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Abstract Purpose To develop MRI-based deep learning (DL) models for distinguishing sinonasal squamous cell carcinoma (SCC), adenoid cystic carcinoma (ACC) and olfactory neuroblastoma (ONB) and to evaluate whether the DL models could improve the diagnostic performance of Senior radiologist (SR) and Junior radiologist (JR). Methods This retrospective analysis consisted of 465 patients (229 sinonasal SCCs, 128 ACCs and 108 ONBs). The training and validation cohorts included 325 and 47 patients and the independent external testing cohort consisted of 93 patients. MRI images included T2-weighted image (T2WI), contrast-enhanced T1-weighted image (CE-T1WI) and apparent diffusion coefficient (ADC). We analyzed the conventional MRI features to choose the independent predictors and built the conventional MRI model. Then we compared the macro- and micro- area under the curves (AUCs) of different sequences and different DL networks to formulate the best DL model [artificial intelligence (AI) model scheme]. With AI assistance, we observed the diagnostic performances between SR and JR. The diagnostic efficacies of SR and JR were assessed by accuracy, Recall, precision, F1-Score and confusion matrices. Results The independent predictors of conventional MRI included intensity on T2WI and intracranial invasion of sinonasal malignancies. With ExtraTrees (ET) classier, the conventional MRI model owned AUC of 78.8%. For DL models, ResNet101 network showed better performance than ResNet50 and DensNet121, especially for the mean fusion sequence (macro-AUC = 0.892, micro-AUC = 0.875, Accuracy = 0.810), and also good for the ADC sequence (macro-AUC = 0.872, micro-AUC = 0.874, Accuracy = 0.814). Grad-CAM showed that DL models focused on solid component of lesions. With the best AI scheme (ResNet101-mean sequence-based DL model) assistance, the diagnosis performances of SR (accuracy = 0.957, average Recall = 0.962, precision = 0.955, F1-Score = 0.957) and JR (accuracy = 0.925, average Recall = 0.917, precision = 0.931, F1-Score = 0.923) were significantly improved. Conclusion The ResNet101 network with mean sequence based DL model could effectively differential between sinonasal SCC, ACC and ONB and improved the diagnostic performances of both senior and junior radiologists.

Abstract Background Asthma is a significant public health issue that cannot be ignored in China and around the world, bringing a huge social burden. Objectives To evaluate the disease burden of asthma in China, including health loss and cost of illness, and identify its influencing factors. Methods A systematic literature review and qualitative descriptive analysis were conducted, Literature was accessed through PubMed, EMBASE, Web of Science, CNKI, Wangfang Data, and VIP databases, with a cutoff date of April 3, 2024. The analysis focused on two main aspects: health loss burden, measured by disability-adjusted life years (DALYs), including years of life lost (YLLs) and years lived with disability (YLDs); and economic burden, assessed through direct and indirect costs. The risk of bias in economic studies was assessed using an 11-item methodological checklist for cost of illness, while cross-sectional studies were evaluated using the Agency for Healthcare Research and Quality’s recommendation rating tool. Results The analysis included 50 studies, with eight focused on health loss and 42 on economic burden. The health loss studies showed a 51% decrease in asthma's age-standardized DALYs rate over 30 years, from 209.24 to 102.81 per 100,000 person-years. The health loss burden is influenced by factors such as high BMI, smoking, and occupational exposure. Economic burden studies reported annual direct costs from $348 to $1187 per capita, indirect costs from $7 to $1195, and hospitalization costs from $177 to $1547, influenced by frequency and severity of acute exacerbation, comorbidities, and treatment adherence. Quality assessment revealed moderate overall quality, with gaps in sensitivity analyses and cost data transparency. Conclusion The health loss burden of asthma in China has significantly decreased from 1990 to 2019, with males experiencing a higher burden. However, regional disparities in the economic burden persist, highlighting the need for improved management and adherence to standardized treatment protocols to address these disparities.

Abstract Background Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a rare hereditary disorder caused by variants in PKHD1. Currently, aberrant splicing has been reported to play important roles in genetic disease. Our goal is to analyze intronic variants in PKHD1 at the mRNA level. Results The 12 candidate variants were introduced into the corresponding minigene and functionally assayed in HEK 293T and Hela cells. We identified 11 variants that induce splicing alterations, resulting in various consequences such as skipping of exons, intron retention and protein truncation. Conclusions This underlined the importance of mRNA-level assessment for genetic diagnostics in related genetic disorders.

Precipitation (P) is the sole water source supporting plant growth in the desert steppe, governing the structure and function of plant communities. Nevertheless, how changes in precipitation alter species composition and affect interspecific relationships within plant communities remains unclear. To address this, we simulated five precipitation gradients, ranging from 50 % (P−50 %), 70 % (P−30 %), 100 % (PCK), 130 % (P+30 %), to 150 % (P+50 %) relative to ambient precipitation. We assessed the effects of precipitation treatments and seasonality on plant community structure and species composition in late spring, mid-summer, and late summer. Results showed that (1) The desert grassland plant community exhibited an asymmetric response to precipitation amount and seasonal variatt steppe ecosystems, interspecific connectivity reflecion, where the impact of late-spring precipitation on the quantitative traits, importance values (IV), and mean niche overlap of communities was greater than that of mid-summer and late-summer precipitation, and the effects of decreased precipitation were more significant than those of increased precipitation. (2) The niche of perennial plants did not change with the season, while the IV and ecological niche width (B) of annual plants increased as the seasons passed. (3) Decreased precipitation reduced the mean niche overlap of all species, the B of Leguminosae plants, and the IV of all species except for Stipa breviflora and Convolvulus ammannii. (4) The overall association index indicated a positive correlation among communities, showing significant correlations in P+50 %, P−30 %, and P−50 %. The association index between populations gradually shifted from negative to positive with decreasing precipitation. Therefore, we suggest that both drought and wetness tend to intensify interspecific interactions within the community. More importantly, drought transformed the population relationships from competition to mutualistic symbiosis.

ABSTRACTDiet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.

Optimizing the nitrogen (N) fertilization level and cropping system is critically important for achieving good production performance with low environmental pollution. However, there is a knowledge gap on the relationship between crop production sustainability, water and nitrogen consumption, greenhouse gas (GHG) emission under the change in N application rate under cereal and legume mixed systems. A 3-year field experiment with two cropping systems [sole forage sorghum (SS) and forage sorghum/lablab mixed cropping (SL) with four N fertilizer application rates (N0, 0 kg N ha−1; N90, 90 kg N ha−1; N180, 180 kg N ha−1; and N270, 270 kg N ha−1)] was conducted. Results obtained showed that mixed cropping combined with N fertilization enhanced forage biomass and crude protein yield by 34.0 % and 51.1 %, respectively, particularly in mixed cropping combined with the N180 treatment compared with the N0 level in the sole cropping system. Similar improvements were observed for yield stability and sustainability (2.97 % and 0.95, respectively), which reached maximum values at N180 in the mixed cropping system. In addition, mixed cropping increased the water productivity of dry matter yield (WPDM) and water productivity of crude protein yield (WPCPY) by 17.2 % and 27.6 %, respectively, at 180 kg N ha−1 compared with the corresponding treatments of the sole planting system. Furthermore, mixed cropping combined with appropriate N application significantly improved N physiological efficiency (PEN) and reduced GHG intensity (GHGI), where N application of 180 kg ha−1 N increased PEN by 21.3 % and reduced GHGI by 17.6 % compared with the corresponding monoculture in the mixed cropping system. This study demonstrated that reducing N fertilization in cereal–legume cropping systems can promote forage productivity by optimizing water and N management while decreasing environmental pollution. Therefore, forage sorghum mixed with lablab and fertilization at 180 kg N ha–1 is a preferable approach for sustainable agricultural production in the Northwest arid region of China.

Abstract Background Patient-centered health care for patients with pulmonary hypertension (PH) is important and requires an understanding of patient experiences. However, there is a lack of approaches to examine what's the effects and how the disease impact patients’ psychological well-beings. Methods We conducted qualitative interviews with PH patient representatives to understand patient psychological experiences and inform patient-centered research and care. Participants were chosen from a tertiary hospital located in northwest China. 20 patients with PH who be treated at the hospital (13 participants were women, aged 18-74 years) were strategically selected and individually interviewed. We used qualitative analysis to identify themes relating to existential psychological distress that would clarify the nature of such concerns. Results We found that patients experience tremendous psychological distress throughout the treatment process. Four categories that describe patients' psychological experiences emerged: burden of PH treatment, fear and uncertainty about the disease, frustration in social and family role, and lack of recognition of the condition. Conclusions Existential concerns are salient in PH and involve the experience of loss and disruptions to the sense of self and relationships. Healthcare practitioners must work more in collaboration to detect patients' need for support and to develop the patient's own skills to manage daily life. The PH teams should tailor interventions to provide emotional, informational and instrumental support and guidance to patients.

Obesity is a complex, multifactorial condition involving excessive fat accumulation due to an imbalance between energy intake and expenditure, with its global prevalence steadily rising. This condition significantly increases the risk of chronic diseases, including sarcopenia, type 2 diabetes, and cardiovascular diseases, highlighting the need for effective interventions. Exercise has emerged as a potent non-pharmacological approach to combat obesity, targeting both central and peripheral mechanisms that regulate metabolism, energy expenditure, and neurological functions. In the central nervous system, exercise influences appetite, mood, and cognitive functions by modulating the reward system and regulating appetite-controlling hormones to manage energy intake. Concurrently, exercise promotes thermogenesis in adipose tissue and regulates endocrine path-ways and key metabolic organs, such as skeletal muscle and the liver, to enhance fat oxidation and support energy balance. Despite advances in understanding exercise’s role in obesity, the precise interaction between the neurobiological and peripheral metabolic pathways remains underexplored, particularly in public health strategies. A better understanding of these interactions could inform more comprehensive obesity management approaches by addressing both central nervous system influences on behavior and peripheral metabolic regulation. This review synthesizes recent insights into these roles, highlighting potential therapeutic strategies targeting both systems for more effective obesity interventions.

Background: The adverse effects of pulmonary arterial hypertension (PAH) on physical, emotional, and health-related quality of life (HRQoL) remain primarily unrecognized, especially in resource-limited settings. Objectives: This study aims to characterize the HRQoL of patients with PAH in this area and also identify the potential role of clinically relevant characteristics, including the 6-min walk distance test (6MWD), WHO-Functional Classification (WHO-FC), and mental health in the occurrence of lowering quality of life. Design: This was a cross-sectional observational study. Methods: Inpatients with PAH were chosen from a tertiary hospital located in Gansu province, China. All participants were interviewed face-by-face by using questionnaires, including items from the 36-Item Short Form Health Survey (SF-36), the self-rating anxiety scale, and the self-rating depression scale. Data on demographic and clinically relevant characteristics, including WHO-FC and 6MWD, were also collected by tracing medical recorders. Multiple linear regression analysis was used to determine the association between demographic, clinically relevant characteristics data, and physical component summary (PCS) or mental component summary (MCS) in SF-36. Results: Of the 152 participants, SF-36 differed significantly from Chinese norms in all eight domains, with role-physical (21.55 ± 9.87) less than one-third of the norm (88.79 ± 28.49). Multiple linear regression results showed that the factors with the greatest impact on PCS were anxiety scores (β = −0.22, p = 0.001), followed by WHO-FC (β = −0.16, p = 0.014) and 6MWD (β = 0.15, p = 0.036). The factors with the greatest impact on MCS were WHO-FC (β = −0.30, p

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic multisystem disease caused primarily by mutations in the PKD1 gene or PKD2 gene. There is increasing evidence that some of these variants, which are described as missense, synonymous or nonsense mutations in the literature or databases, may be deleterious by affecting the pre-mRNA splicing process. Results This study aimed to determine the effect of these PKD1 and PKD2 variants on exon splicing combined with predictive bioinformatics tools and minigene assay. As a result, among the 19 candidate single nucleotide alterations, 11 variants distributed in PKD1 (c.7866C > A, c.7960A > G, c.7979A > T, c.7987C > T, c.11248C > G, c.11251C > T, c.11257C > G, c.11257C > T, c.11346C > T, and c.11393C > G) and PKD2 (c.1480G > T) were identified to result in exon skipping. Conclusions We confirmed that 11 variants in the gene of PKD1 and PKD2 affect normal splicing by interfering the recognition of classical splicing sites or by disrupting exon splicing enhancers and generating exon splicing silencers. This is the most comprehensive study to date on pre-mRNA splicing of exonic variants in ADPKD-associated disease-causing genes in consideration of the increasing number of identified variants in PKD1 and PKD2 gene in recent years. These results emphasize the significance of assessing the effect of exon single nucleotide variants in ADPKD at the mRNA level.

Abstract Background X‐linked Alport syndrome (XLAS) is an inherited renal disease caused by rare variants of COL4A5 on chromosome Xq22. Many studies have indicated that single nucleotide variants (SNVs) in exons can disrupt normal splicing process of the pre‐mRNA by altering various splicing regulatory signals. The male patients with XLAS have a strong genotype–phenotype correlation. Confirming the effect of variants on splicing can help to predict kidney prognosis. This study aimed to investigate whether single nucleotide substitutions, located within three bases at the 5′ end of the exons or internal position of the exons in COL4A5 gene, cause aberrant splicing process. Methods We analyzed 401 SNVs previously presumed missense and nonsense variants in COL4A5 gene by bioinformatics programs and identified candidate variants that may affect the splicing of pre‐mRNA via minigene assays. Results Our study indicated three of eight candidate variants induced complete or partial exon skipping. Variants c.2678G>C and c.2918G>A probably disturb classic splice sites leading to corresponding exon skipping. Variant c.3700C>T may disrupt splicing enhancer motifs accompanying with generation of splicing silencer sequences resulting in the skipping of exon 41. Conclusion Our study revealed that two missense variants positioned the first nucleotides of the 5′ end of COL4A5 exons and one internal exonic nonsense variant caused aberrant splicing. Importantly, this study emphasized the necessity of assessing the effects of SNVs at the mRNA level.

Abstract Background As a practice-oriented discipline, strict adherence to reporting guidelines is particularly important in randomized controlled trial (RCT) abstracts of the nursing area. However, whether abstract reports after 2010 have complied with the Consolidated Standards of Reporting Trials for Abstracts (CONSORT-A) guideline is unclear. This study aimed to evaluate whether the publication of CONSORT-A has improved abstract reporting in nursing and explores the factors associated with better adherence to the guidelines. Methods We searched the Web of Science for 200 RCTs randomly selected from ten nursing journals. We used a data extraction form based on CONSORT-A, including 16 items, to analyze the reporting adherence to the guidelines, and the reporting rate of each item and the total score for each abstract were used to indicate adherence and overall quality score (OQS, range 0–16). A comparison of the total mean score between the two periods was made, and affecting factors were analyzed. Results In the studies we included, 48 abstracts were published pre-CONSORT-A whereas 152 post-CONSORT-A. The overall mean score for reporting adherence to 16 items was 7.41 ± 2.78 and 9.16 ± 2.76 for pre- and post-CONSORT-A, respectively (total score: 16). The most poorly reported items are “harms (0%),” “outcomes in method (8.5%),” “randomization (25%),” and “blinding (6.5%).” Items including the year of publication, impact factor, multiple center trial, word count, and structured abstract are significantly associated with higher adherence. Conclusions The adherence to abstract reporting in nursing literature has improved since the CONSORT-A era, but the overall completeness of RCT abstracts remained low. A joint effort by authors, editors, and journals is necessary to improve reporting quality of RCT abstracts.

Abstract Aim The aim of this study is to describe critical thinking dispositions among newly graduated nurses with different educational background in China and to explore related factors. Design A cross‐sectional questionnaire survey. Methods The data were collected using the Chinese Version of Critical Thinking Dispositions Inventory (CTDI‐CV). Overall, 588 newly graduated nurses finally completed the survey. Spearman and Pearson's correlation coefficients were used to examine the correlation between the CDTI‐CV and nurses' general characteristics. Results In terms of open‐mindedness, analysis and inquisitiveness subscales, significant differences were found among nurses based on three educational level. When dichotomizing total CTDI scores into high and low, nearly 80% of the respondents fell into low score group. Pressure from workplace was high for 68.4% of them. Significant correlation was found among the new graduated nurses' critical thinking ability and their age, education level, reading habit and attitude towards nursing profession.

Inflammatory bowel disease (IBD) is a chronic, immune-mediated inflammatory disease characterized by the destruction of the structure and function of the intestinal epithelial barrier. Due to the poor remission effect and severe adverse events associated with current clinical medications, IBD remains an incurable disease. Here, we demonstrated a novel treatment strategy with high safety and effective inflammation remission via tissue-adhesive molecular coating. The molecular coating is composed of o-nitrobenzaldehyde (NB)-modified Gelatin (GelNB), which can strongly bond with –NH2 on the intestinal surface of tissue to form a thin biophysical barrier. We found that this molecular coating was able to stay on the surface of the intestine for long periods of time, effectively protecting the damaged intestinal epithelium from irritations of external intestinal metabolites and harmful flora. In addition, our results showed that this coating not only provided a beneficial environment for cell migration and proliferation to promote intestinal repair and regeneration, but also achieved a better outcome of IBD by reducing intestinal inflammation. Moreover, the in vivo experiments showed that the GelNB was better than the classic clinical medication—mesalazine. Therefore, our molecular coating showed potential as a promising strategy for the prevention and treatment of IBD.

The microRNAs (miRNAs) are potent regulators of tumorigenesis in various cancers, especially pancreatic cancer. The abnormal expression of miRNAs can be observed in tumor cells. Noteworthy, miRNAs could be transferred by exosomes as small extracellular vesicles in regulation of carcinogenesis. This research focused on exploring the roles and mechanisms of exosomal miR-484, derived from human bone marrow mesenchymal stem cells (hBMSCs), in the context of molecular interactions and regulation of mitochondrial metabolism. Exosomes were isolated for the examination of miR-484 expression. The impacts of hBMSCs-derived exosomal miR-484 on pancreatic cancer cells were studied using various assays. Evaluation of mitochondrial function and metabolism was performed. Wnt/MAPK pathway-related protein expression was assessed, and an in vivo tumor xenograft model was utilized to examine the functions. Our findings demonstrated a decreased miR-484 expression in pancreatic cancer cells. However, hBMSCs-derived exosomal miR-484 inhibited the proliferation and migration of these cells, while inducing apoptosis. Moreover, miR-484 led to an upsurge in reactive oxygen species production, a decrease in ATP levels, and a disruption in mitochondrial metabolism. In vivo analyses showed that hBMSCs-derived exosomal miR-484 lessened tumor size and weight, while also suppressing the expression of mitochondrial biomarkers. Further, there was a decline in β-catenin and p-p38 protein levels both in vitro and in vivo. The addition of LiCl restored the disrupted mitochondrial metabolism. Conclusively, our results suggest that hBMSCs-derived exosomal miR-484 mitigates the malignant transformation and mitochondrial metabolism of pancreatic cancer by deactivating the Wnt/MAPK pathway.

Apples are usually bagged during the growing process, which can effectively improve the quality. Establishing an in situ nondestructive testing model for in-tree apples is very important for fruit companies in selecting raw apple materials for valuation. Low-maturity apples and high-maturity apples were acquired separately by a handheld tester for the internal quality assessment of apples developed by our group, and the effects of the two maturity levels on the soluble solids content (SSC) detection of apples were compared. Four feature selection algorithms, like ant colony optimization (ACO), were used to reduce the spectral complexity and improve the apple SSC detection accuracy. The comparison showed that the diffuse reflectance spectra of high-maturity apples better reflected the internal SSC information of the apples. The diffuse reflectance spectra of the high-maturity apples combined with the ACO algorithm achieved the best results for SSC prediction, with a prediction correlation coefficient (Rp) of 0.88, a root mean square error of prediction (RMSEP) of 0.5678 °Brix, and a residual prediction deviation (RPD) value of 2.466. Additionally, the fruit maturity was predicted using PLS-LDA based on color data, achieveing accuracies of 99.03% and 99.35% for low- and high-maturity fruits, respectively. These results suggest that in-tree apple in situ detection has great potential to enable improved robustness and accuracy in modeling apple quality.

Abstract Precision medicine is the ultimate goal for current disease therapies, including tumor and infection. The lack of specific targeted drugs for liver cancer and the lack of specific anti-infective drugs in the treatment of diabetic foot ulcer with infection (DFI) are the representative obstacles in those 2 major diseases currently plaguing human beings. Inventing natural biocompatible polymers derived from natural materials is one of the main development directions of current bio-medical materials. Though previous studies have demonstrated the potential application values of human black hair-derived nanoparticles (HNP) in cancer, methicillin-resistant Staphylococcus aureus (MRSA) infection, and thrombosis scenarios treatments, it still has not solved the problem of low local therapeutic concentration and general targeting ability. Here, we firstly modified the HNP with membrane encapsulations, which endowed these dual-pure natural bio-fabricated materials with better targeting ability at the disease sites with no reduction in photothermal therapy (PTT) effect. HNP coated by red blood cell membrane loaded with DSPE-PEG-cRGD peptide for the therapeutic application of liver cancer greatly prolonged in vivo circulation time and enhanced local targeting efficacy as well as low toxicity; HNP coated by the murine macrophage cell membrane (RAWM) for the DFIs treatment greatly promoted the adhesive ability of HNP on the bacteria and thereby improved the killing effect. Briefly, the appropriate cell membranes camouflaged HNP nanomedicine has the characteristics of excellent photothermal effect, an all-natural source with excellent biocompatibility and easy access, which is expected to have huge potential in both benign and malignant diseases.

BackgroundThis study aimed to understand the hospital-acquired COVID-19 infection rate and infection prevention and control status of emergency support frontline healthcare workers (ESFHCWs) under closed-loop management, and to explore the related factors affecting hospital-acquired COVID-19 prevention and control status.MethodsThe study site was a provincial-level tertiary hospital in the Xinjiang Uygur Autonomous Region specializing in treating COVID-19 patients. ESFHCWs were assigned from different hospitals in Zhejiang Province to provide emergency medical support in this specialized hospital. All ESFHCWs were managed using a closed loop. A self-designed questionnaire was used to estimate basic information, work experience, and the status of infection prevention and control (SIPC). A total of 269 ESFHCWs responded to the questionnaire. A generalized linear regression model was used to estimate the factors influencing SIPC.ResultsThere were six hospital-acquired COVID-19 cases, with an infection rate of 2.23%. The independent risk factors influencing COVID-19 prevention and control status were work seniority, anxiety disorder, and consumption of gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs. Compared with ESFHCWs with more than 10 years of work seniority, ESFHCWs with less than 5 years of work seniority and 5–10 years of work seniority had lower COVID-19 SIPC scores. Among ESFHCWs with anxiety disorder, the SIPC score was significantly lower than that of ESFHCWs without anxiety disorder. The SIPC scores of ESFHCWs taking other medications (gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs) were lower than those of ESFHCWs who did not.ConclusionThe closed-loop management method may be effective in reducing the infection rate of hospital-acquired COVID-19 among ESFHCWs. HCWs with less than 10 years of work seniority, anxiety disorder, and other medications (gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs) were probably not suitable for participating in emergency assistant actions because of their poor SIPC scores. Further studies are needed to develop the selection criteria for ESFHCWs.

Abstract Cell membrane encapsulation is a growing concept in nanomedicine, for it achieves the purpose of camouflage nanoparticles, realizing the convenience for drug delivery, bio‐imaging, and detoxification. Cell membranes are constructed by bilayer lipid phospholipid layers, which have unique properties in cellular uptake mechanism, targeting ability, immunomodulation, and regeneration. Current medical applications of cell membranes include cancers, inflammations, regenerations, and so on. In this article, a general bibliometric overview is conducted of cell membrane‐coated nanoparticles covering 11 years of evolution in order to provide researchers in the field with a comprehensive view of the relevant achievements and trends. The authors analyze the data from Web of Science Core Collection database, and extract the annual publications and citations, most productive countries/regions, most influential scholars, the collaborations of journals and institutions. The authors also divided cell membranes into several subgroups to further understand the application of different cell membranes in medical scenarios. This study summarizes the current research overview in cell membrane‐coated nanoparticles and intuitively provides a direction for future research.

Objective: To evaluate the reporting quality of randomized controlled trial (RCT) abstracts regarding patients with coronavirus disease 2019 (COVID-19) and to analyze the factors influencing the quality. Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched to collect RCTs on patients with COVID-19. The retrieval time was from inception to December 1, 2020. The CONSORT statement for abstracts was used to evaluate the reporting quality of RCT abstracts. Results: A total of 53 RCT abstracts were included. The CONSORT statement for abstracts showed that the average reporting rate of all items was 50.2%. The items with a lower reporting quality were mainly the trial design and the details of randomization and blinding (

PurposeThis study aims to assess the prognostic value of inflammatory markers and clinical features in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients receiving anti-programmed death 1 (PD-1) treatment.MethodsBased on receiver operating characteristic curve (ROC) analysis, Youden’s indexes were applied to determine the cut-off values for inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocye ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Wilcoxon test was conducted to evaluate the changes in above inflammatory markers. Kaplan-Meier method was utilized to estimate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used to compare the different survival between groups. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of inflammatory markers and clinical features.Results162 advanced or metastatic ESCC patients receiving anti-PD-1 treatment were enrolled in this retrospective study. The cut-off values of NLR, dNLR, MLR, PLR, and SII were 4.748, 2.214, 0.309, 250.505, and 887.895, respectively. NLR, dNLR, PLR, and SII declined significantly among the partial response (PR) (P

Cuproptosis was characterized as a novel type of programmed cell death. Recently, however, the role of cuproptosis-related long noncoding RNAs (CRLs) in tumors has not yet been studied. Identifying a predictive CRL signature in hepatocellular carcinoma (HCC) and investigating its putative molecular function were the goals of this work. Initially, Pearson’s test was used to assess the relationship between lncRNAs and cuproptosis-associated genes obtained from HCC data of The Cancer Genome Atlas (TCGA). By implementing differential expression and univariate Cox analysis, 61 prognostic CRLs were subsequent to the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. A prognostic risk score model was then constructed to evaluate its ability to predict patients’ survival when combined with clinicopathological parameters in HCC. The five-lncRNA prognostic signature categorized the HCC patients into high- and low-risk groups. The low-risk group exhibited more sensitivity to elesclomol than the high-risk one. Surprisingly, distinct mitochondrial metabolism pathways connected to cuproptosis and pivotal immune-related pathways were observed between the two groups via gene set enrichment analysis (GSEA). Meanwhile, there were substantial differences between the high-risk group and the low-risk group in terms of tumor-infiltrating immune cells (TIICs). Furthermore, a positive relationship was shown between the risk score and the expression of immune checkpoints. Additionally, differential expression of the five lncRNAs was confirmed in our own HCC samples and cell lines via RT-qPCR. Finally, in vitro assays confirmed that WARS2-AS1 and MKLN1-AS knockdown could sensitize HCC cells to elesclomol-induced cuproptosis. Overall, our predictive signature may predict the prognosis of HCC patients in an independent manner, give a better understanding of how CRLs work in HCC, and offer therapeutic reference for patients with HCC.

Hepatic ischemia–reperfusion (IR) injury is a serious clinical problem that complicates liver resection and transplantation. Despite recent advances in understanding of the pathophysiology of hepatic IR injury, effective interventions and therapeutics are still lacking. Here, we examined the role of transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable, non-selective cation channel, in mediating hepatic IR injury. Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction, inflammation, and cell death in mice. Moreover, RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways. Consistently, as a ferroptosis inducer, (1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this. Interestingly, TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca2+-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase (ALOX12), which results in mitochondrial lipid peroxidation during hepatic IR injury. Furthermore, hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion, both in vitro and in vivo. Collectively, these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca2+-induced ALOX12 expression, indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases, such as during liver resection and transplantation.

Abstract As the predominant host defense against pathogens, neutrophil extracellular traps (NETs) have attracted increasing attention due to their vital roles in infectious inflammation in the past few years. Interestingly, NETs also play important roles in noninfectious conditions, such as rheumatism and cancer. The process of NETs formation can be regulated and the form of cell death accompanied by the formation of NETs is regarded as “NETosis”. A large amount of evidence has confirmed that many stimuli can facilitate the release of NETs from neutrophils. Furthermore, it has been illustrated that NETs promote tumor growth and progression via many molecular pathways. Meanwhile, NETs also can promote metastasis in many kinds of cancers based on multiple studies. In addition, some researchs have found that NETs can promote coagulation and cancer-associated thrombosis. In the present review, it will highlight how NETosis, which is stimulated by various stimuli and signaling pathways, affects cancer biological behaviors via NETs. Given their crucial roles in cancer, NETs will become possible therapeutic targets for inhibiting proliferation, metastasis and thrombosis in cancer patients.

Abstract Altered metabolic patterns in tumor cells not only meet their own growth requirements but also shape an immunosuppressive microenvironment through multiple mechanisms. Noncoding RNAs constitute approximately 60% of the transcriptional output of human cells and have been shown to regulate numerous cellular processes under developmental and pathological conditions. Given their extensive action mechanisms based on motif recognition patterns, noncoding RNAs may serve as hinges bridging metabolic activity and immune responses. Indeed, recent studies have shown that microRNAs, long noncoding RNAs and circRNAs are widely involved in tumor metabolic rewiring, immune cell infiltration and function. Hence, we summarized existing knowledge of the role of noncoding RNAs in the remodeling of tumor metabolism and the immune microenvironment, and notably, we established the TIMELnc manual, which is a free and public manual for researchers to identify pivotal lncRNAs that are simultaneously correlated with tumor metabolism and immune cell infiltration based on a bioinformatic approach.

Fluorescence imaging-guided surgery is one of important techniques to realize precision surgery. Although second near-infrared window (NIR-II) fluorescence imaging has the advantages of high resolution and large penetration depth in surgical navigation, its major drawback is that NIR-II images cannot be detected by our naked eyes, which demands a high hand-eye coordination for surgeons and increases the surgical difficulty. On the contrary, visible fluorescence can be observed by our naked eyes but has poor penetration. Here, we firstly propose a kind of NIR-II and visible fluorescence hybrid navigation surgery assisted via a cocktail of aggregation-induced emission nanoparticles (AIE NPs). NIR-II imaging helps to locate deep targeted tissues and judge the residual, and visible fluorescence offers an easily surgical navigation. We apply this hybrid navigation mode in different animals and systems, and verify that it can accelerate surgical process and compatible with a visible fluorescence endoscopy. To deepen the understanding of lymph node (LN) labelling, the distribution of NPs in LNs after local administration is initially analyzed by NIR-II fluorescence wide-filed microscopy, and two fates of the NPs are summarized. An alternative strategy which combines indocyanine green and berberine is also reported as a compromise for rapidly clinical translation.

BackgroundAlthough enhanced external counter pulsation (EECP) has been included in the cardiac rehabilitation prescription for coronary heart disease (CHD) in China, because the total treatment duration of a course of EECP is 36–36 h, the average hospital stay of CHD patients is short, and the adherence after discharge remains unclear. The purpose of this study is to investigate the adherence to EECP in CHD patients after discharge, and analyze the related influencing factors.MethodsA retrospective mixed method study combining qualitative and quantitative methods. Quantitative component included CHD patients who had received EECP treatment between March 2020 and August 2021. The qualitative component included in-depth interviews with patients who did not adhere to EECP after discharge. Binary Logistic regression was used to analyze the predictors of EECP adherence after discharge. In-depth interviews with patients were conducted to explore the reasons for dropping out of the EECP after discharge.ResultsAmong 1,304 patients, only 24.23% adhered to EECP treatment after discharge. Binary logistic regression results showed that patients with disease duration < 2 years (OR = 3.13, 95%CI: 2.31–4.24), high school or below (OR = 2.81, 95%CI: 1.98–4.01), distance between residence and hospital more than 20km (OR = 2.08, 95%CI: 1.47–2.96), age over 60 (OR = 2.00, 95%CI: 1.46–2.74), female (OR = 1.64, 95%CI: 1.78–2.29), and angina pectoris (OR = 1.65, 95%CI: 1.16–2.34) were more likely to not adhere to EECP treatment after discharge. However, patients with monthly family income over 8000¥ (OR = 0.46, 95%CI: 0.28–0.75) were more likely to adhere to EECP treatment after discharge than those with household monthly income below 4,000¥. In the qualitative results, the reasons why patients do not adhere to EECP after discharge mainly include insufficient understanding, restricted objective conditions and psychosocial factors.ConclusionsThe adherence of CHD patients to EECP treatment after discharge was poor. It is necessary to develop effective intervention measures, such as brochures or videos to improve patients' understanding of the importance of adherence to EECP treatment after discharge. In addition, offering EECP treatment during off-hours and weekends may also improve adherence in more young patients.

Obesity is often regarded as a factor that promotes tumorigenesis, but the role of obesity in promoting hepatocellular carcinoma (HCC) is still controversial. We compared the trend change of 14 obesity-related genes in the formation and development of HCC in normal, adjacent, and HCC tissues. Mendelian randomization (MR) analysis was used to verify the relationship between obesity and HCC occurrence. Metabolism of cobalamin-associated A (MMAA) was discovered as an obesity- and metabolism-differential gene, and its function in HCC was tested in vitro and in vivo. Finally, we explored how obese female patients with an originally high expression of female estrogen receptor (ESR1) directly upregulated MMAA to interfere with the progression of HCC. Fourteen obesity-related genes were downregulated in adjacent and tumoral tissues compared with normal liver tissues, which indicated that obesity may be inversely related to the occurrence of HCC and was consistent with the results of MR analysis. We also discovered that MMAA is a metabolic gene closely related to the occurrence and development of HCC by mining the TCGA database, and it functioned an anti-tumor-promoting role in HCC by damaging the mitochondrial function and preserving the redox balance. We further verified that obese females with a high expression of ESR1 can regulate MMAA to protect HCC from progression. This study elucidates that obesity might be a protective factor for female HCC patients, as they originally highly expressed ESR1, which could upregulate MMAA to suppress tumor growth and participate in metabolic reprogramming.

Lipids are involved in both energy metabolism and signaling transduction. Abnormal lipid metabolism in T cells is associated with the differentiation, longevity and activity of T cells, which has received increasing concern since its firstly reported in 1985. To evaluate the trends of lipid metabolism in T cells and map knowledge structure, we employed bibliometric analysis. A total of 286 related publications obtained from the Web of Science Core Collection published between 1985 and 2022 were analyzed using indicators of publication and citation metrics, countries, institutes, authors, cited references and key words. The present research status, the global trends and the future development directions in lipid metabolism and T cells were visualized and discussed. In summary, this study provides a comprehensive display on the field of lipid metabolism in T cells, which will help researchers explore lipid metabolism in T cells more effectively and intuitively.

The microbiota is present in many parts of the human body and plays essential roles. The most typical case is the occurrence and development of cancer. Pancreatic cancer (PC), one of the most aggressive and lethal types of cancer, has recently attracted the attention of researchers. Recent research has revealed that the microbiota regulates PC carcinogenesis via an altered immune response. Specifically, the microbiota, in several sites, including the oral cavity, gastrointestinal tract, and pancreatic tissue, along with the numerous small molecules and metabolites it produces, influences cancer progression and treatment by activating oncogenic signaling, enhancing oncogenic metabolic pathways, altering cancer cell proliferation, and triggering chronic inflammation that suppresses tumor immunity. Diagnostics and treatments based on or in combination with the microbiota offer novel insights to improve efficiency compared with existing therapies.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers. It is characterized by stromal richness, lack of blood supply and special metabolic reprogramming in the tumor microenvironment, which is difficult to treat and easy to metastase. Great efforts have been made to develop new drugs which can pass through the stroma and are more effective than traditional chemotherapeutics, such as ferroptosis inducers–Erastin and RSL-3. As current anti-angiogenic therapy drugs alone are suboptimal for PDAC, novel vascular disruption agents in combination with ferroptosis inducers might provide a possible solution. Here, we designed human platelet vesicles (PVs) to camouflage RSL-3 to enhance drug uptake rate by tumor cells and circulation time in vivo, deteriorating the tumor vessels and resulting in tumor embolism to cut the nutrient supply as well as causing cell death due to excessive lipid peroxidation. The RSL-3@PVs can also cause the classic ferroptosis-related change of mitochondrial morphology, with changes in cellular redox levels. Besides that, RSL-3@PVs has been proved to have great biological safety profile in vitro and in vivo. This study demonstrates the promising potential of integrating PVs and RSL-3 as a combination therapy for improving the outcome of PDAC.

Abstract Aggregation‐induced emission (AIE) is a photophysical phenomenon that a certain group of luminescent materials that become highly luminous when aggregated in a bad solvent or solid state. This year is the 20th anniversary since the AIE concept firstly proposed in 2001. Many advanced applications were gradually being explored, covering optics, electronics, energy, and bioscience and so on. At present, bibliometrics can enlighten the researchers with comprehensive sights of the achievements and trends of a specific field, which is critical for academic investigations. Herein, we presented a general bibliometric overview of AIE covering 20 years of evolution. With the assistance of Web of Science Core Collection database and several bibliometric software tools, the annual publication and citation, most influential countries/regions, most contributing authors, journals and institutions, second near‐infrared (NIR‐II) related hotspots, as well as the forecast of frontiers were demonstrated and systematically analyzed. This study summarizes the current research status in AIE research field and provides a reference for future research directions.

PurposeThis clinical study sought to determine whether the levels of inflammatory markers predicted the survival of advanced gastric cancer (AGC) patients who underwent anti-programmed death 1 (PD-1) therapy.MethodsUsing AGC patient plasma samples and baseline characteristics, we investigated the specific value of inflammatory markers in AGC from a clinical perspective in immunotherapy.ResultsOne hundred and six patients with AGC who underwent anti-PD-1 therapy were enrolled in this study between 20 July 2019 and 16 March 2021. A significant decrease in NLR, dNLR, and SII was noticed among the PR (P=0.023; P=0.036; P=0.001), SD (P=0.048; P=0.022; P=0.023), ORR (P=0.021; P=0.032; P=0.001), and DCR (P=0.003; P=0.001; P

The clinical management of patients with COVID-19 and cancer is a Gordian knot that has been discussed widely but has not reached a consensus. We introduced two-sample Mendelian randomization to investigate the causal association between a genetic predisposition to cancers and COVID-19 susceptibility and severity. Moreover, we also explored the mutation landscape, expression pattern, and prognostic implications of genes involved with COVID-19 in distinct cancers. Among all of the cancer types we analyzed, only the genetic predisposition to lung adenocarcinoma was causally associated with increased COVID-19 severity (OR = 2.93, β = 1.074, se = 0.411, p = 0.009) with no obvious heterogeneity (Q = 17.29, p = 0.24) or symmetry of the funnel plot. In addition, the results of the pleiotropy test demonstrated that instrument SNPs were less likely to affect COVID-19 severity via approaches other than lung adenocarcinoma cancer susceptibility (p = 0.96). Leave-one-out analysis showed no outliers in instrument SNPs, whose elimination rendered alterations in statistical significance, which further supported the reliability of the MR results. Broad mutation and differential expression of these genes were also found in cancers, which may provide valuable information for developing new treatment modalities for patients with both cancer and COVID-19. For example, ERAP2, a risk factor for COVID-19-associated death, is upregulated in lung squamous cancer and negatively associated with patient prognosis. Hence, ERAP2-targeted treatment may simultaneously reduce COVID-19 disease severity and restrain cancer progression. Our results highlighted the importance of strengthening medical surveillance for COVID-19 deterioration in patients with lung adenocarcinoma by showing their causal genetic association. For these patients, a delay in anticancer treatment, such as chemotherapy and surgery, should be considered.

By 2050, it is estimated that 10 million people will die of drug-resistant bacterial infection caused by antibiotic abuse. Antimicrobial peptide (AMP) is widely used to prevent such circumstances, for the positively charged AMPs can kill drug-resistant bacteria by destroying negatively charged bacterial cell membrane, and has excellent antibacterial efficiency and low drug resistance. However, due to the defects in low in vivo stability, easy degradation, and certain cytotoxicity, its practical clinical application is limited. The emergence of peptide–polymer conjugates (PPC) helps AMPs overcome these shortcomings. By combining with functional polymers, the positive charge of AMPs is partially shielded, and its stability and water solubility are improved, so as to prolong the in vivo circulation time of AMPs and reduce its cytotoxicity. At the same time, the self-assembly ability of PPC enables it to assemble into different nanostructures to undertake specific antibacterial tasks. At present, PPC is mainly used in wound dressing, bone tissue repair, antibacterial coating of medical devices, nerve repair, tumor treatment, and oral health maintenance. In this study, we summarize the structure, synthesis methods, and the clinical applications of PPC, so as to present the current challenges and discuss the future prospects of antibacterial therapeutic materials.

Introduction: Parkinson's disease (PD) is a common neurodegenerative disease that seriously impairs patients' quality of life, and increases the burden of patients and caregivers. Both drugs and exercise can alleviate its motor and non-motor symptoms, improving the quality of life for PD patients. Telehealth, an increasingly popular tool, makes rehabilitation accessible at home, overcoming the inconvenience of traffic and scheduling. Care-PD is a phone application designed for rehabilitation training, which provides Tai Chi and stretching exercises through tutorial videos as well as an online evaluation system. In this protocol, we will explore the efficacy of Tai Chi and stretching exercises as a PD rehabilitation therapy based on the smartphone application Care-PD.Methods and Analysis: A double-blind, parallel randomized controlled trial will be conducted in this study. The recruitment, intervention, and evaluation processes will be implemented through the Care-PD application. Persons with PD will fill out questionnaires on Activities of Daily Living (ADL), upload the latest case report, and sign the informed consent form in the application. Afterward, doctors and researchers will screen and enroll 180 participants who will be randomly (1:1:1) assigned to Tai Chi group, stretching exercises group, or control group. The subjects will participate in a 1-h exercise session three times per week for 12 weeks, ending with another 4 weeks of follow-up study. Each exercise session includes 10 min of warm-up, 45 min of exercise, and 5 min of cool-down. The primary outcomes are Motor Aspects of Experiences of Daily Living and the 39-item Parkinson's disease Questionnaire. The secondary outcomes include the 9-item Wearing-Off Questionnaire, the Freezing of Gait Questionnaire, the Caregiver Strain Index, Non-motor Experiences of Daily Living, ADL, and Morse Fall Scale. All assessments will be performed at baseline, week 12 and 16.Discussion: Care-PD integrates subject recruitment, intervention, and evaluation, providing a new perspective on clinical rehabilitation for persons with PD. This study will evaluate the efficacy of Tai Chi and stretching exercises on patients' quality of life and disease progression based on a smartphone application. We aim to provide a new rehabilitation training platform for persons with PD.Ethics and Dissemination: This study was approved by the Scientific Research Ethics Committee (102772020RT132) of Shanghai University of Sport. Data collection begins after the approval of the ethics committee. The participants must sign an informed consent form before enrollment. The results will be published in relevant journals, seminars, and be disseminated among rehabilitation practitioners and patients with PD.Clinical Trial Registration: Chinese Clinical Trial Registry, identifier [ChiCTR2100042096]. Registered on January 13, 2021.

Background: The ongoing coronavirus disease (COVID-19) outbreak has placed the healthcare system and student training under considerable pressure. However, the plights of healthcare students in the COVID-19 period have drawn limited attention in China.Methods: A cross-sectional on-line survey was undertaken between January and March 2020 to explore the COVID-19 knowledge, attitude, and practice (KAP) survey among Chinese healthcare students. Demographic information and data on KAP were obtained using a self-reported questionnaire. The percentage KAP scores were categorized as good or poor. Independent predictors of good knowledge of COVID-19 were ascertained to use a logistic regression model.Results: Of the 1,595 participants, 85.9% (1,370) were women, 53.4% were junior college students, 65.8% majoring in nursing, and 29.8% had received training on COVID-19. The overall median percentage for good KAP was 51.6% with knowledge of 28.3%, attitude 67.8%, and practice 58.6%, respectively. Independent predictors of good knowledge of COVID-19 were being students ≥25 (95% CI = 0.27–0.93, P = 0.02), those taking bachelor degrees (95% CI = 1.17–2.07, P = 0.00), and those having participated in COVID-19 treatment training.Conclusions: The result of this study revealed suboptimal COVID-19-related KAP among healthcare students in China. To effectively control future outbreaks of COVID-19, there is a need to implement public sensitization programs to improve the understanding of COVID-19 and address COVID-19-related myths and misconceptions, especially among healthcare students.

Abstract Pancreatic cancer is a highly lethal disease with a poor prognosis, and existing therapies offer only limited effectiveness. Mutation gene sequencing has shown several gene associations that may account for its carcinogenesis, revealing a promising research direction. Poly (ADP-ribose) polymerase (PARP) inhibitors target tumor cells with a homologous recombination repair (HRR) deficiency based on the concept of synthetic lethality. The most prominent target gene is BRCA, in which mutations were first identified in breast cancer and ovarian cancer. PARP inhibitors can trap the PARP-1 protein at a single-stranded break/DNA lesion and disrupt its catalytic cycle, ultimately leading to replication fork progression and consequent double-strand breaks. For tumor cells with BRCA mutations, HRR loss would result in cell death. Pancreatic cancer has also been reported to have a strong relationship with BRCA gene mutations, which indicates that pancreatic cancer patients may benefit from PARP inhibitors. Several clinical trials are being conducted and have begun to yield results. For example, the POLO (Pancreatic Cancer Olaparib Ongoing) trial has demonstrated that the median progression-free survival was observably longer in the olaparib group than in the placebo group. However, PARP inhibitor resistance has partially precluded their use in clinical applications, and the major mechanism underlying this resistance is the restoration of HRR. Therefore, determining how to use PARP inhibitors in more clinical applications and how to avoid adverse effects, as well as prognosis and treatment response biomarkers, require additional research. This review elaborates on future prospects for the application of PARP inhibitors in pancreatic cancer.

Abstract Background Galectins constitute a family of β-galactoside-binding proteins, which influence various hallmarks of pancreatic cancer, including cell proliferation, invasion and migration; immune escape; and angiogenesis. Although many studies have concentrated on the role of galectins in pancreatic cancer, the results remain controversial. Hence, we performed a comprehensive meta-analysis to clarify the precise diagnostic and prognostic value of galectins in pancreatic cancer. Methods PubMed/MEDLINE, EMBASE and Web of Science were used to search related published literature up to July 2019. Pooled hazard ratios (HRs), diagnostic accuracy variables and related 95% confidence intervals (CIs) were calculated using STATA 14.0 software. Results Eleven studies including 1227 participants met our inclusion criteria. High expression of galectin family was not correlated with overall survival (OS) in pancreatic cancer (HR, 1.19; 95% CI 0.67–2.11). According to subgroup analysis, high levels of galectin-1 were significantly correlated with worse OS in pancreatic cancer (HR, 4.77; 95% CI 2.47–9.21), while high levels of tandem-repeat galectins (galectin-4 or galectin-9) predicted both better OS (HR, 0.63; 95% CI 0.46–0.86) and disease-free survival (DFS) (HR, 0.63; 95% CI 0.48–0.83). The expression levels of galectin-3 did not directly correlate with prognosis (HR, 0.99; 95% CI 0.40–2.46). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratios of galectin-3 were 0.64 (95% CI 0.41–0.82), 0.76 (95% CI 0.59–0.88), 2.70 (95% CI 1.21–6.1), and 0.47 (95% CI 0.23–0.98), respectively. The area under the curve (AUC) of galectin-3 was 0.77. Conclusion Taken together, our results suggest that high expression of galectin-1 and low levels of galectin-4 or galectin-9 are predictors of worse prognosis in pancreatic cancer patients. The expression of galectin-3 was not directly related to OS and other clinical characteristics. Although galectin-3 exhibited some diagnostic value in patients with pancreatic cancer in this meta-analysis, clinical application prospects remain to be validated. Further studies are warranted to confirm and strengthen these findings.

Abstract Background Programmed cell death protein 1 (PD-1) is a key immune checkpoint that regulates peripheral tolerance and protects against autoimmunity. Programmed death ligand-2 (PD-L2) is a less studied ligand to PD-1 and has yet to be fully explored, especially in pancreatic ductal adenocarcinoma (PDAC). Methods In this study, we performed immunohistochemistry to detect the PD-L2, CD3, CD8, transforming growth factor-β2 (TGF-β2) and FOXP3 levels in paraffin sections from 305 patients with resected PDAC as a training set. Expression levels of intratumoral and stromal immune markers were compared in relation to survival using Kaplan-Meier curves, random survival forest model and survival tree analysis. A multivariable Cox proportional-hazards model of associated markers was used to calculate the risk scores. Results PD-L2 was expressed in 71.5% of PDAC samples and showed strong correlations with CD3+, CD8+ T cells and FOXP3+ regulatory T cell densities. High levels of intratumoral PD-L2 and FOXP3 were related to poor survival; only stromal FOXP3 overexpression was associated with worse prognosis. Four patterns generated from survival tree analysis demonstrated that PD-L2low stromalFOXP3low patients had the longest survival, while PD-L2high intratumoralCD3low patients had the shortest survival (P

The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.

ObjectiveTo evaluate the reporting quality of randomized controlled trials (RCTs) regarding patients with COVID-19 and analyse the influence factors.MethodsPubMed, Embase, Web of Science and the Cochrane Library databases were searched to collect RCTs regarding patients with COVID-19. The retrieval time was from the inception to December 1, 2020. The CONSORT 2010 statement was used to evaluate the overall reporting quality of these RCTs.Results53 RCTs were included. The study showed that the average reporting rate for 37 items in CONSORT checklist was 53.85% with mean overall adherence score of 13.02±3.546 (ranged: 7 to 22). The multivariate linear regression analysis showed the overall adherence score to the CONSORT guideline was associated with journal impact factor (P = 0.006), and endorsement of CONSORT statement (P = 0.014).ConclusionAlthough many RCTs of COVID-19 have been published in different journals, the overall reporting quality of these articles was suboptimal, it can not provide valid evidence for clinical decision-making and systematic reviews. Therefore, more journals should endorse the CONSORT statement, authors should strictly follow the relevant provisions of the CONSORT guideline when reporting articles. Future RCTs should particularly focus on improvement of detailed reporting in allocation concealment, blinding and estimation of sample size.

Background Pancreatic adenocarcinoma (PAAD) is among the most lethal diseases and has a dismal prognosis; however, efficient treatment is currently limited. Several studies have observed epigenetic variation during tumorigenesis, suggesting the potential role of RNA methylation, especially N6-methyladenosine (m6A) modification, as a novel epigenetic modification mediating PAAD prognosis. Methods The expression levels of m6A-related genes were downloaded from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA) and Genotype-Tissue Expression (GTEx) projects, and the findings were validated in four Expression Omnibus (GEO) datasets. A predictive model was constructed using a lasso regression and evaluated by a survival analysis and receiver operating characteristic curve. Consensus clustering identified two distinct subgroups with different immune activity signatures based on the expression pattern of m6A-related genes. The relationship between the mutation state of m6A-related genes and infiltration of immune cells was established and visualized using Tumor Immune Estimation Resource (https://cistrome.shinyapps.io/timer/). Results Fourteen of twenty-one m6A-related genes were differentially expressed between PAAD and normal tissues in TCGA-GTEx cohort. Among these genes, HNRNPC, IGF2BP2 and YTHDF1 were further validated in four GEO datasets. Moreover, an m6A-based model exhibited moderate accuracy in predicting overall survival in PAAD samples. Additionally, potential m6A modification targets were screened by selecting genes from a set of 23,391 genes that not only harbored the most m6A-modified sites but also showed a robust correlation with PAAD survival. Moreover, we correlated the expression level of m6A-related genes with the immune microenvironment of pancreatic cancer for the first time. Specifically, both arm-level gain and deletion of ALKBH5 decreased the infiltration of CD8+T cells (P

Neutrophils are a significant population of infiltrated immune cells in the tumor microenvironment. Neutrophil extracellular traps (NETs) are implicated in the biological behavior of many malignant tumors. NETs can be degraded into soluble nucleosomes, leading to the release of fragments containing DNA and granule proteins into the peripheral blood (PB). Using human gastric cancer (GC) biopsies and PB samples, we investigated the specific value of NETs in GC from a clinical perspective. In summary, the formation of NETs was discovered in the tissue microenvironment and PB of GC patients. The amounts of NETs and neutrophil accumulation decreased from tumor tissue to paratumor tissue. In addition, the level of NETs in the PB gradually declined through the following patient populations: advanced disease patients, preoperative patients, postoperative patients, benign disease patients, and healthy controls. The levels of NETs in the plasma and serum were significantly correlated. As a serum biomarker, NETs had a better diagnostic value than carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in GC. The neutrophil count and neutrophil to lymphocyte ratio (NLR) were significantly associated with the level of NETs in the PB. The existence of lymph node metastasis indicated a high level of NETs in the serum. Moreover, the level of NETs in the PB was inversely correlated with short-term efficacy in GC patients who had received advanced first-line treatment. The higher baseline level of NETs in the PB of patients with negative HER2 status was correlated with worse progression-free survival (PFS). And the level of NETs in the PB was a unfavorable independent prognostic factor for PFS in patients with advanced GC who had received first-line treatment. Thus, NETs have novel diagnostic, therapeutic predictive, and prognostic value in GC patients.

Abstract A poor prognosis of pancreatic ductal adenocarcinoma (PDAC) associated with chemoresistance has not changed for the past three decades. A multidisciplinary diagnosis followed by surgery and chemo(radiation)therapy is the main treatment approach. However, gemcitabine- and 5-fluorouracil-based therapies did not present satisfying outcomes. Novel regimens targeting pancreatic cancer cells, the tumor microenvironment, and immunosuppression are emerging. Biomarkers concerning the treatment outcome and patient selection are being discovered in preclinical or clinical studies. Combination therapies of classic chemotherapeutic drugs and novel agents or novel therapeutic combinations might bring hope to the dismal prognosis for PDAC patients.

Quorum sensing (QS) is a cell density-dependent mechanism that regulates the expression of specific genes in microbial cells. Quorum quenching (QQ) is a promising strategy for attenuating pathogenicity by interfering with the QS system of pathogens. N-Acyl-homoserine lactones (AHLs) act as signaling molecules in many Gram-negative bacterial pathogens and have received wide attention. In this study, a novel, efficient AHL-degrading bacterium, Acinetobacter sp. strain XN-10, was isolated from agricultural contaminated soil and evaluated for its degradation efficiency and potential use against QS-mediated pathogens. Strain XN-10 could effectively degrade N-(3-oxohexanoyl)-L-homoserine lactone (OHHL), N-hexanoyl-L-homoserine lactone (C6HSL), N-(3-oxododecanoyl)-L-homoserine lactone (3OC12HSL), and N-(3-oxooctanoyl)-L-homoserine lactone (3OC8HSL), which all belong to the AHL family. Analysis of AHL metabolic products by gas chromatography–mass spectrometry (GC-MS) led to the identification of N-cyclohexyl-propanamide, and pentanoic acid, 4-methyl, methyl ester as the main intermediate metabolites, revealing that AHL could be degraded by hydrolysis and dehydroxylation. All intermediates were transitory and faded away without any non-cleavable metabolites at the end of the experiment. Furthermore, strain XN-10 significantly attenuated the pathogenicity of Pectobacterium carotovorum subsp. carotovorum (Pcc) to suppress tissue maceration in carrots, potatoes, and Chinese cabbage. Taken together, our results shed light on the QQ mechanism of a novel AHL-degrading bacterial isolate, and they provide useful information which show potential for biocontrol of infectious diseases caused by AHL-dependent bacterial pathogens.

Objective Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.Design Literature review, pooling analysis and correlation analysis.Data sources PubMed, from 1 January 2010 to 30 June 2017.Eligibility criteria for selecting studies Eligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.Results Of 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p