Utilizing machine learning for early screening of thyroid nodules: a dual-center cross-sectional study in China.

Background: Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on ultrasound features. This study explores machine learning for screening using demographic and biochemical indicators. Methods: Analyzing data from 6,102 individuals and 61 variables, we identified 17 key variables to construct models using six machine learning classifiers: Logistic Regression, SVM, Multilayer Perceptron, Random Forest, XGBoost, and LightGBM. Performance was evaluated by accuracy, precision, recall, F1 score, specificity, kappa statistic, and AUC, with internal and external validations assessing generalizability. Shapley values determined feature importance, and Decision Curve Analysis evaluated clinical benefits. Results: Random Forest showed the highest internal validation accuracy (78.3%) and AUC (89.1%). LightGBM demonstrated robust external validation performance. Key factors included age, gender, and urinary iodine levels, with significant clinical benefits at various thresholds. Clinical benefits were observed across various risk thresholds, particularly in ensemble models. Conclusion: Machine learning, particularly ensemble methods, accurately predicts thyroid nodule presence using demographic and biochemical data. This cost-effective strategy offers valuable insights for thyroid health management, aiding in early detection and potentially improving clinical outcomes. These findings enhance our understanding of the key predictors of thyroid nodules and underscore the potential of machine learning in public health applications for early disease screening and prevention.

Evolution of black carbon and brown carbon during summertime in Southwestern China: An assessment of control measures during the 2023 Chengdu Summer World University Games.

The 31st FISU Summer World University Games (SWUG) was held in Chengdu, southwestern China, from July 22 to August 8, 2023. A series of control measures were carried out to ensure good air quality during the SWUG, providing an opportunity to investigate the atmospheric behaviors of light-absorbing aerosols under such a substantial disturbance caused by the control measures. To assess the impacts of emission controls on primary pollutants, a field campaign was conducted at a rural site in Chengdu to investigate the characterization of equivalent black carbon (eBC). The changes of eBC concentrations before, during, and after the SWUG were characterized. The sources of eBC were resolved, and the impacts of atmospheric processes on the absorption capacity were also investigated. During the SWUG, the eBC concentration decreased by 12.1 % and 25.3 % compared with those before and after the SWUG. A fossil fuel combustion (eBCff) and a biomass burning (eBCbb) originated eBC were resolved using the aethalometer model. Both eBCff and eBCbb decreased during the SWUG, indicating the effectiveness of control measures. After the SWUG, the influence of biomass burning emissions became more and more significant, and the contribution of brown carbon (BrC) to light absorption at 370-660 nm increased by 52, 19, 7, 6, and 17 % compared to those during the SWUG. As the biomass burning emitted aerosols aged, the absorption Ångström exponent and babs(BrC370nm) decreased gradually, which was mainly due to the photobleaching of the chromophores during the daytime. eBCff was mainly affected by strong wind, while high eBCbb concentration was mainly attributed to the gradual accumulation of biomass-burning emissions near the observation site. The results show the significant reduction of eBC with the implementation of the air pollution mitigation campaign, and provide insights on the impacts of atmospheric processes on BC optical properties during summertime.

Disease types and pathogenic mechanisms induced by PM2.5 in five human systems: An analysis using omics and human disease databases.

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.

Neutrophil in the suppressed immune microenvironment: Critical prognostic factor for lung adenocarcinoma patients with KEAP1 mutation.

Purpose: It is still unclear whether KEAP1 mutation is detrimental to immunotherapy of lung adenocarcinoma (LUAD) patients, we try to analyse the exact changes in the TME in LUAD patients with KEAP1 mutations and to identify key factors influencing prognosis. Experimental design: A total of 1,029 patients with lung squamous carcinoma (LUSC) or LUAD with data obtained from The Cancer Genome Atlas were included in this study. The TME and OS of patients with LUAD stratified by mutant versus wild-type KEAP1 status were comprehensively measured. Moreover, we classified LUAD patients with KEAP1 mutations into three subtypes, by unsupervised consensus clustering. We further analysed the TME, OS, commutated genes and metabolic pathways of different subgroups. A total of 40 LUAD patients underwent immunotherapy were collected and classified into mutant KEAP1 group and wild-type KEAP1 group. We also conducted immunohistochemical staining in KEAP1-MT groups. Result: Suppressed TME was observed not only in LUAD patients but also in LUSC patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than wild-type KEAP1. Unsupervised consensus clustering analysis suggested that the three subtypes of patients exhibited different densities of neutrophil infiltration and had different OS results: cluster 2 patients had significantly higher levels of neutrophils had significantly worse prognoses than those of patients in clusters 1 and 3 and patients with wild-type KEAP1. Univariate and multivariate Cox analyses proved that a high density of neutrophils was significantly associated with worse OS and immunohistochemical staining proved that shorter PFS showed high density of neutrophils. Conclusion: KEAP1 mutation significantly suppresses the tumour immune microenvironment in LUAD patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than with wild-type KEAP1. Neutrophils may play an important role in the prognosis of LUAD patients with KEAP1 mutations and may provide a promising therapeutic target.

Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment.

Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.

Foveapeltis gen. nov., an unusual cleroid genus with large hypomeral cavities from mid-Cretaceous amber (Coleoptera: Cleroidea).

Beetles have a remote evolutionary history dating back to the Carboniferous, with Mesozoic fossils playing a pivotal role in elucidating the early evolution of extant families. Despite their exceptional preservation in amber, deciphering the systematic positions of Mesozoic trogossitid-like beetles remains challenging. Here, we describe and illustrate a new trogossitid-like lineage from mid-Cretaceous Kachin amber, Foveapeltis rutai Li, Kolibác, Liu & Cai, gen. et sp. nov. Foveapeltis stands out within the Cleroidea due to the presence of a significant large cavity on each hypomeron. While the exact phylogenetic placement of Foveapeltis remains uncertain, we offer a discussion on its potential affinity based on our constrained phylogenetic analyses.

Rescue Therapies for Steroid-Refractory Acute Severe Ulcerative Colitis: A Systemic Review and Network Meta-analysis.

BACKGROUND AND AIMS: Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis (steroid-refractory (SR) ASUC) requires colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC. METHODS: Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5 mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo. RESULTS: Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates. CONCLUSION: This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.

Prevalence of subthreshold depression and its related factors in Chinese college students: A cross-sectional study.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

Self-supervised tomographic image noise suppression via residual image prior network.

Computed tomography (CT) denoising is a challenging task in medical imaging that has garnered considerable attention. Supervised networks require a lot of noisy-clean image pairs, which are always unavailable in clinical settings. Existing self-supervised algorithms for suppressing noise with paired noisy images have limitations, such as ignoring the residual between similar image pairs during training and insufficiently learning the spectrum information of images. In this study, we propose a Residual Image Prior Network (RIP-Net) to sufficiently model the residual between the paired similar noisy images. Our approach offers new insights into the field by addressing the limitations of existing methods. We first establish a mathematical theorem clarifying the non-equivalence between similar-image-based self-supervised learning and supervised learning. It helps us better understand the strengths and limitations of self-supervised learning. Secondly, we introduce a novel regularization term to model a low-frequency residual image prior. This can improve the accuracy and robustness of our model. Finally, we design a well-structured denoising network capable of exploring spectrum information while simultaneously sensing context messages. The network has dual paths for modeling high and low-frequency compositions in the raw noisy image. Additionally, context perception modules capture local and global interactions to produce high-quality images. The comprehensive experiments on preclinical photon-counting CT, clinical brain CT, and low-dose CT datasets, demonstrate that our RIP-Net is superior to other unsupervised denoising methods.

An easy-to-perform method for microvessel isolation and primary brain endothelial cell culture to study Alzheimer's disease.

Dysfunction of the blood-brain barrier (BBB) has been increasingly recognised as a critical early event in Alzheimer's disease (AD) pathophysiology. Central to this mechanism is the impaired function of brain endothelial cells (BECs), the primary structural constituents of the BBB, the study of which is imperative for understanding AD pathophysiology. However, the published methods to isolate BECs are time-consuming and have a low success rate. Here, we developed a rapid and streamlined protocol for BEC isolation without using transgenic reporters, flow cytometry, and magnetic beads, which are essential for existing methods. Using this novel protocol, we isolated high-purity BECs from cell clusters of cortical microvessels from wild-type and APPswe/PS1dE9 (APP/PS1, a classical AD model) mice at 2, 4 and 9 months of age. Reduced levels of tight junction proteins Claudin-5 and Zonula Occludens-1, as well as glucose transporter 1, were observed in the isolated cortical microvessels from APP/PS1 mice and amyloid-ß (Aß) oligomer-treated BECs from wild-type mice. Trans-well permeability assay showed increased FITC-dextran leakage in BECs treated with Aß, suggesting impaired BBB permeability. BECs obtained using our novel protocol can undergo various experimental analyses, including immunofluorescence staining, western blotting, real-time PCR, and trans-well permeability assay. In conclusion, our novel protocol represents a reliable and valuable tool for in vitro modelling BBB to study AD-related mechanisms and develop targeted therapeutic strategies.

Case report: dose-dependent interaction between dexamethasone and voriconazole in severely ill patients with non-Hodgkin's lymphoma being treated for invasive pulmonary aspergillosis.

Background: Voriconazole is primarily metabolized by CYP2C19 and CYP3A4. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted voriconazole concentrations. Case summary: In this case report, we describe the case of a 64-year-old man who was treated for non-Hodgkin's lymphoma with continuous glucocorticoids co-administrated with voriconazole against invasive pulmonary aspergillosis. A decrease in trough concentration (Cmin) of voriconazole was observed and related with co-administration of dexamethasone in the patient carrying the CYP2C19 *1*2 genotype: voriconazole Cmin/dose ratios of 0.018 (0.1 mg L-1/5.7 mg kg-1 day-1), 0.18 (1 mg L-1/5.7 mg kg-1 day-1), and 0.23 (2 mg L-1/8.6 mg kg-1 day-1) at dexamethasone doses of 20, 12.5, and 2.5 mg, respectively. Sub-therapeutic voriconazole Cmin was associated with high- and moderate-dose dexamethasone (20 and 12.5 mg), leading to failure of antifungal treatment. Conclusion: The extent of voriconazole-dexamethasone interaction was determined by the dose of dexamethasone and associated with the CYP2C19 *1*2 genotype. Therapeutic drug monitoring of voriconazole is necessary to avoid clinically relevant interactions for optimal antifungal therapy.

Association between surgical delays for femoral neck fractures and early postoperative complications in young and middle-aged adults: A study based on the national inpatient sample database.

BACKGROUND: Femoral neck fractures (FNF) in young and middle-aged adults are primarily caused by high-energy injuries in traffic accidents. Surgical delays often occur due to transportation issues, preoperative evaluations, and economic burdens. METHODS: A retrospective analysis was conducted on young and middle-aged FNF patients undergoing reduction and internal fixation surgeries from 2010 to 2019 with the use of the National Inpatient Sample database. Logistic regression analysis was used to assess the relationship between surgical delays and complications, and the independent risk factors contributing to delays. Categorical variables were investigated via a chi-square test, while continuous variables including Elixhauser Comorbidity Index (ECI) scores, length of hospital stay (LOS), and total medical costs were analyzed via t-test or rank-sum test. RESULTS: 9,204 patients undergoing reduction and internal fixation surgeries were included. In the delayed group, patients had higher ECI scores, longer hospital stays, higher expenses, and increased inpatient mortality (1.61% vs. 0.28 %, P < 0.0001). Longer surgical delays were associated with higher risks of complications, including femoral head osteonecrosis, internal fixation loosening and breakage, and respiratory complications. Fluid and electrolyte disorders, metastatic cancer, pulmonary circulation disorders, and renal failure were identified as independent risk factors for surgical delays. Except for anemia (OR=2.37, P < 0.0001), no significant differences in early postoperative complications were found between open-reduction and closed-reduction internal fixation (ORIF/CRIF) surgeries. CONCLUSION: Early surgical intervention, within a 2-days period after injury, seems to be crucial for young adults with FNF. If CRIF is challenging in some cases, ORIF can be another choice.

Photoelectrochemical analysis of Pb2+ based on Au@PTCA Schottky junction with Pb2+-G quadruplex structure.

Herein, a novel photoelectrochemical (PEC) aptasensor using gold nanoparticles@3,4,9,10-perylene tetracarboxylic (Au@PTCA) Schottky junction as the effective optoelectronic material and lead ion (Pb2+)-G quadruplex structure as the efficient quencher was constructed for the detection of Pb2+ with high sensitivity and excellent selectivity. Au@PTCA Schottky junction, which was proposed by the in situ reduction of Au NPs on the PTCA surface, exhibited a strong unidirectional conductivity, which could generate a significantly enhanced PEC signal compared with the pure PTCA. The Pb2+-G quadruplex structure with a large spatial hindrance effect was formed when the target Pb2+ was present owing to the occurrence of the specific recognition between Pb2+ and its aptamer S1. The formation of a Pb2+-G quadruplex structure effectively quenched the initial signal generated by the Au@PTCA Schottky junction, which was derived from restricted electron transport and light transmission. The obtained prominently decreased PEC signal could achieve the quantitative detection of Pb2+ from 0.5 pM to 500 nM, with a low detection limit of 0.17 pM. The preparation time of this PEC aptasensor was 13 h, and the time for PEC measurement depended on the illumination time, which switched off-on-off for 10 s-20 s-10 s. The study proposed here with high sensitivity and excellent selectivity for Pb2+ analysis offered a novel and reliable tool for environmental monitoring related to heavy metal ions.

Mode-Symmetry-Assisted Optical Pulling by Bound States in the Continuum.

Aside from optical pushing and trapping that have been implemented successfully, the transportation of objects backward to the source by the optical pulling forces (OPFs) has attracted tremendous attention, which was usually achieved by increasing the forward momentum of light. However, the limited momentum transfer between light and object greatly constrains the amplitudes of OPFs. Here, we present a mechanism to generate strong interactions between object and background through the bound states in the continuums, which can generate large OPFs without increasing the forward momentum of light. The underlying physics is the extraction of momentum from the designed background lattice units assisted by mode symmetry. This work paves the way for extraordinary optical manipulations and shows great potential for exploring the momenta of light in media.

Ichthyosis uteri complicated by endometrial adenocarcinoma with transitional cell differentiation: A case report.

RATIONALE: Ichthyosis uteri is a rare pathological condition characterized by the replacement of the endometrial lining by stratified squamous epithelium. Yet its occurrence with endometrial adenocarcinoma is very rare. PATIENT CONCERNS: A 68-year-old woman has been experiencing sporadic, minor vaginal hemorrhages for a few months. The gynecological evaluation revealed a uterine enlargement and imaging demonstrated an irregular mass within the uterus. DIAGNOSIS: Endometrial adenocarcinoma with transitional cell differentiation; ichthyosis uteri with dysplasia. INTERVENTIONS: Radical hysterectomy with pelvic lymphadenectomy was performed followed by postoperative radiotherapy. OUTCOMES: Postoperative follow-up at 8 months showed a favorable outcome without signs of recurrence and metastasis. LESSONS: Adequate pathological sampling is crucial to identifying the accompanying lesions of ichthyosis uteri. Finding molecular alterations in various pathological morphologies is important to understand the evolution of disease.

The association between lipid accumulation products and depression in U.S. adults: A cross-sectional study from NHANES 2005-2018.

OBJECTIVE: To investigate the potential correlation between lipid accumulation products (LAP) and depression in adults in the United States. METHODS: We analyzed data from 13,051 participants from the NHANES 2005-2018 cycle. The LAP index was calculated using the waist circumference (WC) and serum triglyceride (TG) levels, which reflect lipid toxicity. Participants who scored ≥10 on the patient health questionnaire-9 (PHQ-9) were considered depressed. Multivariate logistic regression analyses were conducted to explore the association between the LAP index and depression. Furthermore, we conducted subgroup analysis to identify potentially sensitive populations. Smoothed curve fitting and generalized additive model (GAM) regression were performed to verify the association between the LAP index and depression. RESULTS: A total of 13,051 participants were eligible for analysis. After adjusting for all potential confounders, the risk of depression tended to increase with an increasing LAP index (odds ratio [OR]: 1.0011, 95% confidence interval [CI]: 1.0001, 1.0021). Compared to participants with LAP quartile 1, participants with LAP quartile 3 exhibited the highest risk of depression (OR: 1.43, 95%CI: 1.03, 1.99). Subgroup analysis demonstrated a strong association between the LAP index and depression in men (OR: 1.002, 95%CI: 1.001, 1.004) or those with hypertension (OR: 1.002, 95%CI: 1.000, 1.003). Additionally, smoothed curve fitting and GAM regression demonstrated a positive linear correlation between the LAP index and depression. CONCLUSIONS: Our findings suggest that individuals with a higher LAP index may be at higher risk of depression, particularly men or those with hypertension. However, further studies are required to confirm these findings.

The up-regulation of PD-L1 during boningmycin-induced senescence in human cancer cells depends on the activation of the JAK/STAT signaling pathway mediated by SASP.

Therapy-induced senescence can regulate both the innate and adaptive immune systems, thereby affecting therapeutic efficacy. Bleomycin is a major component of combined chemotherapy regimens, utilized for the treatment of multiple tumors, whereas pulmonary toxicity severely restricts its clinical benefits. As a member of the bleomycin family, boningmycin (BON) exhibits potent anticancer activity with minimal pulmonary toxicity, making it a potential alternative to bleomycin. Low concentrations of BON can induce senescence, but the impact of BON-induced senescence on anticancer immunity remains unclear. This study investigates the effects of BON-induced senescence on PD-L1 expression and the underlying mechanisms in human cancer cells. Firstly, the elevation of PD-L1 protein during BON-induced senescence was confirmed by a senescence ß-galactosidase staining assay, detection of the senescence-associated secretory phenotype (SASP), western blot and flow cytometry in human lung cancer NCI-H460 cells and breast cancer MDA-MB-231 cells. Subsequently, it was shown that the increase in PD-L1 protein is mediated by SASP, as evidenced by the use of conditional media, knockdown of cyclic GMP-AMP synthase and inhibition of stimulator of interferon genes. Ultimately, it was demonstrated that SASP-mediated PD-L1 up-regulation is dependent on the activation of the JAK/STAT pathway through the use of specific inhibitors and siRNAs. These findings clarify the impact of BON-induced senescence on PD-L1 expression and may contribute to the optimization of the therapeutic efficacy of bleomycin-related compounds and the clinical transformation of BON.

Impact of Ambient Temperature on Mortality Burden and Spatial Heterogeneity in 16 Prefecture-Level Cities of a Low-Latitude Plateau Area in Yunnan Province: Time-Series Study.

Background: The relation between climate change and human health has become one of the major worldwide public health issues. However, the evidence for low-latitude plateau regions is limited, where the climate is unique and diverse with a complex geography and topography. objectives: This study aimed to evaluate the effect of ambient temperature on the mortality burden of nonaccidental deaths in Yunnan Province and to further explore its spatial heterogeneity among different regions. Methods: We collected mortality and meteorological data from all 129 counties in Yunnan Province from 2014 to 2020, and 16 prefecture-level cities were analyzed as units. A distributed lagged nonlinear model was used to estimate the effect of temperature exposure on years of life lost (YLL) for nonaccidental deaths in each prefecture-level city. The attributable fraction of YLL due to ambient temperature was calculated. A multivariate meta-analysis was used to obtain an overall aggregated estimate of effects, and spatial heterogeneity among 16 prefecture-level cities was evaluated by adjusting the city-specific geographical characteristics, demographic characteristics, economic factors, and health resources factors. Results: The temperature-YLL association was nonlinear and followed slide-shaped curves in all regions. The cumulative cold and heat effect estimates along lag 0-21 days on YLL for nonaccidental deaths were 403.16 (95% empirical confidence interval [eCI] 148.14-615.18) and 247.83 (95% eCI 45.73-418.85), respectively. The attributable fraction for nonaccidental mortality due to daily mean temperature was 7.45% (95% eCI 3.73%-10.38%). Cold temperature was responsible for most of the mortality burden (4.61%, 95% eCI 1.70-7.04), whereas the burden due to heat was 2.84% (95% eCI 0.58-4.83). The vulnerable subpopulations include male individuals, people aged <75 years, people with education below junior college level, farmers, nonmarried individuals, and ethnic minorities. In the cause-specific subgroup analysis, the total attributable fraction (%) for mean temperature was 13.97% (95% eCI 6.70-14.02) for heart disease, 11.12% (95% eCI 2.52-16.82) for respiratory disease, 10.85% (95% eCI 6.70-14.02) for cardiovascular disease, and 10.13% (95% eCI 6.03-13.18) for stroke. The attributable risk of cold effect for cardiovascular disease was higher than that for respiratory disease cause of death (9.71% vs 4.54%). Furthermore, we found 48.2% heterogeneity in the effect of mean temperature on YLL after considering the inherent characteristics of the 16 prefecture-level cities, with urbanization rate accounting for the highest proportion of heterogeneity (15.7%) among urban characteristics. Conclusions: This study suggests that the cold effect dominated the total effect of temperature on mortality burden in Yunnan Province, and its effect was heterogeneous among different regions, which provides a basis for spatial planning and health policy formulation for disease prevention.

Lysophosphatidylcholine trigger myocardial injury in diabetic cardiomyopathy via the TLR4/ZNF480/AP-1/NF-kB pathway.

Background: Diabetic cardiomyopathy (DC), a frequent complication of type 2 diabetes mellitus (T2DM), is mainly associated with severe adverse outcomes. Previous research has highlighted the role of Lysophosphatidylcholine (LPC) in inducing myocardial injury; however, the specific mechanisms through which LPC mediate such injury in DC remain elusive. The existing knowledge gap underscores the need for additional clarification. Consequently, this study aimed to explore the impact and underlying mechanisms of LPC on myocardial injury in DC. Methods: A total of 55 patients diagnosed with T2DM and 62 healthy controls were involved. A combination of 16s rRNA sequencing, metabolomic analysis, transcriptomic RNA-sequencing (RNA-seq), and whole exome sequencing (WES) was performed on fecal and peripheral blood samples collected from the participants. Following this, correlation analysis was carried out, and the results were further validated through the mouse model of T2DM. Results: Four LPC variants distinguishing T2DM patients from healthy controls were identified, all of which were upregulated in T2DM patients. Specifically, Lysopc (16:0, 2 N isoform) and LPC (16:0) exhibited a positive correlation with nuclear factor kappa B subunit 2 (NFKB2) and a negative correlation with Zinc finger protein 480 (ZNF480) Furthermore, the expression levels of Toll-like receptor 4 (TLR4), c-Jun, c-Fos, and NFKB2 were upregulated in the peripheral blood of T2DM patients and in the myocardial tissue of T2DM mice, whereas ZNF480 expression level was downregulated. Lastly, myocardial injury was identified in T2DM mice. Conclusions: The results indicated that LPC could induce myocardial injury in DC through the TLR4/ZNF480/AP-1/NF-kB pathway, providing a precise target for the clinical diagnosis and treatment of DC.

A Reverse Suture Anchor Technique for Arthroscopic Medial Meniscus Root Repair.

Injuries of the posterior root of the medial meniscus can be accompanied by damage to the anterior cruciate ligament or often occur independently in cases of degenerative meniscal injury in older individuals. Anchor suture repair can achieve favorable biomechanical effects and clinical outcomes. However, anchor placement is technically challenging and requires a posterior medial approach, which increases the risk of iatrogenic injury. To address these issues, we have utilized the reverse anchor technique to repair the posterior root of the medial meniscus. This technique offers advantages such as reduced surgical time, simplified operation, and reduced risk of the "bungee effect" and iatrogenic injury.