, no significant differences in PFS were observed between patients with or without lymph node metastasis following chemotherapy or targeted therapy. Conclusion Lymph node metastasis in INMA patients is related to tumor size, progression status, and gene co-mutations, and is a key prognostic indicator affecting PFS.

Objective: To investigate the correlations among clinicopathological features, histopathological growth patterns and prognosis of extrapulmonary multiple metastatic(stage ⅣB) pulmonary adenocarcinoma with epidermal growth factor receptor(EGFR) mutations. Methods : A total of 488 eligible patients with adenocarcinoma of stage ⅣB. Clinicopathological data,EGFRgene mutation subtypes, metastatic sites, histopathological growth patterns and survival information were collected. The chi-square test(χ2test) and Fisher's exact probability method were used to detect the correlation between the metastasis status and various clinical characteristics; the Kaplan-Meier method was used to conduct survival analysis on the median Progression-Free Survival(PFS) under different clinical characteristics. Cox univariate and multivariate regression analyses were conducted to evaluate the impact of various clinical characteristics on prognosis. Results : The metastatic patterns of stage ⅣB pulmonary adenocarcinoma withEGFRmutations was correlated with histopathological growth patterns(P<0.05). In the group with multiple metastases in a single organ, the proportion of micropapillary type in the group with multiple metastases in a single organ was higher than that in the group with multiple-organ metastases(51.1%vs41.1%), while the proportion of solid type in the group with multiple-organ metastases was higher than that in the group with multiple metastases in a single organ(23.8%vs14.2%). Multiple brain or multiple bone metastases were correlated with histopathological growth patterns and tumor differentiation degree. Compared with the multiple bone metastases group, the proportion of acinar type decreases in the multiple brain metastasis group, while the proportion of micropapillary type increased. Moreover, the proportion of poorly differentiated tumors increased significantly(P<0.05). Compared with multiple bone metastases, the proportion of poorly differentiated tumors significantly increases in the group with multiple brain metastases. The median progression-free survival(PFS) of patients with a predominant solid growth pattern was shorter than that of patients with other growth patterns(12.7 monthsvs17.8 months,P<0.05). The PFS of patients in the poorly differentiated group was worse than that in the moderately differentiated group(15.6 monthsvs17.8 months,P<0.05). There were significant differences in PFS among patients with common sensitive mutations and rare mutationsEGFR(17.3 monthsvs10.2 months,P<0.01). Cox proportional hazards regression model suggested that solid growth pattern, poor differentiation and rare single gene mutation were adverse prognostic factors. Conclusion In stage ⅣB pulmonary adenocarcinoma patients withEGFRmutations, both the metastatic patterns and metastatic sites are significantly correlated with the histopathological growth patterns of tumors. Moreover, theEGFRmutation subtypes as well as the histopathological growth patterns and differentiation degree of tumors significantly affect the prognosis of patients.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Objective:To investigate the potential causal relationships between gut microbiota composition and the risk of developing various subtypes of breast cancer by using bidirectional two-sample Mendelian randomization(MR).Methods:The research utilized genome-wide association studies(GWAS) data on gut microbiota from the MiBioGen database and GWAS data on breast cancer from the Breast Cancer Association Consortium (BCAC). In this MR study, inverse variance weighted (IVW), weighted median, MR Egger, and MR-PRESSO methods were used. Additionally, reverse MR and stratified analyses were conducted to assess reverse causality and the impact on different subtypes of breast cancer.Results:Adlercreutzia (IVW OR=0.92, 95% CI: 0.87-0.98, P=0.01) and Parabacteroides (IVW OR=0.87, 95% CI: 0.79-0.96, P=0.007) exhibited a statistically significant protective effect on breast cancer. Conversely, Sellimonas (IVW OR=1.05, 95% CI: 1.01-1.09, P=0.01) was significantly associated with an increased risk of breast cancer. Desulfovibrio (IVW OR=0.94, 95% CI: 0.88-1.00, P=0.04) and Ruminococcaceae (UCG013) (IVW OR=0.92, 95% CI: 0.86-0.99, P=0.03) presented suggestive protective effects against breast cancer. Furthermore, stratified analysis revealed that the protective effect of Adlercreutzia against breast cancer persisted in the estrogen receptor(ER)-positive subtypes, while Desulfovibrio persisted in the ER-negative subtypes. Sellimonas was causally associated with the risk of ER-positive subtypes. CACNA1S was identified as the functional gene of Adlercreutzia, and associated with favorable prognosis in breast cancer, while ERBB4 was identified as the functional gene of Sellimonas and associated with poor prognosis in breast cancer. Conclusions:This study identifies the causal relationships between gut microbiota and breast cancer, suggesting a novel target for early clinical intervention and treatment, with potential implications for future functional analysis.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Objective:To investigate the potential causal relationships between gut microbiota composition and the risk of developing various subtypes of breast cancer by using bidirectional two-sample Mendelian randomization(MR).Methods:The research utilized genome-wide association studies(GWAS) data on gut microbiota from the MiBioGen database and GWAS data on breast cancer from the Breast Cancer Association Consortium (BCAC). In this MR study, inverse variance weighted (IVW), weighted median, MR Egger, and MR-PRESSO methods were used. Additionally, reverse MR and stratified analyses were conducted to assess reverse causality and the impact on different subtypes of breast cancer.Results:Adlercreutzia (IVW OR=0.92, 95% CI: 0.87-0.98, P=0.01) and Parabacteroides (IVW OR=0.87, 95% CI: 0.79-0.96, P=0.007) exhibited a statistically significant protective effect on breast cancer. Conversely, Sellimonas (IVW OR=1.05, 95% CI: 1.01-1.09, P=0.01) was significantly associated with an increased risk of breast cancer. Desulfovibrio (IVW OR=0.94, 95% CI: 0.88-1.00, P=0.04) and Ruminococcaceae (UCG013) (IVW OR=0.92, 95% CI: 0.86-0.99, P=0.03) presented suggestive protective effects against breast cancer. Furthermore, stratified analysis revealed that the protective effect of Adlercreutzia against breast cancer persisted in the estrogen receptor(ER)-positive subtypes, while Desulfovibrio persisted in the ER-negative subtypes. Sellimonas was causally associated with the risk of ER-positive subtypes. CACNA1S was identified as the functional gene of Adlercreutzia, and associated with favorable prognosis in breast cancer, while ERBB4 was identified as the functional gene of Sellimonas and associated with poor prognosis in breast cancer. Conclusions:This study identifies the causal relationships between gut microbiota and breast cancer, suggesting a novel target for early clinical intervention and treatment, with potential implications for future functional analysis.

Objective To compare the effects of different axillary lymph node surgical procedures on complications following immediate two-stage breast reconstruction after mastectomy.Methods A retrospective analysis was performed on 232 patients who underwent mas-tectomy with immediate two-stage breast reconstruction in the Department of Breast Surgery at the First Hospital of China Medical Uni-versity between January 2018 and December 2021.Patients were divided into two groups based on the type of axillary lymph node surgery performed:the sentinel lymph node biopsy group(SLNB group,n=84)and the axillary lymph node dissection group(ALND group,n=148).We compared baseline characteristics,surgical procedures,and postoperative complications between the two groups.Results The ALND group had a higher prevalence of advanced T and N stages,received neoadjuvant chemotherapy more frequently,and underwent chemotherapy and radiotherapy at a higher rate compared to the SLNB group.Additionally,the ALND group experienced greater drainage volume and a significantly higher complication rate(all P<0.05).Postoperative infection was the most common complication observed in the ALND group.Importantly,no significant differences were found in long-term outcomes(local/regional recurrence,distant metastasis,and disease-free survival)between the two groups(all P>0.05).Conclusion In patients undergoing immediate two-stage breast recon-struction after mastectomy,axillary lymph node dissection is associated with a higher rate of reconstruction complications compared to sentinel lymph node biopsy.