Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

BACKGROUND: In China, stroke burden remains severe as it is a major cause of mortality and disability. Detailed analyses across different subtypes will help optimize intervention strategies, enhance resource allocation efficiency, and ultimately reduce the overall disease burden. METHODS: We conducted a descriptive analysis of the incidence, prevalence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) of stroke and its subtypes using data (1990-2021) from the Global Burden of Disease (GBD) database. A Joinpoint regression model was applied to quantitatively analyze the indicators and calculate the annual percentage change (APC) and average annual percentage change (AAPC). We applied the Bayesian age-period-cohort (BAPC) model to project trends for 2022-2040. RESULTS: Incidence of stroke increased by 100.64% from 1990 to 2021, with ischemic stroke (IS) exhibiting the largest increase (201.13%) among all the subtypes, and the incidence being consistently higher in males than in females. The YLL/YLD ratio for stroke and its subtypes has decreased, with the YLL/YLD ratio falling from 20.13 to 9.48 in 1990-2021, indicating an increase in non-fatal burden. After adjusting for age, the age-standardized incidence rates (ASIRs) of stroke and its subtypes declined, except for IS. The age-standardized mortality rate (ASMR) for subarachnoid hemorrhage (SAH) decreased significantly (APC: -15.31%; 2000-2004), with the largest reduction in the age-standardized DALY rate (ASDR) also occurring during this period (APC: -14.22%). Furthermore, BAPC projections (2022-2040) indicate that stroke ASIRs in males will slightly decline but increase in females. Meanwhile, the ASIR of IS is expected to continue to rise. Overall, the ASMR and ASDR are projected to decline. CONCLUSIONS Although China has made some progress in stroke prevention and control, several challenges remain. Controlling IS must be prioritized, especially due to the high stroke burden among males.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective:To analyze the optical coherence tomography (OCT) imaging characteristics in patients with Coats disease and their value in predicting macular fibrosis.Methods:A nested case-control study was performed.A total of 43 patients (43 eyes) diagnosed with Coats disease through color fundus photography, ocular B-scan ultrasonography, fundus fluorescein angiography, and spectral-domain OCT examination were enrolled from January 2008 to October 2021 at the Xijing Hospital.Among them, there were 40 males and 3 females, aged from 2 to 60 years old, with a median age of 13 years.Macular fibrosis was used as an indicator of poor prognosis, and patients were divided into two groups based on whether macular fibrosis occurred at the end of follow-up.The differences in OCT characteristics between two groups were compared and logistic regression analysis was used to identify the risk factors for macular fibrosis.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Xijing Hospital of Fourth Military Medical University (No.KY20202009-C-1).Results:The OCT clinical features of 43 cases of Coats disease included intraretinal hard exudates in 43 eyes (100%), subretinal fluid in 21 eyes (48.8%), macular cysts in 17 eyes (27.9%), subretinal exudates in 9 eyes (20.9%), anterior retinal hyperreflective dots in 7 eyes (16.3%), epiretinal membrane in 21 eyes (48.8%), and intraretinal fluid in 22 eyes (51.2%).In color fundus photos of 41 eyes, 38 eyes (93.0%) had hard exudates distributed in the posterior pole and 27 eyes (65.9%) had the mid-peripheral region.OCT examination showed that hard exudates were distributed in the inner nuclear layer in 35 eyes (81.4%) and the outer nuclear layer in 33 eyes (76.7%).Among 21 eyes with exudative retinal detachment detected by OCT, 9 eyes (42.9%) were detected by fundus photography and 18 eyes (85.7%) were detected by B-scan ultrasonography.The proportions of eyes with subretinal fluid and subretinal exudates were higher in the macular fibrosis group than in the non-macular fibrosis group, and the differences were statistically significant ( χ2=20.755, P<0.001; χ2=6.133, P=0.013).Logistic regression analysis showed that the presence of subretinal fluid was a risk factor for macular fibrosis (odds ratio=48.345, 95% confidence interval: 4.272-547.066, P=0.002). Conclusions:OCT examination can detect subretinal fluid, subretinal exudates, macular cysts, macular exudates, and hyperreflective spots in the retina of patients with Coats disease.Subretinal fluid is a risk factor for macular fibrosis.

Objective:To assess the merits and demerits of placing small-sized tube as drainage compared with traditional drainage in patients after uniportal thoracoscopic lung wedge-resection.Methods:Patients who received uniportal video-assisted thoracoscopic surgery (U-VATS) lung wedge-resection were identified in our database. Patients placed small-sized tube drainage were compared with those placed traditional 28 Fr chest tube in terms of characteristics, perioperative outcomes. Propensity score matching was performed to balance the baseline of the patients.Results:Of the 178 enrolled patients, 121 were assigned to conventional tube group and 57 were assigned to small-sized tube group. After matching, 36 pairs of patients from the two groups were selected for statistical comparison. Compared with the traditional drainage group, the operation duration of the small-sized tube group was shorter[0.83(0.75, 1.04)h vs.1.08(0.96, 1.41)h, P=0.003], intraoperative blood loss was less [5(5, 10) ml vs. 10(7.5, 10) ml, P=0.001), postoperative total drainage volume was less[67.5(30, 190)ml vs.175(120, 365)ml, P<0.001], and postoperative pain score was lower[0.3(0.3, 0.7) vs.0.7(0.3, 2.2), P<0.05]. No significant difference was observed in the incidence of small amount of pneumothorax or small amount of pleural effusion before extubation between the two groups. The incidence of postoperative complications was relatively low and there was no significant difference between the two groups. Conclusion:Compared to conventional chest tube, small-sized tube for postoperative drainage after U-VATS lung wedge-resection, may be a feasible and promising approach to reduce postoperative pain and promote recovery.

Objective:To explore the influence of pulmonary nodule size, nodule location, fissure, surgical approach, surgical entrance, postoperative pathology, surgical method and other factors on the relevant information of basal segmentectomy under thoracoscopy.Methods:Retrospectively analyze 103 patients who underwent thoracoscopic basal segmentectomy of the lung from January 2023 to February 2024. According to the classification of nodule size, nodule position, development of pulmonary fissure, surgical approach, number of surgical entrance, postoperative pathology, surgical method, tc., the influence of single factor Logistic regression analysis was used to explore the influence of various factors on the relevant information of pulmonary basal segmentectomy under thoracoscopy. Results:When the dependent variable was the surgery duration, single factor analysis showed that CT location( P=0.024), nodule composition( P=0.029), surgical entry( P=0.002), surgical method( P<0.001), and surgical approach( P=0.052) significantly influenced the surgery duration. Variables with P<0.1 in the single factor analysis were included in the multivariate analysis, which showed that surgical entry and surgical method significantly influenced surgery duration( P<0.05). When the dependent variable was the total hospitalization cost, single factor analysis showed that CT location, surgical approach, and surgical method significantly influenced the total hospitalization cost( P<0.1). Multiple factor analysis showed that the surgical method affected the total hospitalization cost, with significantly higher costs when S9 or S10 lung segments were resected( P=0.050). When the dependent variable was postoperative drainage duration, single factor analysis showed that the condition of the lung fissures significantly influenced postoperative drainage duration( P=0.028). Multiple factor regression analysis showed that incomplete lung fissure development significantly increased the possibility of postoperative air leaks( P=0.034). Conclusion:The surgical access may significantly affect the operation time, which is the use of uniport thoracoscopy is shorter than the multi-port operation time, the surgical method does not contain S9/S10 is shorter than that of S9/S10, and the total cost of hospitalization is lower. The completeness of the fissure will significantly decrease the possibility of postoperative pulmonary leakage.

Objective:To explore whether lung microorganisms influence the occurrence and development of early lung adenocarcinoma by analyzing the presence and changes of local microorganisms in early lung adenocarcinoma.Methods:Tumor tissues and alveolar lavage fluid were collected from 32 patients diagnosed with lung adenocarcinoma at the China-Japan Friendship Hospital. Nextseq550DX was used for DNA sequencing. R language was used to calculate the number of microorganisms in the tumor tissue and alveolar lavage fluid samples of different stages and grades. species and diversity, and use statistical methods such as TSEA and LEfSe analysis to compare the diversity and differences of microorganisms in different groups. Results:Both Actinobacteria and Proteobacteria accounted for a higher proportion in both the tumor tissue and alveolar lavage fluid samples of patients with lung adenocarcinoma. The number of microorganisms detected in the tumor tissue was greater than that in the lavage fluid, and the alpha diversity was higher, but the difference Not significant( P<0. 05). According to the analysis of differences in lung microorganisms in patients with different pathological grades: In the two samples, invasive adenocarcinoma has more microorganisms than carcinoma in situ + microinvasive carcinoma, and the alpha diversity of the lavage fluid is significantly higher, and the comparison between the groups is statistically significant( P=0. 011); the difference in β diversity was not statistically significant( P>0. 05). Group analysis based on different pathological types: the invasive adenocarcinoma group samples showed a decrease in Proteobacteria, the carcinoma in situ + minimally invasive cancer group was mainly composed of Proteobacteria, and most of the microorganisms related to lung cancer differences analyzed in each group belonged to Proteobacteria and Actinobacteria. Phylum. Conclusion:Most of the microbes in tumor tissues and lavage fluid of lung adenocarcinoma belong to the Actinobacteria and Proteobacteria. Most of the differentially associated microbes of lung cancer under different classifications also belong to Proteobacteria and Actinobacteria, which are the main characteristics of lung microbial composition in patients with early-stage lung adenocarcinoma.

Objective To investigate the longitudinal association between alcohol abstinence and accelerated biological aging among middle-aged and older adults and to explore the potential effect modifiers influencing the association.Methods Utilizing the clinico-biochemical and anthropometric data from the baseline and first repeat survey of the UK Biobank(UKB),we employed the Klemera and Doubal method(KDM)to construct the biological age(BA)and calculate BA acceleration.Change analysis based on multivariate linear regression models was employed to explore the association between changes in alcohol abstinence and changes in BA acceleration.Age,sex,smoking status,tea and coffee consumption,and body mass index were considered as the stratification factors for conducting stratified analysis.Results A total of 5 412 participants were included.Short-term alcohol abstinence(β=1.00,95%confidence interval[CI]:0.15-1.86)was found to accelerate biological aging when compared to consistent never drinking,while long-term abstinence(β=-0.20,95%CI:-1.12-0.71)did not result in a significant acceleration of biological aging.Body mass index may be a potential effect modifier.Conclusion Short-term alcohol abstinence was associated with accelerated biological aging,but the effect gradually diminishes over extended periods of abstinence.