Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Tailoring the Molecular Planarity of Perylene Diimide-Based Third Component toward Efficient Ternary Organic Solar Cells.

Incorporating a third component into binary organic solar cells (b-OSCs) has provided a potential platform to boost power conversion efficiency (PCEs). However, gaining control over the non-equilibrium blend morphology via the molecular design of the perylene diimide (PDI)-based third component toward efficient ternary organic solar cells (t-OSCs) still remains challenging. Herein, two novel PDI derivatives are developed with tailored molecular planarity, namely ufBTz-2PDI and fBTz-2PDI, as the third component for t-OSCs. Notably, after performing a cyclization reaction, the twisted ufBTz-2PDI with an amorphous character transferred to the highly planar fBTz-2PDI followed by a semi-crystalline character. When incorporating the semi-crystalline fBTz-2PDI into the D18:L8-BO system, the resultant t-OSC achieved an impressive PCE of 18.56%, surpassing the 17.88% attained in b-OSCs. In comparison, the addition of amorphous ufBTz-2PDI into the binary system facilitates additional charge trap sites and results in a deteriorative PCE of 14.37%. Additionally, The third component fBTz-2PDI possesses a good generality in optimizing the PCEs of several b-OSCs systems are demonstrated. The results not only provided a novel A-DA'D-A motif for further designing efficient third component but also demonstrated the crucial role of modulated crystallinity of the PDI-based third component in optimizing PCEs of t-OSCs.

Innovative pancreas-guided technique for splenic flexure mobilization in laparoscopic left hemicolectomy.

OBJECTIVE: Splenic flexure mobilization (SFM) is a major challenge in laparoscopic left hemicolectomy. This study aims to assess the safety and effectiveness of the pancreas-guided SFM technique during laparoscopic left hemicolectomy. METHODS: From January 2018 to December 2023, 352 patients with left-sided colon cancer underwent laparoscopic left hemicolectomy. Based on the SFM method used, the patients were divided into the pancreas-guided group (167 cases) or the "Three Approaches Roundabout"/classic group (185 cases). Clinicopathologic characteristics and intraoperative and postoperative variables were compared between the two groups. RESULTS: The two groups had no significant differences in baseline indicators (P > 0.05). All surgeries were successful without needing to convert to laparotomy, and there were no combined organ resections involving the spleen or pancreas in either group. The mean duration of surgery was significantly lower in the pancreas-guided group than in the classic group (P < 0.01). The median volume of intraoperative blood loss in the pancreas-guided group was lower than that in the classic group (P < 0.01). Through video playback, it was found that the retro-pancreatic space had been entered during operation in 8 cases (4.3%) in the classic group, while there were no such occurrences in the pancreas-guided group. This difference was statistically significant (P < 0.05). The difference in the number of lymph nodes cleared, postoperative hospital stays, and incidence of complications were not statistically significant (all P > 0.05) between the groups. CONCLUSION: The pancreas-guided SFM technique is a safe and feasible option for laparoscopic left hemicolectomy. Our study's findings suggest that this approach facilitates accurate access to the correct anatomic plane, potentially improving surgical efficiency.

Global trends and partial forecast of adverse effects of medical treatment from 1990 to 2019: an epidemiological analysis based on the global burden of disease study 2019.

BACKGROUND: The possibility of adverse effects of medical treatment (AEMT) is increasing worldwide, but little is known about AEMT in China. This study analyzed the health burden of AEMT in China in recent years through the Global Burden of Disease Study (GBD) 2019 and compared it with the worldwide average level and those in different sociodemographic index (SDI) regions. METHODS: We calculated the age-standardized rate (ASR) of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), incidence and prevalence attributed to AEMT in China, worldwide and countries with different sociodemographic indices during 1990-2019 using the latest data and methods from the GBD 2019. RESULTS: From 1990 to 2019, the global age-standardized death rate (ASDR), DALYs, and YLLs for AEMT showed a significant downward trend and were negatively associated with the SDI. By 2040, the ASDR is expected to reach approximately 1.58 (95% UI: 1.33-1.80). From 1990 to 2019, there was no significant change in the global incidence of AEMT. The occurrence of AEMT was related to sex, and the incidence of AEMT was greater among females. In addition, the incidence of AEMT-related injuries and burdens, such as ASR of DALYs, ASR of YLLs and ASR of YLDs, was greater among women than among men. Very old and very young people were more likely to be exposed to AEMT. CONCLUSIONS: From 1990 to 2019, progress was made worldwide in reducing the harm caused by AEMT. However, the incidence and prevalence of AEMT did not change significantly overall during this period. Therefore, the health sector should pay more attention to AEMT and take effective measures to reduce AEMT.

A Principal Component Regression-Based Electrophysiological Study of Patients with Severe Infections.

Objective: Severe infections can lead to neuromyopathy in critically ill patients, resulting in limb weakness and difficulty in weaning from a ventilator. This study aims to assess the electrophysiological test results in patients with severe infection and their correlation with severity scores (APACHE II and SOFA). Methods: Thirty-one patients with severe infection in the EICU were prospectively studied. Factor analysis and principal component regression were applied to develop linear models of electrophysiological diagnostic outcomes with APACHE II and SOFA scores for the entire patient cohort, the younger group (age<55) cohort, and the older group (age>55) cohort of patients with severe infections, respectively. Results: Among patients with a severe infection in the EICU, the proportion of patients without critical neuromyopathy with more than 50% F-wave presence in the median, ulnar, and tibial nerves (64.9%, 56.8%, 48.6%, respectively) was significantly higher than in the group with critical neuromyopathy (52.1%, 35.4%, 29.2%, respectively.), and the proportion of patients with critical neuromyopathy who did not elicit the three types of F wave was significantly higher in the cohort of patients with critical neuromyopathy (40.5%, 32.4%, 35.1%, respectively.) were significantly higher than in the cohort of patients without critical illness (18.8%, 12.5%, 20.8%, respectively). In addition, on average, patients with critical neuromyopathy had a much lower CMAP for the median nerve (wrist, elbow) (2.4, 1.88, respectively) (4.3, 3.9, respectively in undiagnosed cohort), ulnar nerve (wrist, elbow) (2.4, 1.88, respectively) (5.65, 5.4, respectively in undiagnosed cohort), and tibial nerve(ankle, popliteal fossa) (2.7, 1.57, respectively)(6.55, 5.3, respectively in undiagnosed cohort) nerves than patients without critical neuromyopathy, and showed more non-elicitation, which was not seen in the cohort of patients without critical neuromyopathy. The CMAP returned to normal in the cohort of patients without critical neuromyopathy. Therefore, with respect to our selected electrophysiological parameters, the two patient groups showed significant differences in terms of the specific values and statistical analysis (Table 1). Through factor analysis and principal component regression, we found that CMAP and F-wave were highly correlated with APACHE II and SOFA scores, and the correlation between the electrophysiological wave spectrum and the two scores was further quantified by principal component regression. Conclusion: Electrophysiological spectroscopy can serve as an early warning for the development of neuromuscular disease in EICU patients. Abnormal electrophysiological diagnosis prior to actual neuromuscular abnormalities and its subsequent return to normal can help identify high-risk patients and implement early interventions.

City-level synergy and co-benefits of mitigating CO2 emissions and air pollution in China.

Synergistic control of carbon emissions and pollutant concentrations can efficiently tackle climate change and air pollution. The synergistic performance and co-benefits yielded by controlling these factors are urgent and critical issues in China. Accordingly, a comprehensive indicator for assessing synergistic performance is pioneered, and co-benefits of mitigating CO2 and PM2.5 in Chinese cities are evaluated. Chinese synergistic performance is dominated by CO2 variations. In 2015-2020, multiple northeastern, central, southern, and eastern cities exhibited synergistic effects by greatly reducing CO2 emissions. The synergistic performance thereafter leads to co-benefits through environmental and economic feedbacks. The CO2 and PM2.5 controls in Northeast Chinese cities feature the most profound co-benefits of approximate 4800 CNY per capita, with each contributing 72 % and 28 %, respectively, to this total. The findings provide intercity synergistic performance and scientific support for policymaking.

The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.

The CBL (Casitas B-lineage lymphoma) family, as a class of ubiquitin ligases, can regulate signal transduction and activate receptor tyrosine kinases through various tyrosine kinase-dependent pathways. There are three members of the family: c-CBL, CBL-b, and CBL-c. Numerous studies have demonstrated the important role of CBL in various cellular pathways, particularly those involved in the occurrence and progression of cancer, hematopoietic development, and regulation of T cell receptors. Therefore, the purpose of this review is to comprehensively summarize the function and regulatory role of CBL family proteins in different human tumors, as well as the progress of drug research targeting CBL family, so as to provide a broader clinical measurement strategy for the treatment of tumors.

Elevated CD4+ T Cell Senescence Associates with Impaired Immune Responsiveness in Severe COVID-19.

Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may impact vaccine efficacy. However, whether the senescence of T cells is associated with severe COVID-19 outcome in elderly individuals is unclear. Using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in peripheral blood from 100 hospitalized elderly COVID-19 patients and compared differences between those with mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit, and ELISPOT assay respectively, the cytokine production profile of COVID-19 reactive T cells, and plasma soluble factors by cytometric bead array (CBA). Our study found a significantly elevated level of CD4+ Tsens in patients with severe/critical disease compared to those with mild/moderate illness. Patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate compared to those with a lower level (≤19.78%). This is more pronounced among patients with breakthrough infections. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability, and COVID-19 reactive IL-2+CD4+ T cells. In addition, spike-specific antibody levels were positively correlated with IL-2 producing T cells and plasma IL-2 amount. Mechanistically, with defective CD40L, T cells from patients with CD4+ Tsens >19.78% were unable to support B cell proliferation and differentiation. Our data demonstrate that the percentage of CD4+ Tsens in peripheral blood may serve as a reliable biomarker for the prognosis of severe COVID-19 patients, especially in breakthrough infections. Therefore, restoring the immune response of CD4+ Tsens may be key to preventing severe illness and improving vaccine efficacy in older adults.

Symptoms and medical resource utilization of patients with bronchiectasis after SARS-CoV-2 infection.

Background: The impact of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients with bronchiectasis in terms of symptoms, self-management and medical resource utilization was unknown. Objective: To describe the impact of infection by SARS-CoV-2 on fluctuation of symptoms, self-management and medical resource utilization of patients with bronchiectasis during the pandemic of COVID-19. Methods: This was a single-center cross-sectional questionnaire study performed in Peking University Third Hospital. An online questionnaire investigation addressing the impact of SARS-CoV-2 infection on respiratory symptoms, self-management and medical resource utilization was conducted among patients with bronchiectasis during the COVID-19 surge in December 2022 in Beijing, China. Results: Five hundred patients with bronchiectasis, with 285 (57%) females, and a mean (±SD) age of 57.9 ± 15.1 years, completed the telephone questionnaire. The reported prevalence of COVID-19 was 81.2% (406/500). Of the 406 COVID-19 patients, 89.2% experienced fever lasting mostly for no more than 3 days, 70.6 and 61.8% reported exacerbated cough and sputum production respectively, and 17.7% reported worsened dyspnea. Notable 37.4% of the patients with COVID-19 experienced symptoms consistent with the definition of an acute exacerbation of bronchiectasis. However, 76.6% (311/406) of the infected patients did not seek medical care but managed at home. Of the patients who visited hospitals, 26.3% (25/95) needed hospitalization and 2.1% (2/95) needed ICU admission. Multi-factors logistic regression analysis showed that younger age (p = 0.012) and not using a bronchodilator agent(p = 0.022) were independently associated with SARS-CoV-2 infection, while a history of exacerbation of bronchiectasis in the past year (p = 0.006) and daily use of expectorants (p = 0.002) were associated with emergency visit and/or hospitalization for patients with bronchiectasis after SARS-CoV-2 infection. Conclusion: During the COVID-19 surge, the infection rate of SARS-CoV-2 in patients with bronchiectasis was high, and most of the patients experienced new-onset or exacerbated respiratory symptoms, but only a minority needed medical visits. Our survey results further underscore the importance of patients' disease awareness and self-management skills during a pandemic like COVID-19.