OBJECTIVE: To analyze the MYH9 gene sequence of a patient with hereditary thrombocytopenia and diffuse large B-cell lymphoma and his family members, and to explore the relationship between MYH9 gene and tumors. METHODS: Peripheral blood samples were collected from the patients and their family members for complete blood count analysis. The platelet morphology was observed under microscope. The MYH9 gene sequence was analyzed by Whole Exon Sequencing and Sanger Sequencing. RESULTS: The mutation site c.279C>A:p.(Asn93Lys) in exon 2 of the MYH9 gene were found in patient and his family members, both presenting as thrombocytopenia. The platelet count was significantly increased after the administration of Avatrombopag. CONCLUSION A novel mutation of MYH9 was found in this study, and the case was sensitive to Avatrombopag, by exploring the relationship between the MYH9 gene and tumors, suggesting that the MYH9 gene may be associated with the development of diffuse large B-cell lymphoma.
Humans ; Myosin Heavy Chains/genetics* ; Thrombocytopenia/genetics* ; Mutation ; Male ; Lymphoma, Non-Hodgkin/genetics* ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Molecular Motor Proteins/genetics* ; Pedigree

Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide. Among its histological subtypes, non-small cell lung cancer (NSCLC) accounts for the majority of cases, representing the predominant pathological type. Notably, in the elderly population, NSCLC continues to be a major contributor to cancer-related deaths. With the global ageing population, immunosenescence has emerged as a key factor influencing the occurrence, progression, and the efficacy of immunotherapy of NSCLC. Immunosenescence refers to the age-related decline in immune system function, which manifests as alterations in both the quantity and functionality of immune cells. These include thymic involution, T cell exhaustion, epigenetic modifications, weakened immune responses, and a chronic low-grade inflammatory state. This review comprehensively analyzes the role of immunosenescence in elderly patients with advanced NSCLC and proposes potential therapeutic strategies to intervene in the immunosenescence process. By targeting immunosenescence, these strategies aim to inhibit the progression of NSCLC and improve the effectiveness of immunotherapy.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Immunotherapy ; Lung Neoplasms/genetics* ; Immunosenescence ; Aged

Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Ambient air pollution is increasingly being recognized as a risk factor for heart failure; however, its effects on cardiac biomarkers remain unclear. This scoping review assessed the existing evidence on the association between air pollution and cardiac biomarkers in heart failure, described the key concepts, synthesized data, and identified research gaps. Following the PRISMA-ScR guidelines, PubMed, Embase, Web of Science, and CNKI databases were searched for studies on air pollution, heart failure, and biomarkers. A total of 765 records were screened, and 81 full texts were assessed for eligibility, resulting in 15 studies. The results showed that the exposure to particulate matter was associated with elevated N-terminal pro-B-type natriuretic peptide and troponin levels. Several studies have linked particulate matter exposure to a higher cardiovascular risk and heart failure biomarkers. Inflammatory and oxidative stress markers were consistently elevated across studies, supporting the biological relevance of these associations. However, few studies have focused specifically on populations with heart failure or clinically relevant biomarkers, and the evidence for gaseous pollutants remains inconclusive. These findings highlight the need to integrate environmental risk assessment into heart failure care and inform policy efforts to reduce the pollution-related cardiovascular burden. Further research should address these gaps through improved exposure assessments and the integration of mechanistic evidence.
Heart Failure/epidemiology* ; Biomarkers/metabolism* ; Humans ; Air Pollution/adverse effects* ; Air Pollutants/adverse effects* ; Particulate Matter/adverse effects* ; Environmental Exposure ; Natriuretic Peptide, Brain/blood* ; Oxidative Stress ; Troponin/blood*

Objective:To analyze the results of lymphocyte subsets and 12 plasma cytokines in patients with tuberculosis by flow cytometry and to evaluate their diagnostic efficacy in these patients.Methods:This is a retrospective case-control study. A total of 128 patients with evidence of tuberculosis disease or clinically confirmed tuberculosis who were admitted to the 8th Medical Center of PLA General Hospital from January 2022 to December 2023 were included. According to the location of mycobacterium tuberculosis infection, the patients were divided into the pulmonary tuberculosis group (83 cases) and the extrapulmonary tuberculosis group (45 cases), and 100 healthy age-and sex matched people who underwent health check up during the study period were selected as the control group. Flow cytometry was used to detect peripheral blood lymphocyte subsets and 12 plasma cytokines [including 10 pro-inflammatory factors: interleukin (IL)-5, interferon (IFN)-α, IL-2, IL-6, IL-1β, IFN-γ, IL-8, IL-17, IL-12P70, Tumor necrosis factor (TNF)-α, and two anti-inflammatory factors: IL-4, IL-10] in participants of all groups. Spearman correlation method was used to analyze the correlation between lymphocyte subsets and cytokines, binary Logistic regression was used to screen the TB related factors, and receiver operating curve (ROC) was used to evaluate the diagnostic efficacy of TB related factors.Results:Compared with the control group, the absolute number of CD3 +T lymphocytes, CD3 +CD8 +T lymphocytes, CD3 +CD4 +T lymphocytes, NK cells and B cells were lower in pulmonary tuberculosis group and extrapulmonary tuberculosis group (all P<0.05). Except for IL-1β, the levels of other 11 cytokines are all significantly higher in the pulmonary tuberculosis group (all P<0.01), and the levels of IL-6, IFN-γ, IL-17, TNF-α, IL-4 and IL-10 were significantly higher in extrapulmonary tuberculosis group (all P<0.05). Compared with extrapulmonary tuberculosis group, the level of IL-8 was higher in pulmonary tuberculosis group ( P=0.026). Spearman correlation analysis showed that IL-6, IFN-γ and IL-8 were negatively correlated with the absolute numbers of CD3 +T lymphocytes, CD3 +CD8 +T lymphocytes, CD3 +CD4 +T lymphocytes, NK cells and B cells (IL-6: R2=-0.30, -0.28, -0.32, -0.26, -0.28; IFN-γ: R2=-0.36, -0.31, -0.37, -0.25, -0.36; IL-8: R2=-0.14, -0.13, -0.16, -0.14, -0.22; all P<0.05), IL-10 was negatively correlated with the absolute number of CD3 +CD4 +T lymphocytes, NK cells and B cells ( R 2=-0.14, -0.19, -0.21, all P<0.05); Binary Logistic regression analysis showed that IL-6, IFN-γ, IL-8 and IL-10 were the related factors of tuberculosis ( OR=1.809, 1.136, 0.910, 2.218, all P<0.05), ROC curve analysis showed that the AUC of IL-6, IFN-γ, IL-8 and IL-10 in the joint diagnosis of tuberculosis was 0.845, the sensitivity was 0.766, and the specificity was 0.820. Conclusion:The lower absolute number of lymphocyte subsets and cytokine levels in patients with pulmonary tuberculosis and extrapulmonary tuberculosis indicate that their immune function is in a low state, and the higher levels of pro-inflammatory factors (IL-6, IFN-γ, IL-8) and anti-inflammatory factor (IL-10) indicates the higher inflammatory status, and evaluation of these 4 cytokines has satisfactory diagnostic efficacy for tuberculosis.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.

Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.

Objective:To investigate the arsenic metabolism pattern and possible influencing factors in the population in drinking-water-borne endemic arsenic poisoning (drinking-water-borne arsenic poisoning for short) areas.Methods:In December 2004, a cluster sampling method was used to select arsenic poisoning population (arsenic poisoning group) and healthy population (control group) in drinking-water-borne arsenic poisoning area of Bayannur City, Inner Mongolia Autonomous Region as the survey subjects. A questionnaire survey was conducted. Arsenic content in drinking water at home of survey subjects, the levels of urinary arsenic and its metabolites, including [trivalent arsenic (As Ⅲ), inorganic arsenic (iAs), monomethylarsenic acid (pentavalent, MMA V), dimethylarsenic acid (pentavalent, DMA V), total arsenic (tAs), percentage of inorganic arsenic (iAs%), percentage of monomethylarsenic acid (MMA%), percentage of dimethylarsenic acid (DMA%), primary methylation index (PMI), secondary methylation index (SMI)] were tested using high performance liquid chromatography-inductively coupled plasma mass spectrometry; nail arsenic and nail selenium levels were tested using atomic fluorescence spectrometer. The influencing factors of arsenic metabolism pattern were analyzed by multiple linear regression. Results:A total of 536 survey subjects were included, including 155 individuals in the arsenic poisoning group and 381 in the control group. The water arsenic level ranged from 0.0 to 825.7 μg/L. Compared with the control group, there was no significant difference in the distribution of gender, education level and dental fluorosis in the arsenic poisoning group ( P > 0.05), but there were significant differences in the distribution of age, marital status, smoking, drinking and water arsenic ( P < 0.05). Compared with the control group, the levels of urinary As Ⅲ, iAs, MMA V, DMA V, tAs, MMA%, MMA/DMA and nail arsenic in the arsenic poisoning group were higher ( P < 0.05), while the levels of urinary DMA%, SMI and nail selenium were lower ( P < 0.05); but there was no statistically significant difference in the levels of urinary iAs% and PMI ( P > 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary As Ⅲ (β = - 19.82, - 23.83, 0.61, 0.21, 7.26, 2.98, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary tAs (β = 3.18, 3.25, 1.31, 15.59, P < 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary iAs (β = - 20.47, - 25.90, 0.64, 0.25, 7.87, 3.11, P < 0.05). Age, gender, education level, water arsenic and nail arsenic were the influencing factors of urinary MMA V (β = 0.52, - 17.07, - 21.84, 0.22, 2.77, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary DMA V (β = 2.35, 2.47, 0.85, 9.22, P < 0.05). Conclusions:Compared with healthy individuals, there are differences in arsenic metabolism pattern among individuals with drinking-water-borne arsenic poisoning. Age, gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic may be influencing factors of different arsenic metabolism patterns.

Rheumatoid arthritis （RA） is a chronic autoimmune disease with a complex pathogenesis. Immune dysfunction， synovial inflammation， and bone destruction are the key pathological links. The theory of "harmful hyperactivity and responding inhibition" is a high-level summary of the coordinated development of things in nature and the generation and restriction of the five elements and the six factors in nature. People and all things have the same origin， and the theory of "harmful hyperactivity and responding inhibition" represents the intrinsic regulation mechanism of the human body's homeostasis， reflecting the unity of opposites of "hyperactivity" and "inhibition" and emphasizing coordination and stabilization. In the pathogenesis of RA， the excessive immune response disrupts the normal body balance， which is closely related to the process of "hyperactivity becoming harmful". Synovial inflammation， tissue hyperplasia， and bone destruction are pathological results of the dysregulation of the body's immune self-stabilization function and can be regarded as the process of "failing to inhibition". Therefore， the theory of "hyperactivity harmful hyperactivity and responding inhibition" provides a unique perspective for understanding the modern pathological mechanisms of RA. Based on the theory of "harmful hyperactivity and responding inhibition" and the pathogenesis of RA， the author analyzed the modern medical basis of RA from the perspective of traditional Chinese medicine （TCM） and revealed the intrinsic connection between TCM pathogenesis such as insufficiency of vital energy and blood， strong defensive Qi and weak nutrient Qi， and intertwined phlegm and blood stasis and modern research on autoimmune disorders， synovial inflammation， and bone destruction. With the therapeutic criterion of "harm inhibition and responsible supporting"， the article summarized the mechanism of TCM in calming hyperactivity and supporting invincibility， which provided theoretical references for the clinical treatment of RA.