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Polydiacetylene (PDA) liposomes have been widely applied for detection due to their distinctive optical properties. However, the liquid phase in which PDA liposomes are dispersed generates several drawbacks, for instance, instability, compromise of detection sensitivity induced by dilution, and separation of target sampling and detection, making it inconvenient for application. In this paper, various functionalized PDA liposomes for detecting target were prepared, which were also immobilized into swelling microneedles to construct a solid-phase detection system. The PDA liposomes-complexed microneedles (PDA/MNs) enable the integration of target sampling and detection in one platform. The effects of the dispersing matrix phase on the detection sensitivity of PDA liposomes were systematically investigated from both environmental and chemical perspectives. PDA/MNs exhibited higher sensitivity than their counterparts in liquid phase. PDA/MNs were optimized and validated for lead ion (Pb2+) and sialic acid (SA) detections. For Pb2+ detection, the limit of detection (LOD) of the PDA/MNs was 13.7 μM and 2.5 times lower than the liquid phase. For SA detection, the LOD of the PDA/MNs was 0.83 μM and 1.7 times lower than the liquid phase. The results suggested that such PDA/MNs were validated to provide a label-free, stable, sensitive, and convenient tool in an all-in-one manner for physiologic target detection.

Abstract The existence of flaws seriously weakens the rock strength, directly affects the crack expansion morphology, and indirectly affects the slope stability. In this study, uniaxial compression tests were carried out on double-flawed granite to investigate the effects of flaw angle on its compressive strength and crack coalescence based on DIC technology and PFC2D numerical simulation. The result indicates that the UCS values of flawed specimens at angles of 15°, 30°, 45°, and 60° are approximately 25.5–51.7% lower than that of the intact specimen. The failure strength of the double-flawed sample increases with the increase of flaw inclination angle, and the fracture morphology shifts from no expansion to split expansion. When the flaw tip strain of each flaw sample exceeded 0.6%, the stress concentration was generated at the flaw tip, and the sample began to appear macroscopic large cracks. DIC technique can well observe the crack initiation and propagation process, recording inclined shear strain bands at flaw tips, tensile strain bands in the middle of flaws, and tensile shear O-shaped strain ring in rock bridge areas. Numerical simulations using PFC2D software were carried out and showed a good agreement with the physical results. In addition, the effect of structural inclination on specimen failure strength is clearly explained by the theory of compressive damage based on the projected size of flaws. The deformation of rock mass is not a simple material deformation but is composed of material deformation and structural deformation. These experimental and numerical results enhance our understanding of crack initiation and coalescence characteristics, aiding in the analysis of rock structure stability in scenarios such as excavated underground openings, slopes, and tunneling construction, where pre-existing cracks or step-path fractures are pivotal to structural integrity.

Background Tennis, the second-largest ball game in the world, has a particularly wide audience. To date, little research has been conducted on the biomechanics of female serves. Purpose The purpose of this study was to capture the key moments by using 1,000 frames/s high-speed video analysis, to analyze the kinematics of the serving techniques of national athletes and provincial athletes, to determine the differences between the two levels of athletes, and to provide theoretical references for the improvement of scientific training level. Methods Ten female athletes were selected as participants for this study, five of whom are national athletes, and the other are provincial athletes. Three-dimensional filming techniques were employed to capture videos of the first and second serve techniques. Simi Motion was applied to obtain the 3D kinematic data. Statistical analyses were performed using IBM SPSS Statistics 27.0, and Mann–Whitney U tests were conducted to determine differences between groups. Results Significant differences in kinematics were found between national and provincial athletes. At the moment of the left knee’s minimum flexion (T2), in the first serve, national athletes had a smaller shoulder-hip vertical plane angle (−18.281 ± 6.142° vs. −25.631 ± 3.497°; p = 0.047) and a larger hip vertical plane rotation angle (−9.378 ± 4.263° vs. −0.470 ± 4.724°; p = 0.047). In the second serve, national athletes had a smaller hip horizontal plane rotation angle (−1.720 ± 4.683° vs. 24.146 ± 24.014°; p = 0.047) but a larger hip vertical plane rotation angle (−11.553 ± 1.949° vs. −0.422 ± 4.958°; p = 0.009). At the moment of impact (T4), in the second serve, national athletes’ batting position (0.296 ± 0.088 m vs. 0.446 ± 0.094 m; p = 0.047) was further back. Additionally, in the second serve, national athletes consistently had their body center of gravity further back at T2 (−0.106 ± 0.052 m vs. −0.018 ± 0.048 m; p = 0.028), T3 (0.002 ± 0.038 m vs. 0.132 ± 0.039 m; p = 0.009), and T4 (0.073 ± 0.050 m vs. 0.217 ± 0.034 m; p = 0.009). Conclusions The results of this study indicated several significant kinematic differences between national and provincial athletes, these variations were noted in the shoulder, hip, and body center of gravity. In summary, for the overall first and second serves, it is recommended that national athletes increase the horizontal plane angle of the shoulders and hips at T2, whereas provincial athletes decrease the horizontal plane angle of the shoulder–hip. In addition, provincial athletes need to increase the vertical plane angle of the hip joint, so that the top of the hip can be increased more, and provincial athletes need to be careful not to have the center of gravity too far in front of the body at T2, T3, and T4, so that it can hit the ball at a higher position to increase the swing speed.

Objectives This research aims to explore the correlation between ABO blood groups and neoplasms in the head and neck region, specifically investigating the susceptibility of different blood groups to tumours.Design Systematic review and meta-analysis.Data sources CNKI, WANFANG DATA, PubMed, Web of Science and Embase databases were systematically searched from inception to January 2024.Eligibility criteria All studies of ABO blood type and head and neck tumours will be included in this study.Data extraction and synthesis A systematic literature review was performed using digital platforms on CNKI, WANFANG DATA, PubMed, Web of Science and Embase databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for meta-analysis. Two authors independently extracted the data and assessed the quality of included studies. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Comparisons were made between blood types A, B, AB and their combined group versus O, along with subgroup analyses. Systematic analysis was performed by using Review Manager V.5.4 and Stata V.18 statistical software.Results 30 articles were included, involving 737 506 subjects, among which 21 382 were patients with head and neck tumours. The overall analysis indicated a significant association between type AB blood (OR 0.762, 95% CI 0.637 to 0.910) and a reduced risk of head and neck tumours. In the Caucasoid race, type A blood is significantly linked to an elevated likelihood of head and neck tumours (OR 1.353, 95% CI 1.076 to 1.702), while in the Mongoloid race, type AB blood is significantly linked to a reduced likelihood of developing tumours in the head and neck area (OR= 0.732, 95% CI 0.588 to 0.910). No significant associations were found in the subgroup analysis by gender. Regarding different types of cancer, type A blood is significantly associated with an increased risk of salivary gland tumours (OR 1.338, 95% CI 1.075 to 1.665), and type AB blood is significantly linked to a lower likelihood of nasopharyngeal carcinoma (OR 0.590, 95% CI 0.429 to 0.812).Conclusion A correlation exists between ABO blood groups and tumours in the head and neck region. However, the link between blood type and head and neck tumours requires further confirmation through more prospective studies.PROSPERO registration number CRD42024510176.

The balanced gut microbiota in intestinal mucus layer plays an instrumental role in the health of the host. However, the mechanisms by which the host regulates microbial communities in the mucus layer remain largely unknown. Here, we discovered that the host regulates bacterial colonization in the gut mucus layer by producing a protein called Chitinase 3-like protein 1 (Chi3l1). Intestinal epithelial cells are stimulated by the gut microbiota to express Chi3l1. Once expressed, Chi3l1 is secreted into the mucus layer where it interacts with the gut microbiota, specifically through a component of bacterial cell walls called peptidoglycan. This interaction between Chi3l1 and bacteria is beneficial for the colonization of bacteria in the mucus, particularly for Gram-positive bacteria like Lactobacillus. Moreover, a deficiency of Chi3l1 leads to an imbalance in the gut microbiota, which exacerbates colitis induced by dextran sodium sulfate. By performing fecal microbiota transplantation from Villin-cre mice or replenishing Lactobacillus in IEC∆Chil1 mice, we were able to restore their colitis to the same level as that of Villin-cre mice. In summary, this study shows a ‘scaffold model’ for microbiota homeostasis by interaction between intestinal Chi3l1 and bacteria cell wall interaction, and it also highlights that an unbalanced gut microbiota in the intestinal mucus contributes to the development of colitis.

Abstract Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01–1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China.

Abstract Secondary lung injury after SCI is a major cause of patient mortality, with apoptosis playing a key role. This study aimed to explore the impact of treadmill training and miR145-5p on the MAPK/Erk signaling pathway and apoptosis in rats with complete SCI. SD rats were used to establish T10 segmental complete SCI models and underwent treadmill training 3, 7, or 14 days postinjury. Various techniques including arterial blood gas analysis, lung wet/dry weight ratio, HE staining, immunofluorescence staining, immunohistochemical staining, qRT-PCR, and Western blotting were employed to assess alterations in lung function and the expression levels of crucial apoptosis-related factors. In order to elucidate the specific mechanism, the impact of miR145-5p on the MAPK/Erk pathway and its role in apoptosis in lung cells were confirmed through miR145-5p overexpression and knockdown experiments. Following spinal cord injury (SCI), an increase in apoptosis, activation of the MAPK/Erk pathway, and impairment of lung function were observed in SCI rats. Conversely, treadmill training resulted in a reduction in alveolar cell apoptosis, suppression of the MAPK/Erk pathway, and enhancement of lung function. The gene MAP3K3 was identified as a target of miR145-5p. The influence of miR145-5p on the MAPK/Erk pathway and its impact on apoptosis in alveolar cells were confirmed through the manipulation of miR145-5p expression levels. The upregulation of miR145-5p in spinal cord injury (SCI) rats led to a reduction in MAP3K3 protein expression within lung tissues, thereby inhibiting the MAPK/Erk signaling pathway and decreasing apoptosis. Contrarily, rats with miR145-5p knockdown undergoing treadmill training exhibited an increase in miR145-5p expression levels, resulting in the inhibition of MAP3K3 protein expression in lung tissues, suppression of the MAPK/Erk pathway, and mitigation of lung cell apoptosis. Ultimately, the findings suggest that treadmill training may attenuate apoptosis in lung cells post-spinal cord injury by modulating the MAP3K3 protein through miR145-5p to regulate the MAPK/Erk signaling pathway.

Abstract Background Laminin subunit gamma-1 (LAMC1) is a major extracellular matrix molecule involved in the tumor microenvironment. Knowledge of the biological features and clinical relevance of LAMC1 in cancers remains limited. Methods We conducted comprehensive bioinformatics analysis of LAMC1 gene expression and clinical relevance in pan-cancer datasets of public databases and validated LAMC1 expression in glioma tissues and cell lines. The association and regulatory mechanism between hypoxia inducible factor-1α (HIF-1α) and LAMC1 expression were explored. Results LAMC1 expression in most cancers in The Cancer Genome Atlas (TCGA) including glioma was significantly higher than that in normal tissues, which had a poor prognosis and were related to various clinicopathological features. Data from the Chinese Glioma Genome Atlas also showed high expression of LAMC1 in glioma associated with poor prognoses. In clinical glioma tissues, LAMC1 protein was highly expressed and correlated to poor overall survival. LAMC1 knockdown in Hs683 glioma cells attenuated cell proliferation, migration, and invasion, while overexpression of LAMC1 in U251 cells leads to the opposite trend. Most TCGA solid cancers including glioma showed enhancement of HIF-1α expression. High HIF-1α expression leads to adverse prognosis in gliomas, besides, HIF-1α expression was positively related to LAMC1. Mechanistically, HIF-1α directly upregulated LAMC1 promotor activity. Hypoxia (2% O2)-treated Hs683 and U251 cells exhibited upregulated HIF-1α and LAMC1 expression, which was significantly attenuated by HIF-1α inhibitor YC-1 and accompanied by attenuated cell proliferation and invasion. Conclusions High expression of LAMC1 in some solid tumors including gliomas suggests a poor prognosis. The hypoxic microenvironment in gliomas activates the HIF-1α/LAMC1 signaling, thereby promoting tumor progression. Targeted intervention on the HIF-1α/LAMC1 signaling attenuates cell growth and invasion, suggesting a new strategy for glioma treatment.

Abstract The spatial response mechanism of hydrology and water quality of large river-connected lakes is very complicated. In this study, we developed a spatial response analysis method that couples wavelet correlation analysis (WTC) with self-organizing maps (SOM), revealing the spatial response and variation of water level and water quality in Poyang Lake, China's largest river-connected lake, over the past decade. The results show that: (1) there was significant spatial heterogeneity in water level and quality during the dry seasons (2010–2018) compared to other hydrological stages. (2) We identified a more pronounced difference in response of water level and quality between northern and southern parts of Poyang Lake. As the distance increases from the northern lake outlet, the impact of rising water levels on water quality deterioration intensified during the dry seasons. (3) The complex spatial heterogeneity of water level and quality response in the dry seasons is primarily influenced by water level fluctuations from the northern region and the cumulative pollutant entering the lake from the south, which particularly leads to the reversal of the response in the central area of Poyang Lake. The results of this study can contribute to scientific decision-making regarding water environment zoning management in large river-connected lakes amidst complex environment conditions.

Abstract Improving drug sensitivity is an important strategy in chemotherapy of cancer and accumulating evidence indicates that miRNAs are involved in the regulation of drug sensitivity, but the specific mechanism is still unclear. Our previous study has found that miR-296-5p was significantly downregulated in nasopharyngeal carcinoma (NPC). Here, we aim to explore whether miR-296-5p is involved in regulating cisplatin sensitivity in NPC by regulating STAT3/KLF4 signaling axis. The cell proliferation and clonogenic capacity of NPC cells were evaluated by CCK8 Assay and plate colony assay, respectively. The Annexin V-FITC staining kit was used to determine and quantify the apoptotic cells using flow cytometry. The drug efflux ability of NPC cells were determined by Rhodamine 123 efflux experiment. The expression of miR-296-5p, apoptosis-related genes and protein in NPC cell lines were detected by qPCR and Western blot, respectively. Animal study was used to evaluate the sensitivity of NPC cells to DDP treatment in vivo. Our results showed that elevated miR-296-5p expression obviously promoted the sensitivity of NPC cells to DDP by inhibiting cell proliferation and clonogenic capacity, and inducing apoptosis. In addition, we found that miR-296-5p inhibited the expression of STAT3 and KLF4 in NPC cells, while overexpression of exogenous STAT3 reversed miR-296-5p-mediated enhancement in cell death of DDP-treated NPC cells. In vivo studies further confirmed that miR-296-5p promotes the sensitivity of NPC cells to DDP treatment. miRNA-296-5p enhances the drug sensitivity of nasopharyngeal carcinoma cells to cisplatin via STAT3/KLF4 signaling pathway.

Abstract The clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.

Abstract Background As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. Methods Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. Results Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12–74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92–1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. Conclusion The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

Objective The relationship between vitiligo and cardiovascular diseases remains controversial. This study aimed to systematically review the evidence comparing cardiovascular disease risk factors between patients with vitiligo and controls and to perform a meta-analysis of the results.Data sources A comprehensive database search was performed for all studies in PubMed, EMBASE, and Cochrane Central Register databases from inception to November, 2023. The main keywords used were vitiligo, hypertension, diabetes, hyperlipidemia, metabolic syndrome, obesity, smoking, alcohol consumption, C-reactive protein, and homocysteine.Study selection Only observational studies and no randomized controlled trials were included. Of the 1269 studies initially selected, the full texts of 108 were assessed for eligibility, and 74 were ultimately included in the analysis.Data extraction and synthesis Three reviewers independently extracted the following data: study design, number and characteristics of participants, inclusion indicators, and disease duration. A meta-analysis of the single-group rates was performed for the diabetes, hypertension, hyperlipidemia, and obesity groups. Random-effects or fixed-effects models were used to calculate the sample-size weighted averages for the indicators included in the studies.Main outcomes and measures The primary outcomes were co-morbidity analysis and co-morbidity rates of vitiligo with metabolic syndrome, obesity, hyperlipidemia, hypertension, and diabetes mellitus. Secondary outcomes were factors associated with vitiligo and cardiovascular disease.Results This meta-analysis concluded that comorbidities in patients with vitiligo included metabolic syndrome, diabetes, obesity, hyperlipidemia, and hypertension, with comorbidity rates of 28.3%, 6.0%, 38.5%, 43.0%, and 15.8%, respectively. Simultaneously, we showed that the vitiligo group differed significantly from the control group in the following aspects: fasting blood glucose, insulin, systolic and diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, homocysteine, C-reactive protein, smoking, and alcohol consumption. However, no significant differences were observed between the vitiligo and control groups in terms of waist circumference, body mass index, or phospholipid levels.Limitations The vast majority of the studies were from Eastern countries; therefore, extrapolation of these results to Western populations is questionable. The significant heterogeneity may be due to different protocols, doses, durations, center settings, population registries, etc., which severely compromise the validity of the results.Conclusion This study summarized not only the factors associated with, but also those not associated with, cardiovascular disease in patients with vitiligo. This study provides a foundation for the prevention and treatment of cardiovascular disease in patients with vitiligo.

Background Inhaler concordance and the peak inspiratory flow rate (PIFR) are important determinants of treatment effects in patients with chronic airway diseases. Adequate PIFR is required for driving aerosol medication into the lower respiratory tract. However, the relationship between them has not been discussed previously. This study aimed to describe the characteristics of inhaler concordance and PIFR in Chinese patients with chronic airway diseases and discuss the associated variables and the relationship between them.Methods In this single-centre, observational study, a total of 680 patients with chronic airway diseases were enrolled from July 2021 to April 2023. We collected data on the socio-demographic and clinical variables of inhaler concordance using the test of adherence to inhalers (TAI) and PIFR. Multivariate logistic regression was conducted to examine variables related to inhaler concordance and PIFR.Results A total of 49.4% of patients had low concordance. Patients with chronic obstructive pulmonary disease (COPD) were more concordant than patients with asthma (mean TAI score: 43.60 vs 41.20; p

Introduction HIV infection is one of the complex aetiologies of non-Hodgkin’s lymphoma (NHL). However, the contribution of HIV to burden of NHL across time and region has not yet been comprehensively reported and quantified. Thus, this study aims to evaluate the relative risk of NHL in individuals with HIV infection compared with those without by performing a comprehensive meta-analysis. Additionally, we intend to further estimate quantitatively the degree of HIV contributing to burden of NHL using population attributable fraction (PAF) modelling analysis.Methods and analysis This study will screen a mass of records searched from four electronic databases (PubMed, Embase, Cochrane Library and Web of Science). The main outcomes are specific effect values and corresponding 95% CIs for NHL among population with HIV infection compared with those without to quantify the association between HIV infection and NHL. After quality assessment and data extraction, we will undertake a meta-analysis to calculate the pooled risk ratio (RR). Furthermore, PAF calculation based on pooled RR combines with number of age-specific disability-adjusted life year (DALY) and HIV prevalence data (aged ≥15 years old) from 1990 to 2019, at global, regional and country levels. We will calculate the PAF, HIV-associated DALY number and age-standardised rate to quantify the burden of HIV-associated NHL.Ethics and dissemination This study is based on published articles; thus, the ethic approval is not essential. In addition, we intend to publish the results on peer-reviewed journals for more discussion. We believe that research on estimating global burden of NHL can provide valuable insights for developing targeted prevention and control strategies, thereby achieving significant benefits.PROSPERO registration number CRD 42023404150.

Abstract mRNA vaccines are becoming a feasible alternative for treating cancer. To develop mRNA vaccines against LUAD, potential antigens were identified and LUAD ferroptosis subtypes distinguished for selecting appropriate patients. The genome expression omnibus, cancer genome atlas (TCGA) and FerrDB were used to collect gene expression profiles, clinical information, and the genes involved in ferroptosis, respectively. cBioPortal was used to visualize and compare genetic alterations, GEPIA2 to calculate prognostic factors of the selected antigens, and TIMER to visualize the relationship between potential antigens and tumor immune cell infiltration. Consensus clustering analysis was utilized to identify ferroptosis subtypes and their prognostic value assessed by Log-rank and cox regression tests. The modules of ferroptosis-related gene screening were conducted by weight gene co-expression network analysis. The LUAD ferroptosis landscape was visualized through dimensionality reduction and graph learning. Six tumor antigens had obvious LUAD-mutations, positively correlated with different antigen-presenting cells, and might induce tumor cell ferroptosis. LUAD patients were stratified into three ferroptosis subtypes (FS1, FS2, and FS3) according to diverse molecular, cellular, and clinical characteristics. FS3 showed the highest tumor mutation burden and the most somatic mutations, deemed potential indicators of mRNA vaccine effectiveness. Moreover, different ferroptosis subtypes expressed distinct immune checkpoints and immunogenic cell death modulators. AGPS, NRAS, MTDH, PANX1, NOX4, and PPARD are potentially suitable for mRNA vaccinations against LUAD, specifically in patients with FS3 tumors. This study defines vaccination candidates and establishes a theoretical basis for LUAD mRNA vaccinations.

Abstract Background Evolutionary models of breast cancer progression differ on the extent to which metastatic potential is pre-encoded within primary tumors. Although metastatic recurrences often harbor putative driver mutations that are not detected in their antecedent primary tumor using standard sequencing technologies, whether these mutations were acquired before or after dissemination remains unclear. Methods To ascertain whether putative metastatic driver mutations initially deemed specific to the metastasis by whole exome sequencing were, in actuality, present within rare ancestral subclones of the primary tumors from which they arose, we employed error-controlled ultra-deep sequencing (UDS-UMI) coupled with FFPE artifact mitigation by uracil-DNA glycosylase (UDG) to assess the presence of 132 “metastasis-specific” mutations within antecedent primary tumors from 21 patients. Maximum mutation detection sensitivity was ~1% of primary tumor cells. A conceptual framework was developed to estimate relative likelihoods of alternative models of mutation acquisition. Results The ancestral primary tumor subclone responsible for seeding the metastasis was identified in 29% of patients, implicating several putative drivers in metastatic seeding including LRP5 A65V and PEAK1 K140Q. Despite this, 93% of metastasis-specific mutations in putative metastatic driver genes remained undetected within primary tumors, as did 96% of metastasis-specific mutations in known breast cancer drivers, including ERRB2 V777L, ESR1 D538G, and AKT1 D323H. Strikingly, even in those cases in which the rare ancestral subclone was identified, 87% of metastasis-specific putative driver mutations remained undetected. Modeling indicated that the sequential acquisition of multiple metastasis-specific driver or passenger mutations within the same rare subclonal lineage of the primary tumor was highly improbable. Conclusions Our results strongly suggest that metastatic driver mutations are sequentially acquired and selected within the same clonal lineage both before, but more commonly after, dissemination from the primary tumor, and that these mutations are biologically consequential. Despite inherent limitations in sampling archival primary tumors, our findings indicate that tumor cells in most patients continue to undergo clinically relevant genomic evolution after their dissemination from the primary tumor. This provides further evidence that metastatic recurrence is a multi-step, mutation-driven process that extends beyond primary tumor dissemination and underscores the importance of longitudinal tumor assessment to help guide clinical decisions.

Abstract Background The need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues. However, the effects and mechanisms of senescent cells on re-epithelialization and collagen deposition in radiation-induced skin injury have not been fully elucidated. Results Here, we identified a role for a population of senescent cells expressing p16 in promoting re-epithelialization and collagen deposition in radiation-induced skin injury. Targeted ablation of p16+ senescent cells or treatment with Senolytics resulted in the disruption of collagen structure and the retardation of epidermal coverage. By analyzing a publicly available single-cell sequencing dataset, we identified fibroblasts as a major contributor to the promotion of re-epithelialization and collagen deposition in senescent cells. Notably, our analysis of publicly available transcriptome sequencing data highlighted IL-33 as a key senescence-associated secretory phenotype produced by senescent fibroblasts. Neutralizing IL-33 significantly impedes the healing process. Finally, we found that the effect of IL-33 was partly due to the modulation of macrophage polarization. Conclusions In conclusion, our data suggested that senescent fibroblasts accumulated in radiation-induced skin injury sites participated in wound healing mainly by secreting IL-33. This secretion regulated the local immune microenvironment and macrophage polarization, thus emphasizing the importance of precise regulation of senescent cells in a phased manner. Graphical Abstract

Abstract Motivated by the effect of symmetry breaking in cuprates superconductors YBa $$_2$$ 2 Cu $$_3$$ 3 O $$_{7-\delta }$$ 7 - δ , we employ the renormalized mean-field theory to study the presence of uniform superconducting and charge-ordered states in two anisotropic t–J–U models, either with hopping strength anisotropy or antiferromagnetic interaction anisotropy. In the case of uniform superconducting state, compared with the isotropic t–J–U model with only $$d_{x^2-y^2}$$ d x 2 - y 2 -wave superconducting state, there is an additional s-wave superconducting state in the model with hopping strength anisotropy. Meanwhile, the hopping anisotropy may enhance the critical Coulomb interaction $$U_c$$ U c at the Mott insulator to the Gossamer superconductor transition point, and strong hopping anisotropy may weaken the superconducting state. In the case of a charge-ordered state, hopping anisotropy may suppress the amplitude of the charge density waves and pair density waves, which originate from local Coulomb interactions. These results indicate that the effects of hopping anisotropy and local Coulomb interactions are competitive. Moreover, the antiferromagnetic interaction anisotropy only weakly suppresses the superconducting gap and density wave amplitude. Our results show that the t–J–U model with hopping anisotropy is qualitatively consistent with experimental superconducting pair symmetry and charge density waves in the YBa $$_2$$ 2 Cu $$_3$$ 3 O $$_{7-\delta }$$ 7 - δ system.

AbstractInflammatory markers have a wide range of predictive values in the prognosis of non-small lung cancer (NSCLC). Poor nutritional status usually means a poor prognosis in patients with NSCLC, which is widely recognized by oncologists and nutritionists. Serum albumin has a certain value in evaluating the prognosis of patients. Several inflammatory albumin-related markers have been proposed, but they have not been widely used in predicting the prognosis of NSCLC in clinical practice. We aim to systematically review the published clinical evidence of albumin-related inflammatory markers in predicting the prognosis of NSCLC and to describe their progress and value. The results showed that the markers included in the review could be prognostic indicators in patients with NSCLC. However, we found that the cut-off value of albumin-related inflammatory markers with quantitative nature was very chaotic and needed to be defined by recognized standards. We summarized and compared the advantages and disadvantages of these markers, but a prospective cohort study with long-term follow-up after adjustment for important confounders is still necessary. Whether the results and conclusions could be directly applied in clinical practice needs to be identified and evaluated. There is an urgent need to classify and standardize the albumin-related inflammatory markers that play an important role in the prognosis of NSCLC, which is the key to ensuring the transformation from clinical study to clinical application.

AbstractBackground The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients.Patients and methods This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data.Results We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients.Conclusion Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients.KEY MESSAGESOver half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world.The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.

AbstractBackground We discovered that vitiligo was associated with sexual dysfunction in clinical diagnosis and treatment; however, no further analysis had been performed due to a lack of data.Objective This study aimed to clarify the relationship between vitiligo and sexual dysfunction.Methods We searched six databases (PubMed, Embase, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang Data Knowledge Service Platform) for nearly 40 years.Results According to the search strategy, 91 relevant studies were retrieved, of which 4 were included in the analysis. The Arizona Sexual Experience Scale (ASEX) score (mean difference [MD] 4.96, 95% confidence interval [CI] 2.78–7.13, p

Objectives Protein C (PC) is an anticoagulant that is encoded by the PROC gene. Validation for the function of PC was carried out in mouse models. Methods In this study, autosomal recessive PC deficiency (PCD) was selected as the target, and the specific mutation site was chromosome 2 2q13-q14, PROC c.1198G>A (p.Gly400Ser) which targets G399S (GGT to AGC) in mouse models. To investigate the role of hereditary PC in mice models, we used CRISPR/Cas9 gene editing technology to create a mouse model with a genetic PCD mutation. Results The two F0 generation positive mice produced using the CRISPR/Cas9 gene editing technique were chimeras, and the mice in F1 and F2 generations were heterozygous. There was no phenotype of spontaneous bleeding or thrombosis in the heterozygous mice, but some of them were blind. Blood routine results showed no significant difference between the heterozygous mice and wild-type mice (P > 0.05). Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged in the heterozygous mice, while the level of fibrinogen content (FIB) decreased, suggesting secondary consumptive coagulation disease. The protein C activity of heterozygous mice was significantly lower than that of wild-type mice (P 0.05). H&E staining showed steatosis and hydrodegeneration in the liver of heterozygous mice. Necrosis and exfoliated epithelial cells could be observed in renal tubule lumen, forming cell or granular tubules. Hemosiderin deposition was found in the spleen along with splenic hemorrhage. Immunohistochemistry demonstrated significant fibrin deposition in the liver, spleen, and kidney of heterozygous mice. Conclusion In this study, heterozygotes of the mouse model with a PC mutation were obtained. The function of PC was then validated in a mouse model through genotype, phenotype, and PC function analysis.

Targeting tumor angiogenesis is an important approach in advanced tumor therapy. Here we investigated the effect of the suppressor of variegation 3–9 homolog 1 (SUV39H1) on tumor angiogenesis in oral squamous cell carcinoma (OSCC). The GEPIA database was used to analyze the expression of SUV39H1 in various cancer tissues. The expression of SUV39H1 in OSCC was detected by immunohistochemistry, and the correlation between SUV39H1 and Notch1 and microvascular density (MVD) was analyzed. The effect of SUV39H1 inhibition on OSCC was investigated in vivo by chaetocin treatment. The migration and tube formation of vascular endothelial cells by conditioned culture-medium of different treatments of oral squamous cell cells were measured. The transcriptional level of SUV39H1 is elevated in various cancer tissues. The transcription level of SUV39H1 in head and neck squamous cell carcinoma was significantly higher than that in control. Immunohistochemistry result showed increased SUV39H1 expression in OSCC, which was significantly correlated with T staging. The expression of SUV39H1 was significantly correlated with Notch1 and CD31. In vivo experiment chaetocin treatment significantly inhibit the growth of tumor, and reduce SUV39H1, Notch1, CD31 expression. The decreased expression of SUV39H1 in OSCC cells lead to the decreased expression of Notch1 and VEGF proteins, as well as the decreased migration and tube formation ability of vascular endothelial cells. Inhibition of Notch1 further enhance this effect. Our results suggest inhibition of SUV39H1 may affect angiogenesis by regulating Notch1 expression. This study provides a foundation for SUV39H1 as a potential therapeutic target for OSCC.

Abstract To further evaluate the causal relationships between inflammatory cytokines and migraine, we conducted a bidirectional, two-sample Mendelian randomization (MR) analysis using genetic data from publicly available genome-wide association studies (GWAS). We used several MR methods, including random-effect inverse-variance weighting (IVW), weighted median, MR-Egger, to test the causal relationships. Sensitivity analyses were also conducted to evaluate the robustness of the results. The results showed that hepatocyte growth factor (HGF) was positively associated with the risk of migraine (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001–1.008; P = 0.022). In addition, Interleukin-2 (IL-2) was considered a downstream consequence of migraine (OR, 0.012; 95% CI, 0.000–0.0929; P = 0.046). These findings suggest that HGF may be a factor associated with the etiology of migraine, while IL-2 is more likely to be involved in the downstream development of migraine.

Abstract The pandemic of COVID-19 was a major public health events and had a deeply impact on the healthcare acquired by patients with inflammatory bowel disease (IBD). The purpose of this study was to evaluate the long-term impacts on healthcare service in Chinese IBD patients under the dynamic zero-COVID strategy. The study was performed in the Inflammatory Bowel Disease Quality of Care Centers in mainland China in 2021. The data about the healthcare was collected by a 44-item questionnaire. Totally 463 were from ulcerative colitis (UC) patients and 538 from Crohn’s disease (CD) patients were included in the study. The pandemic impacted 37.5% patients on their treatment, and the biggest problem was unable to follow up timely (77.9%). There was a significant increase in healthcare costs in CD (P

Abstract. Background:. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 proposed a new classification that reclassified many chronic obstructive pulmonary disease (COPD) patients from group D to B. However, there is a paucity of data related to the comparison between reclassified and non-reclassified COPD patients in terms of long-term prognosis. This study aimed to investigate long-term outcomes of them and determine whether the GOLD 2017 revision improved the assessment of COPD patients. Methods:. This observational, multicenter, prospective study recruited outpatients at 12 tertiary hospitals in China from November 2016 to February 2018 and followed them up until February 2022. All enrolled patients were classified into groups A to D based on GOLD 2017, and the subjects in group B included patients reclassified from group D to B (group DB) and those remaining in group B (group BB). Incidence rates and hazard ratios (HRs) were calculated for the exacerbation of COPD and hospitalization in each group. Results:. We included and followed up 845 patients. During the first year of follow-up, the GOLD 2017 classification had a better discrimination ability for different risks of COPD exacerbation and hospitalization than GOLD 2013. Group DB was associated with a higher risk of moderate-to-severe exacerbation (HR = 1.88, 95% confidence interval [CI] = 1.37–2.59, P

Abstract This study used a Mendelian randomization (MR) approach to investigate the causal relationship between genetically predicted endometriosis (EMS) and breast cancer risk. A total of 122,977 cases and 105,974 controls were included in the analysis, with gene-level summary data obtained from the Breast Cancer Association Consortium (BCAC). An inverse variance-weighting approach was applied to assess the causal relationship between EMS and breast cancer risk, and weighted median and MR-Egger regression methods were used to evaluate pleiotropy. Results showed a causal relationship between EMS and a decreased risk of overall breast cancer (odds ratio [OR] 0.95; 95% CI 0.90–0.99, p = 0.02). Furthermore, EMS was associated with a lower risk for estrogen receptor (ER)-positive breast cancer in a subgroup analysis based on immunohistochemistry type (OR 0.91; 95% CI 0.86–0.97, p = 0.005). However, there was no causal association between ER-negative breast cancer and survival (OR 1.00; 95% CI 0.94–1.06, p = 0.89). Pleiotropy was not observed. These findings provide evidence of a relationship between EMS and reduced breast cancer risk in invasive breast cancer overall and specific tissue types, and support the results of a previous observational study. Further research is needed to elucidate the mechanisms underlying this association.

Abstract Nemonoxacin is a novel non-fluorinated quinolone with strong antibacterial efficacy, but data of its effect on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is rare. This study was conducted to compare the efficacy of oral nemonoxacin with moxifloxacin in AECOPD outpatients. In this retrospective observational study, a total of 101 AECOPD outpatients initially treated with nemonoxacin or moxifloxacin from July 2021 to March 2022 were enrolled. We collected COPD assessment test (CAT), Transition Dyspnea Indices (TDI) scores, and exacerbations information during 24 weeks follow-up from the electronic medical records. Kaplan–Meier curve was used to analyze the time to the next moderate/severe exacerbation. Compared to the moxifloxacin group, changes in CAT scores and TDI scores were significantly higher in the nemonoxacin group, and the nemonoxacin group also had a greater probability to reach the minimal clinically important difference of CAT (71.40% vs. 97.80%, p

Abstract Background Exosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions between tumor cells and other cell populations in the tumor microenvironment have attracted most attention, little is known about the significance of exosomes in mediating the interaction between non-stemness cancer cells and cancer stem cells during cancer progression. Methods The structure, sequence and downstream target miRNAs of lncRNA Mir100hg were predicted by online web resources. The bioinformatics prediction results were validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing and mouse tail vein model of pulmonary metastasis. A complex regulatory network of "cancer stem cells-exosomal lncRNA-non-stem cancer cells" was constructed. Results This study demonstrates firstly that lncRNA Mir100hg is upregulated in lung cancer stem cell LLC-SD (Lung cancer stem cells) and can be delivered to non-stemness cancer cells LLC (Lewis lung cancer cells) via exosomes. In LLC, Mir100hg targets miR-15a-5p and miR-31-5p which leads to the increase of the global glycolytic activity of lung cancer cells and consequently, the enhancement of their metastatic capability. Conclusion We delineated a complex regulatory network that utilized by cancer stem cells to transfer their high metastatic activity to the low-metastatic non-stemness cancer cells through exosomal Mir100hg, thereby providing new mechanistic insights into the communication between two heterogeneous tumor cells. Video Abstract

Abstract Sorafenib therapy improves overall survival (OS) in patients with FLT3 internal tandem duplication (ITD) acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation. We explored the efficacy of sorafenib therapy in this population with different concomitant genetic patterns. In this multi-center, cohort study, we enrolled patients with FLT3-ITD AML undergoing allogenic hematopoietic cell transplantation. Patients with sorafenib maintenance post-transplantation for at least four weeks were allocated to the sorafenib group, and otherwise to the control group. Endpoints were OS, disease-free survival, and relapse for the whole cohort and OS for genetic pattern subgroups. Among 613 patients enrolled, 275 were in the sorafenib and 338 the control group. Median follow-up was 36.5 (interquartile range (IQR), 25.2–44.7) months post-transplantation. The 3-year OS post-transplantation was 79.6% (95% confidential interval (CI) 74.8%–84.6%) and 65.2% (95% CI 60.3%–70.6%) (Hazard ratio (HR) 0.50, 95% CI 0.37–0.69; P

Abstract Lung cancer ranks as one of the top malignancies and the leading cause of cancer death in both males and females in the US. Using a cancer database covering the entire population, this study was to determine the gender disparities in lung cancer incidence during 2001–2019. Cancer patients were obtained from the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology and End Results (SEER) database. The SEER*Stat software was applied to calculate the age-adjusted incidence rates (AAIR). Temporal changes in lung cancer incidence were analyzed by the Joinpoint software. A total of 4,086,432 patients (53.3% of males) were diagnosed with lung cancer. Among them, 52.1% were 70 years or older, 82.7% non-Hispanic white, 39.7% from the South, and 72.6% non-small cell lung cancer (NSCLC). The AAIR of lung cancer continuously reduced from 91.0 per 100000 to 59.2 in males during the study period, while it increased from 55.0 in 2001 to 56.8 in 2006 in females, then decreased to 48.1 in 2019. The female to male incidence rate ratio of lung cancer continuously increased from 2001 to 2019. Gender disparities were observed among age groups, races, and histological types. In those aged 0–54 years, females had higher overall incidence rates of lung cancer than males in recent years, which was observed in all races (except non-Hispanic black), all regions, and adenocarcinoma and small cell (but not squamous cell). Non-Hispanic black females aged 0–54 years had a faster decline rate than males since 2013. API females demonstrated an increased trend during the study period. Lung cancer incidence continues to decrease with gender disparities among age groups, races, regions, and histological types. Continuous anti-smoking programs plus reduction of related risk factors are necessary to lower lung cancer incidence further.

Abstract The disordered expression of ZNF143 is closely related to the malignant progression of tumours. However, the basic control mechanism of ZNF143 in glioma has not yet been clarified. Therefore, we tried to find a new pathway to illustrate the function of ZNF143 in glioma. To explore the function of KPNA2 in the development of glioma, we used survival analysis by the Kaplan‒Meier method to assess the overall survival (OS) of patients with low and high KPNA2 expression in the TCGA and CGGA cohorts. Western blotting assays and RT‒PCR assays were utilized to determine the expression level of KPNA2 in glioma cells. The interaction between ZNF143 and KPNA2 was confirmed by ChIP assays. Proliferation was assessed by CCK-8 assays, and migration was evaluated by wound healing and Transwell assays. Apoptosis was determined by flow cytometry, and the expression level of YAP/TAZ was visualized using an immunofluorescence assay. The expression levels of LATS1, LATS2, YAP1, and p-YAP1 were determined. Patients with low KPNA2 expression showed a better prognosis than those with high KPNA2 expression. KPNA2 was found to be upregulated in human glioma cells. ZNF143 can bind to the promoter region of KPNA2. Downregulation of ZNF143 and KPNA2 can activate the Hippo signalling pathway and reduce YAP/TAZ expression in human glioma cells, thus inducing apoptosis of human glioma cells and weakening their proliferation, migration and invasion. In conclusion, ZNF143 mediates the Hippo/YAP signalling pathway and inhibits the growth and migration of glioma cells by regulating KPNA2.

The single-nucleotide polymorphisms of genes related to DNA damage repair and inflammasomes and mutated gene expression in coal workers' pneumoconiosis (CWP) were analysed to identify the risk factors of CWP and potential biomarkers for early warning and diagnosis. Further, mutated gene pathways were analysed based on proteome and metabolome. Han Chinese male subjects were randomly selected and divided into 4 or 5 groups according to the process of CWP. MassARRAY was used to sequence single-nucleotide polymorphism genotypes. Mutated gene expression in plasma was tested using enzyme-linked immunosorbent assay (ELISA). Odds ratios (ORs) and receiver operating characteristic curves (ROC) were calculated. The serum different proteins and metabolites were identified by Ultra Performance Liquid Chromatography Quadrupole time of flight/Mass Spectrum (UPLC-Q-TOF/MS) and analysed using bioinformation software. As CWP progressed, the CC and CA genotypes of ERCC1 rs3212986 decreased and increased significantly, respectively. AA (OR = 3.016) and CA (OR = 2.130) genotypes were identified as risk factors for stage II. ERCC1 significantly decreased in processing of CWP. The cutoff value of ERCC1 was 5.265 pg/ml, with a sensitivity of 90.0% and specificity of 86.7%. ERCC1 had an indirect interaction with activator protein-1 and insulin and its pathways were mainly made with molecules related to lipid metabolism and actin dynamics. ERCC1 is a candidate biomarker for detection and precise intervention in CWP. If it reaches the threshold, workers will change other jobs in time and will not develop and diagnose as pneumoconiosis and will help the employers spend less money. Meanwhile, the signal molecules of ERCC1 pathway could be as a candidate target for drug discovery.

ObjectiveThis study aims to examine the validity of the MFS by analyzing the electronic medical records on fall risk in obstetrics and gynecology wards and determine the optimal cut-off score of the Morse Fall Scale.DesignA retrospective survey.MethodsThe research was conducted in an Obstetrics and Gynecology Hospital and a general hospital. The sample included 136 fall inpatients and 120 no-fall inpatients recruited from January 1st, 2020, to July 10th, 2022. The Morse Fall Scale was analyzed using the gold standard of patients who fell while hospitalized, assessing the area under the Receiver Operating Characteristic curve, sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and Kappa.ResultsAt cut-off scores of 40, 45,50, and 55, the area under the Receiver Operating Characteristic curve was 0.772, 0.761, 0.749, and 0.763, respectively. The Youden index was 0.543, 0.521, 0.498, and 0.525, while Kappa values were 0.540, 0.518, 0.490, and 0.515. Sensitivity was 0.735, 0.713, 0.640, and 0.625; specificity was 0.808, 0.808, 0.858, and 0.900. The positive predictive values were 0.813, 0.808, 0.837, and 0.876, and the negative predictive values were 0.729, 0.713, 0.678, and 0.679. Accuracy were 0.770, 0.758, 0.742, and 0.754.ConclusionsThe Morse Fall Scale demonstrates good predictive performance for assessing fall risk in gynecology and obstetrics wards. The optimal cut-off score is 40.

A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) -LC-MS/MS method was developed for the determination of hexachlorophene in fruits and vegetables. Samples were extracted by acetonitrile and then salted with an acetate buffer system. Extractants neutral alumina (Al-N), strong cation exchange silica gel bonded adsorbent (SCX) and graphitized carbon black (GCB) were used for sample purification. The method demonstrates excellent accuracy and reproducibility. Under optimized conditions, the correlation coefficients of hexachlorophene were higher than 0.995 in the range of 0.5-20 ng/mL. The limit of quantification (LOQ) was 2.0 μg/kg. The average recoveries, assessed at three spiked levels (2.0, 4.0, and 20.0μg/kg) across various matrices including cabbage, celery, tomato, eggplant, potato, radish, cowpea, chives, apple, peach, grape, citrus, bitter melon, banana and hami melon ranged from 72.0 to 100.5% with relative standard deviations from 3.2 to 9.8% (n = 6).

The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS.

BackgroundSevere acute lung failure (ALF) often necessitates veno-venous extracorporeal membrane oxygenation (VV-ECMO), where identifying predictors of weaning success and mortality remains crucial yet challenging. The study aims to identify predictors of weaning success and mortality in adults undergoing VV-ECMO for severe ALF, a gap in current clinical knowledge.Methods and analysisPubMed, EMBASE, and the Cochrane Central Register of Controlled Trials will be searched for cohort studies examining the predictive factors of successful weaning and mortality in adult patients on VV-ECMO due to severe ALF. Risk of bias assessment will be conducted using the Newcastle-Ottawa scale for each included study. The primary outcomes will be successful weaning from VV-ECMO and all-cause mortality. Between-study heterogeneity will be evaluated using the I2 statistic. Sensitivity, subgroup, and meta-regression analyses will be performed to ascertain potential sources of heterogeneity and assess the robustness of our results. We will use the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool to recommend the level of evidence.DiscussionThis study seeks to provide clinically significant insights into predictors for weaning and mortality during VV-ECMO treatment for ALF, aiming to support clinical decisions and potentially influence health policy, thereby improving patient outcomes.Ethics and disseminationGiven the absence of direct engagement with human subjects or access to personal medical records, ethical approval for this study is deemed unnecessary. The study findings will be shared at a scientific conference either at the global or national level. Alternatively, the results will be presented for publication in a rigorously peer-reviewed journal regarding critical care medicine.

AbstractBackground Cough is a common symptom in patients with chronic obstructive pulmonary disease (COPD). Patients with cough may exhibit various clinical characteristics and experience varying outcomes based on inhaled therapies they receive.Objectives This study aimed to explore the clinical characteristics and outcomes of various inhaled therapies in COPD patients with frequent cough.Methods This was a multicenter, prospective cohort study. Of these patients, the median cough score in COPD assessment test (CAT) was two. Patients were classified into frequent cough group if they scored two or over in the first item of CAT and infrequent cough group otherwise. Patients with frequent cough were then divided into long-acting antimuscarinic (LAMA), long-acting beta2-agonist (LABA)/LAMA, inhaled corticosteroids (ICS)/LABA and ICS/LABA/LAMA groups. Minimum clinically important difference (MCID) (CAT scores decreased ≥2 from baseline) and the improvement of cough (cough score decreased ≥1 from baseline) were collected in the six-month follow-up. Frequent exacerbations (experiencing at least two exacerbations) were collected in the one-year follow-up.Results Of 906 patients, 581 (64.1%) patients reported frequent cough at the initial visit. Frequent cough was associated with the current smokers and CAT scores (p

Key Clinical Message Parathyroid lipoadenoma is a rare type of parathyroid adenoma, described as a single parathyroid adenoma with more than 50% fat on histologic examination and an unknown etiology, which is one of the rare causes of primary hyperparathyroidism. The difficulty of parathyroid lipoadenoma is mainly diagnosed by preoperative imaging localization. We hope to arouse attention to the parathyroid adenoma which is difficult to locate through our case report. The patient was a middle‐aged male with a body mass index of 38.4 kg/m2 who admitted to our hospital with a 40‐day history of an untreated thyroid nodule. We incidentally discovered parathyroid lipoadenoma in his thyroid surgery. His prognosis was good, and there were no signs of recurrence at his 12‐month follow‐up appointment. We believe that parathyroid lipoadenoma needs to rely on paraffin pathology to make a final diagnosis. This case report serves as a reminder that parathyroid lipoadenomas are also possible in patients who do not have primary hyperparathyroidism preoperatively and who have negative imaging. Clinicians must carefully examine the adipose tissue for the presence of parathyroid lipoadenomas during thyroid surgery to avoid postoperative hypoparathyroidism and persistent hypocalcaemia.

AbstractBackground Although there is an assertion that weather conditions affect osteoarthritis (OA) pain, the results from clinical studies remain inconsistent. This meta-analysis was performed to evaluate the association between weather conditions and OA pain.Methods Cochrane Library, Embase, PubMed, and Web of Science were searched from inception to September 30, 2022. Observational studies that explored all weather conditions associated with pain intensity were included. In the systematic review, the methodological quality of the selected studies was assessed and a best-evidence synthesis was used to make qualitative conclusions. Based on homogeneous results, Fisher’s Z scores derived from the effect size of temperature (T), barometric pressure (BP) or relative humidity (RH) related to OA pain were synthesized and further transformed to the correlation coefficients (summary r) in meta-analysis.Results A total of 14 studies were included in the best-evidence synthesis of a qualitative systematic review. There was strong evidence with 13 of 14 studies reporting consistent findings that weather factors in general, including any kind of meteorological condition, were associated with OA pain. Subsequently, 3 studies regarding BP or T, and 5 studies regarding RH with the pain of OA were included in quantitative meta-analyses. Both BP (pooled Fisher’s Z = 0.37, 95% CI 0.15 to 0.59; summary r = 0.35, 95% CI 0.15 to 0.53) and RH (pooled Fisher’s Z = 0.10, 95% CI 0.01 to 0.18; summary r = 0.086, 95% CI −0.05 to 0.22) were positively related to OA pain, while T was negatively related to OA pain (pooled Fisher’s Z = −0.38, 95% CI −0.60 to −0.16; summary r = −0.36, 95% CI −0.54 to −0.16).Conclusions In this study, weather factors in general were significantly associated with OA pain. It may provide useful references for the daily health management of OA. More studies designed with the consistent meteorological condition are warranted to validate the findings.KEY MESSAGEMany people with osteoarthritis think their joint pain is affected by the weather, while the association between OA pain and weather conditions is still unclear.This is a systematic review and meta-analysis of 14 observational studies for the association between weather conditions and OA pain.Weather conditions appear to be associated with OA pain. Barometric pressure and relative humidity were positively correlated to OA pain intensity, while temperature was negatively correlated to OA pain.

Abstract Freshwater pollution and shortage have become an imminent problem. Therefore, it is necessary to develop a multi-functional membrane for the production of fresh water. In this work, the regenerated lignocellulose modified cotton fabric was developed as a novel, multi-functional and degradable membrane (LCPT@CF) for efficient oil–water separation and solar steam generation for the first time. The fabrication method has the merits of simple, environmentally friendly and cost effective. The regenerated lignocellulose was adhered on the surface of cotton fabric by tannic acid and polyvinyl alcohol complexes tightly, and the multilayered structures of the LCPT@CF can be formed, which endowed the membranes with underwater superoleophobic property and durability. The underwater superoleophobic property enabled LCPT@CF to purify various kinds of oil-in-water emulsions with a separation efficiency of more than 99.90%. Moreover, benefiting from the excellent photothermal conversion capacity of regenerated lignocellulose, the LCPT@CF achieved high evaporation rate of 1.39 kg m−2 h−1 and favorable evaporation efficiency of 84% under 1 sun illumination, and the LCPT@CF also presented excellent salt-resistance for evaporating seawater for 20 cycles, without salt accumulation. More importantly, the LCPT@CF could be naturally degradable by microorganisms in the natural condition within 3 months, which had outstanding environmental friendliness. These above results demonstrated that the green and efficient LCPT@CF could play great potential in oil–water separation and sewage purification.

Abstract Background Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance, with the underlying mechanisms remaining to be explored. Methods We characterized the transcriptomes of ~92,000 single cells from 3 pre-treatment and 12 post-treatment patients with non-small cell lung cancer (NSCLC) who received neoadjuvant PD-1 blockade combined with chemotherapy. The 12 post-treatment samples were categorized into two groups based on pathologic response: major pathologic response (MPR; n = 4) and non-MPR (NMPR; n = 8). Results Distinct therapy-induced cancer cell transcriptomes were associated with clinical response. Cancer cells from MPR patients exhibited a signature of activated antigen presentation via major histocompatibility complex class II (MHC-II). Further, the transcriptional signatures of FCRL4+FCRL5+ memory B cells and CD16+CX3CR1+ monocytes were enriched in MPR patients and are predictors of immunotherapy response. Cancer cells from NMPR patients exhibited overexpression of estrogen metabolism enzymes and elevated serum estradiol. In all patients, therapy promoted expansion and activation of cytotoxic T cells and CD16+ NK cells, reduction of immunosuppressive Tregs, and activation of memory CD8+T cells into an effector phenotype. Tissue-resident macrophages were expanded after therapy, and tumor-associated macrophages (TAMs) were remodeled into a neutral instead of an anti-tumor phenotype. We revealed the heterogeneity of neutrophils during immunotherapy and identified an aged CCL3+ neutrophil subset was decreased in MPR patients. The aged CCL3+ neutrophils were predicted to interact with SPP1+ TAMs through a positive feedback loop to contribute to a poor therapy response. Conclusions Neoadjuvant PD-1 blockade combined with chemotherapy led to distinct NSCLC tumor microenvironment transcriptomes that correlated with therapy response. Although limited by a small patient sample size subjected to combination therapy, this study provides novel biomarkers to predict therapy response and suggests potential strategies to overcome immunotherapy resistance.

Background and aim: The present study was conducted to evaluate the diagnostic accuracy of Superparamagnetic iron oxide nanoparticles in breast cancer.Material and methods: We examined all international databases, including PubMed, Scopus, Science Direct, ISI, Web of Knowledge, and Embase, searching until January 2023 based on keywords related to the objectives of the study. Based on the PRISMA 2020 checklist, the current study was conducted, and the Google Scholar search engine was also used to find related articles. A fixed-effect model and inverse-variance method were used to calculate the 95% confidence interval risk ratio. The meta-analysis was conducted using Stata/MP v. 17 software.Results: The abstracts of 477 articles were reviewed, and 51 articles were selected for full-text review, of which 15 articles were included in the meta-analysis. The risk ratio of patient detection rate between superparamagnetic iron oxide nanoparticles and the standard method was 1.02 (RR, 1.02 95% CI 0.52, 1.53; p>0.05). Compared to the control group, the superparamagnetic iron oxide nanoparticles group showed a higher superiority in extracting more SLN (RR, 1.07 95% CI 0.52, 1.61; p

Objective The dysregulation of the human high-temperature requirement A (HtrA) family of serine proteases is associated with many malignancies. However, there are few reports on HtrAs in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the expression, prognostic value, and biological functions of HtrAs in HNSCC. Methods The RNA-sequencing data and clinical data of HNSCC were downloaded from The Cancer Genome Atlas (TCGA) database. The GSE30784 and GSE31056 datasets from the Gene Expression Omnibus (GEO) database were used for further verification. This study explored the differential expression of HtrAs and assessed their potential impact on the prognosis of HNSCC patients using a survival module. Correlations between clinical characteristics and HtrA expression levels were then explored using a Wilcoxon rank sum test. A Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed using “clusterProfile” in the R software. A Pearson/Spearman correlation test was applied to analyze the relationship between HtrAs and immune infiltration level/checkpoint genes. Validation of HtrA expression levels were carried out by RT-PCR and western blot in human squamous carcinoma cell lines (Fadu and Cal-27) and human non-tumorigenic bronchial epithelium cells (BEAS-2B). Finally, through cell transfection, CCK-8, Ki-67 immunofluorescence, and flow cytometry assays, the effect of HtrA3 knockdown on the malignant biological behavior of HNSCC cells was explored. Results The gene expression levels of HtrAs were significantly upregulated and associated with patient age, TNM stage, clinical stage, and TP53 mutation status in the TCGA-HNSCC cohort. High expressions of HtrA1/3 were associated with shorter overall survival, shorter progress-free interval, and lower disease-specific survival in HNSCC. A nomogram for HtrAs was constructed and validated. HtrA-related genes were significantly enriched in the immune response and cell apoptosis pathway. In addition, the expression of HtrAs showed significant correlations with B cells, M cells, DC cell infiltration, and immune infiltration checkpoint (CD276, TNFRSF14). Validation of HtrA expression was carried out by RT-PCR and western blot. Results of in vitro experiments indicated that HtrA3 gene knockdown inhibits the proliferation of FaDu and Cal-27 cells while concurrently promoting apoptosis. Conclusions HtrA3 shows significant potential as both a prognostic marker and a promising therapeutic target for HNSCC, highlighting its relevance and importance in future research and potential clinical applications.

Abstract This study aimed to investigate the therapeutic efficacy of programmed spatial anatomy of myopectineal orifice technique in laparoscopic total extraperitoneal hernioplasty (TEP) surgery. A total of 121 adult male patients with unilateral inguinal hernias who underwent TEP in the Department of General Surgery, Wujin Hospital, affiliated with Jiangsu University, from January 2019 to December 2020 were selected. Patients were divided into the procedural (63 cases) and traditional groups (58 cases) according to the surgical methods adopted. The procedural group underwent programmed spatial anatomy of the myopectineal orifice combined with TEP, and the traditional group underwent traditional TEP. The perioperative evaluation indicators and postoperative complications were observed and compared between the two groups. Compared with the traditional group, the time of handling hernia, the intraoperative operation time, intraoperative blood loss, postoperative ambulation time, and postoperative hospital stay in the procedural group were significantly reduced (P 0.05). The programmed spatial anatomy of the myopectineal orifice can significantly improve the treatment outcome of TEP, significantly improve the patients' intraoperative and postoperative indicators, and reduce the incidence of postoperative complications. It is worthy of being promoted among young physicians and basic hospitals.

Objective To study the protective effect of dexmedetomidine (DEX) on human neuroblastoma cell line SH-SY5Y under anoxia condition and its specific mechanism. Methods SH-SY5Y cells were divided into control group, anoxia group (treated with final concentration of 1.2 mmol/L CoCl2 for 24 h) and DEX intervention group (treated with final concentration of 1.2 mmol/L CoCl2 and 10 μmol/L DEX for 24 h). Cell morphology was observed by microscope; Cell viability and apoptosis were detected by MTT assay, TUNEL staining and annexin V-FITC/PI staining; The expression levels of cleaved caspase-9, cleaved caspase-3, p75NTR and p-NF-κB proteins were detected by Western blot. Results Compared with control group, the cell size in anoxia group was shrinked(PPPNTR and p-NF-κB proteins was all significantly increased (PPConclusions Alleviation of anoxia-induced SH-SY5Y cell injury is potentially mediatd by inhibiting p75NTR expression and NF-κB activity.