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Abstract The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan–Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03–3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.

Abstract Panax notoginseng saponins (PNS) are the main active components of Panax notoginseng. But after oral administration, they need to be converted into rare ginsenosides by human gut microbiota and gastric juice before they can be readily absorbed into the bloodstream and exert their effects. The sources of rare ginsenosides are extremely limited in P. notoginseng and other medical plants, which hinders their application in functional foods and drugs. Therefore, the production of rare ginsenosides by the transformation of PNS using Aspergillus fumigatus was studied in this research. During 50 days at 25 ℃ and 150 rpm, A. fumigatus transformed PNS to 14 products (1–14). They were isolated by varied chromatographic methods, such as silica gel column chromatography, Rp-C18 reversed phase column chromatography, semi-preparative HPLC, Sephadex LH-20 gel column chromatography, and elucidated on the basis of their 1H-NMR, 13C-NMR and ESIMS spectroscopic data. Then, the transformed products (1–14) were isolated and identified as Rk3, Rh4, 20 (R)-Rh1, 20 (S)-Protopanaxatriol, C-K, 20 (R)-Rg3, 20 (S)-Rg3, 20 (S)-Rg2, 20 (R)-R2, Rk1, Rg5, 20 (S)-R2, 20 (R)-Rg2, and 20 (S)-I, respectively. In addition, all transformed products (1–14) were tested for their antimicrobial activity. Among them, compounds 5 (C-K) and 7 [20 (S)-Rg3] showed moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 6.25, 1.25 μg/mL and 1.25, 25 μg/mL, respectively. This study lays the foundation for production of rare ginsenosides. Graphical abstract

To investigate the effects of Angel yeast, Meyerozyma guilliermondii, Saccharomyces cerevisiae, Zygosaccharomyces rouxii and Candida parapsilosis fermentation on volatile flavour compounds in bean paste, the volatile flavour substances of fermented bean soup paste were analyzed by gas chromatography-ion mobility spectrometry (GC-IMS) technique using unfermented bean soup paste as a control group. The relative odour activity value (ROAV) method was used to determine the key flavour components. Principal component analysis (PCA) and partial least squares-discrimination analysis (PLS-DA) were used to comprehensively evaluate the aroma of fermented bean soup paste. A total of 50 volatile compounds were identified, which were primarily esters and alcohols in six fermented bean sauces. These compounds contribute to the distinct mellow, fruity, and malty flavour profiles characteristic of these sauces. The types and concentrations of volatile compounds in different fermented bean sauces exhibited statistically significant differences (P

Cooking methods could have a great influence on the flavour of food, to investigate the effect of cooking methods on the aroma of pork, this study used electronic nose combined with gas chromatography-ion mobility spectrometry (GC-IMS) for multivariate statistical analyses of the volatile compounds in pork under different cooking methods. GC-IMS was used to characterise 100 volatile compounds (including monomers and dimers) of pork under different cooking methods. Finally, a stable model was established using orthogonal partial least squares discriminant analysis. Results showed that, the cooking method is crucial for the formation of pork flavour compounds. Pork cooked by oven roasting and air fryer methods contained characteristic volatile compounds such as ethyl (E)-2-hexenoate, 1-octen-3-ol, (Z)-4-decenal, 3-nonen-2-one, (E)-2-hexen-1-ol, propyl butyrate, furazanone, and dipentenyl-M, as compared to the two cooking methods of steaming and boiling. The air fryer method pork contained higher levels of (E)-ethyl 2-hexenoate, 1-octen-3-ol, (Z)-4-decenal, and 3-nonen-2-one than the oven-roasted pork. Valeraldehyde and ethyl acetate were labelled as characteristic volatile substance compounds for both steamed and boiled cooking styles, and the results from the electronic nose sensor showed that the RPCA model was effective in identifying volatile substances in pork for each cooking style. The results of the study revealed the effects of different cooking methods on the volatile components of pork and found that the aromas of air fryer preparation and oven roasting were more similar, providing some reference for the cooking and processing of pork.

Abstract The generation of radiological results from image data represents a pivotal aspect of medical image analysis. The latest iteration of ChatGPT-4, a large multimodal model that integrates both text and image inputs, including dermatoscopy images, histology images, and X-ray images, has attracted considerable attention in the field of radiology. To further investigate the performance of ChatGPT-4 in medical image recognition, we examined the ability of ChatGPT-4 to recognize credible osteosarcoma X-ray images. The results demonstrated that ChatGPT-4 can more accurately diagnose bone with or without significant space-occupying lesions but has a limited ability to differentiate between malignant lesions in bone compared to adjacent normal tissue. Thus far, the current capabilities of ChatGPT-4 are insufficient to make a reliable imaging diagnosis of osteosarcoma. Therefore, users should be aware of the limitations of this technology.

Abstract Background Deuterium metabolic imaging (DMI) has emerged as a promising non-invasive technique for studying metabolism in vivo. This review aims to summarize the current developments and discuss the futures in DMI technique in vivo. Methods A systematic literature review was conducted based on the PRISMA 2020 statement by two authors. Specific technical details and potential applications of DMI in vivo were summarized, including strategies of deuterated metabolites detection, deuterium-labeled tracers and corresponding metabolic pathways in vivo, potential clinical applications, routes of tracer administration, quantitative evaluations of metabolisms, and spatial resolution. Results Of the 2,248 articles initially retrieved, 34 were finally included, highlighting 2 strategies for detecting deuterated metabolites: direct and indirect DMI. Various deuterated tracers (e.g., [6,6′-2H2]glucose, [2,2,2′-2H3]acetate) were utilized in DMI to detect and quantify different metabolic pathways such as glycolysis, tricarboxylic acid cycle, and fatty acid oxidation. The quantifications (e.g., lactate level, lactate/glutamine and glutamate ratio) hold promise for diagnosing malignancies and assessing early anti-tumor treatment responses. Tracers can be administered orally, intravenously, or intraperitoneally, either through bolus administration or continuous infusion. For metabolic quantification, both serial time point methods (including kinetic analysis and calculation of area under the curves) and single time point quantifications are viable. However, insufficient spatial resolution remains a major challenge in DMI (e.g., 3.3-mL spatial resolution with 10-min acquisition at 3 T). Conclusions Enhancing spatial resolution can facilitate the clinical translation of DMI. Furthermore, optimizing tracer synthesis, administration protocols, and quantification methodologies will further enhance their clinical applicability. Relevance statement Deuterium metabolic imaging, a promising non-invasive technique, is systematically discussed in this review for its current progression, limitations, and future directions in studying in vivo energetic metabolism, displaying a relevant clinical potential. Key points • Deuterium metabolic imaging (DMI) shows promise for studying in vivo energetic metabolism. • This review explores DMI’s current state, limits, and future research directions comprehensively. • The clinical translation of DMI is mainly impeded by limitations in spatial resolution. Graphical Abstract

Abstract Background Studies have revealed the effects of childhood adversity, anxiety, and negative coping on sleep quality in older adults, but few studies have focused on the association between childhood adversity and sleep quality in rural older adults and the potential mechanisms of this influence. In this study, we aim to evaluate sleep quality in rural older adults, analyze the impact of adverse early experiences on their sleep quality, and explore whether anxiety and negative coping mediate this relationship. Methods Data were derived from a large cross-sectional study conducted in Deyang City, China, which recruited 6,318 people aged 65 years and older. After excluding non-agricultural household registration and lack of key information, a total of 3,873 rural older adults were included in the analysis. Structural equation modelling (SEM) was used to analyze the relationship between childhood adversity and sleep quality, and the mediating role of anxiety and negative coping. Results Approximately 48.15% of rural older adults had poor sleep quality, and older adults who were women, less educated, widowed, or living alone or had chronic illnesses had poorer sleep quality. Through structural equation model fitting, the total effect value of childhood adversity on sleep quality was 0.208 (95% CI: 0.146, 0.270), with a direct effect value of 0.066 (95% CI: 0.006, 0.130), accounting for 31.73% of the total effect; the total indirect effect value was 0.142 (95% CI: 0.119, 0.170), accounting for 68.27% of the total effect. The mediating effects of childhood adversity on sleep quality through anxiety and negative coping were significant, with effect values of 0.096 (95% CI: 0.078, 0.119) and 0.024 (95% CI: 0.014, 0.037), respectively. The chain mediating effect of anxiety and negative coping between childhood adversity and sleep quality was also significant, with an effect value of 0.022 (95% CI: 0.017, 0.028). Conclusions Anxiety and negative coping were important mediating factors for rural older adult’s childhood adversity and sleep quality. This suggests that managing anxiety and negative coping in older adults may mitigate the negative effects of childhood adversity on sleep quality.

Abstract Background Immunotherapy based on the application of immune checkpoint inhibitors (ICIs) is one of the standard treatments for advanced non-small cell lung cancer (NSCLC). Non-alcoholic fatty liver Disease (NAFLD) has demonstrated predictive value for response to immunotherapy in non-lung cancer types. Our study investigated the effect of NAFLD on the efficacy of real-life use of ICIs for patients with stage III / IV NSCLC. Methods The clinical and imaging data of patients with stage III / IV NSCLC who were first admitted to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to July 2022 were retrospectively collected to ensure that they underwent at least one CT scan before treatment. A total of 479 patients were divided into the NAFLD group (Liver/Spleen density ratio ≤ 1) and the non-NAFLD group (Liver/Spleen density ratio > 1) by measuring the baseline liver and spleen CT value. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of the patients were obtained. Results A total of 118 patients with NAFLD and 361 patients without NAFLD were included in the study. Patients with NAFLD tended to have higher BMI and higher total bilirubin compared to patients without NAFLD. The median duration of follow-up in the study was 22 m (IQR, 17–29 m). Both of 2 groups had a higher DCR (94% vs. 92%, p = 0.199) and ORR (38.1% vs. 44.9%, p = 0.452) respectively. There was no difference in efficacy between the two groups. In univariate analysis, NAFLD had no significant effect on PFS (p = 0.785) and OS (p = 0.851). Surprisingly, the presence of hypertension was observed to be associated with a higher OS (HR 1.471 95%CI 1.018–2.127, p = 0.040). Besides, based on multivariate analysis, lactic dehydrogenase was associated with PFS (HR 1.001 95%CI 1.000,1.002, p = 0.037) and OS (HR 1.002, 95%CI 1.001–1.003, p

The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radiofrequency ablation (iRFA) are major reasons for rapid tumor progression and pose challenges for immunotherapy. We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma (HCC) treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival. Using an orthotopic HCC mouse model and a colorectal liver metastasis model, we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best outcomes when combined with anti-programmed death-ligand 1 (anti-PD-L1) therapy. In mechanism, melatonin inhibited the expression of epithelial-mesenchymal transitions, hypoxia-inducible factor (HIF)-1α, and PD-L1 in tumor cells after iRFA. Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+ T cells. Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors. These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation, thereby overcoming the immunosuppressive tumor microenvironment (TME) and enhancing the efficacy of immunotherapy.

BackgroundTemporal bone computed tomography (CT) helps diagnose chronic otitis media (COM). However, its interpretation requires training and expertise. Artificial intelligence (AI) can help clinicians evaluate COM through CT scans, but existing models lack transparency and may not fully leverage multidimensional diagnostic information. ObjectiveWe aimed to develop an explainable AI system based on 3D convolutional neural networks (CNNs) for automatic CT-based evaluation of COM. MethodsTemporal bone CT scans were retrospectively obtained from patients operated for COM between December 2015 and July 2021 at 2 independent institutes. A region of interest encompassing the middle ear was automatically segmented, and 3D CNNs were subsequently trained to identify pathological ears and cholesteatoma. An ablation study was performed to refine model architecture. Benchmark tests were conducted against a baseline 2D model and 7 clinical experts. Model performance was measured through cross-validation and external validation. Heat maps, generated using Gradient-Weighted Class Activation Mapping, were used to highlight critical decision-making regions. Finally, the AI system was assessed with a prospective cohort to aid clinicians in preoperative COM assessment. ResultsInternal and external data sets contained 1661 and 108 patients (3153 and 211 eligible ears), respectively. The 3D model exhibited decent performance with mean areas under the receiver operating characteristic curves of 0.96 (SD 0.01) and 0.93 (SD 0.01), and mean accuracies of 0.878 (SD 0.017) and 0.843 (SD 0.015), respectively, for detecting pathological ears on the 2 data sets. Similar outcomes were observed for cholesteatoma identification (mean area under the receiver operating characteristic curve 0.85, SD 0.03 and 0.83, SD 0.05; mean accuracies 0.783, SD 0.04 and 0.813, SD 0.033, respectively). The proposed 3D model achieved a commendable balance between performance and network size relative to alternative models. It significantly outperformed the 2D approach in detecting COM (P≤.05) and exhibited a substantial gain in identifying cholesteatoma (P

Abstract Background The hospitalization rate of ambulatory care sensitive conditions (ACSCs) has been recognized as an essential indicator reflective of the overall performance of healthcare system. At present, ACSCs has been widely used in practice and research to evaluate health service quality and efficiency worldwide. The definition of ACSCs varies across countries due to different challenges posed on healthcare systems. However, China does not have its own list of ACSCs. The study aims to develop a list to meet health system monitoring, reporting and evaluation needs in China. Methods To develop the list, we will combine the best methodological evidence available with real-world evidence, adopt a systematic and rigorous process and absorb multidisciplinary expertise. Specific steps include: (1) establishment of working groups; (2) generations of the initial list (review of already published lists, semi-structured interviews, calculations of hospitalization rate); (3) optimization of the list (evidence evaluation, Delphi consensus survey); and (4) approval of a final version of China’s ACSCs list. Within each step of the process, we will calculate frequencies and proportions, use descriptive analysis to summarize and draw conclusions, discuss the results, draft a report, and refine the list. Discussion Once completed, China’s list of ACSCs can be used to comprehensively evaluate the current situation and performance of health services, identify flaws and deficiencies embedded in the healthcare system to provide evidence-based implications to inform decision-makings towards the optimization of China’s healthcare system. The experiences might be broadly applicable and serve the purpose of being a prime example for nations with similar conditions.

In order to utilize Lactobacillus casei to prepare fermented pineapple juice beverage, the growth curve, acid production, acid tolerance, and sugar tolerance characteristics of Lactobacillus casei LK-1 (L. casei LK-1) were investigated and analyzed in this research. Moreover, the optimal conditions for the fermentation of pineapple juice by L. casei LK-1 were explored by single-factor test and response surface methodology, with the viable cell count and total acid content as indicators. As revealed by the results, L. casei LK-1 grew and reproduced well in an environment with pH5~7 or containing 0% to 10% glucose. The survival rates of it were 76% and 71%, respectively, after 3 h of incubation in an acidic (pH3) or high sugar (40% glucose) environment. Besides, after 48 h incubation in MRS medium, its acid production was 5.35 g/kg, which was good for the fermentation of the juice. The optimal conditions for fermenting pineapple juice with L. casei LK-1 were: Initial pH of 6.8, fermentation temperature of 37 ℃, inoculum level of 1% (v/v), as well as fermentation time of 30 h. Under this preparation condition, the viable cell count of fermented pineapple juice was 8.99±0.04 lg CFU/mL, the total acid content was 7.16±0.26 g/kg, and the juice was bright in color, sweet and sour with excellent flavor. The results of this research can provide a theoretical and technical basis for the further application of L. casei LK-1 in fermented foods.

Abstract Background Pelvic floor dysfunction (PFD) is an extremely widespread urogynecologic disorder, the prevalence of which increases with aging. PFD has severely affected women’s quality of life and has been called a social cancer. While previous studies have identified risk factors such as vaginal delivery and obesity for PFD, other reproductive factors, including age at menarche (AAMA), have been largely overlooked. Therefore, we used a Mendelian randomization (MR) study for the first time to investigate the potential causal relationship between reproductive factors and PFD. Methods We obtained summary statistics from genome-wide association studies (GWAS) for female genital prolapse (FGP), stress urinary incontinence (SUI), and five reproductive factors. Two-sample Mendelian randomization analysis (TSMR) was performed to explore the causal associations between these factors. The causal effects of reproductive factors on FGP and SUI were primarily estimated using the standard inverse variance weighting (IVW) method, with additional complementary and sensitivity analyses conducted using multiple approaches. A multivariate Mendelian randomization (MVMR) study was also conducted to adjust for pleiotropic effects and possible sources of selection bias and to identify independent exposure factors. Results Our findings revealed that advanced age at first sexual intercourse (AFS) and age at first birth (AFB) exhibited negative causal effects on both FGP and SUI. AAMA showed negative causal effects solely on FGP, while age at last live birth (ALB) and age at menopause (AAMO) did not demonstrate any causal effect on either FGP or SUI. And the MVMR results showed that AFB and AFS had independent negative causal effects on FGP and SUI, respectively. Conclusions This study, for the first time, investigates the causal relationship between reproductive factors and PFD. The results suggested a causal relationship between some reproductive factors, such as AFB and AFS, and PFD, but there were significant differences between FGPand SUI. Therefore, future studies should explore the underlying mechanisms and develop preventive measures for reproductive factors to reduce the disease burden of PFD.

Abstract Background Immune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced disease. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified. Methods Patients diagnosed with stages III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022, were included in this retrospective study. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during non-ECG-gated chest CT scans at baseline and 3, 6, and 12 months after treatment. Propensity score matching (PSM) was performed in a 1:1 ratio to balance the baseline characteristics between the two groups. Results Overall, 1458 patients (487 with ICI therapy and 971 without ICI therapy) were enrolled in this cardiovascular cohort study. After PSM, 446 patients were included in each group. During the entire period of follow-up (median follow-up 23.1 months), 24 atherosclerotic cardiovascular disease (ASCVD) events (4.9%) occurred in the ICI group, and 14 ASCVD events (1.4%) in the non-ICI group, before PSM; 24 ASCVD events (5.4%) occurred in the ICI group and 5 ASCVD events (1.1%) in the non-ICI group after PSM. The CAC imaging study group comprised 113 patients with ICI therapy and 133 patients without ICI therapy. After PSM, each group consisted of 75 patients. In the ICI group, the CAC volume/score increased from 93.4 mm3/96.9 (baseline) to 125.1 mm3/132.8 (at 12 months). In the non-ICI group, the CAC volume/score was increased from 70.1 mm3/68.8 (baseline) to 84.4 mm3/87.9 (at 12 months). After PSM, the CAC volume/score was increased from 85.1 mm3/76.4 (baseline) to 111.8 mm3/121.1 (12 months) in the ICI group and was increased from 74.9 mm3/76.8 (baseline) to 109.3 mm3/98.7 (12 months) in the non-ICI group. Both cardiovascular events and CAC progression were increased after the initiation of ICIs. Conclusions Treatment with ICIs was associated with a higher rate of ASCVD events and a noticeable increase in CAC progression.

Abstract Background Alzheimer's disease (AD) and other forms of dementia are the seventh leading cause of death. Studies discern the inclusion of air pollution among modifiable risk factors for dementia, while limited studies are for China. This study aims to examine the short-term association between airborne particulate matter (PM) and the hospitalizations of AD, including the economic costs in China. Methods A total of 4975 cases of AD patients hospitalized from 2017 to 2019, were collected from nine city and 411 medical institutions in Sichuan Province, China. Data on air pollutants such as PM2.5, PM10, and NO2 were obtained from 183 air quality monitoring stations in Sichuan Province. A time series-generalized additive model was used to estimate the association between short-term exposure to PM (lag1–lag7 and moving average lag01–lag07) and AD hospital admissions (HAs), stratified by gender, age, and season. Results Positive short-term exposure to airborne PM was found for the HAs of AD. The greatest effect on the number of AD inpatients was on single-day lag1 (PM2.5:1.034 (95% confidence interval (CI) 1.011, 1.058)). The association was also significant in the two-pollutant model. In the study period, 16.48% of AD HAs were attributed to the effect of PM. The total economic costs of AD attributable to PM exposure were US$ 2.56 million, including US$ 2.25 million of direct medical costs and US$ 0.31 million of indirect economic costs. Conclusions This study suggests that short-term exposure to airborne PM may increase the risk of AD HAs in Sichuan Province and result in associated economic costs.

Abstract Recently, the efficacy of two low-invasive treatments, ablation, and radiotherapy, has been fully compared for the patients with the early-stage hepatocellular carcinoma (HCC). However, the comparison between radiotherapy plus ablation and ablation alone has been less frequently reported. Data from the Surveillance, Epidemiology, and End Results (SEER) database were searched for early-stage HCC patients treated with ablation plus radiotherapy or ablation alone. The outcome measures were overall survival (OS) and cancer-specific survival (CSS). The propensity score matching (PSM) was used to reduce selection bias. We included 240 and 6619 patients in the radiotherapy plus ablation group and ablation group before the PSM. After PSM, 240 pairs of patients were included. The median OS (mOS) and median CSS (mCSS) of patients receiving ablation alone were longer than that of receiving radiotherapy plus ablation (mOS: 47 vs. 34 months, P = 0.019; mCSS: 77 vs. 40 months, P = 0.018, after PSM) before and after PSM. The multivariate analysis indicated that radiotherapy plus ablation independent risk factor for OS and CSS before PSM, but the significance disappeared after PSM. The detailed subgroup analyses indicated ablation alone brought more benefit in very early-stage HCC and older patients. In addition, we found different types of radiotherapy might lead to different outcomes when combined with ablation. In conclusion, ablation alone is noninferior to radiotherapy plus ablation in patients with early-stage HCC. The additional radiation prior to ablation may bring survival benefits in the patients with higher tumor stage. However, due to the risk of selection bias in that study, the results should be interpreted cautiously.

Herein, graphene with two different average sheet diameters was ultrasonically dispersed, mechanically stirred, and copper-plated. The pretreated graphene was mixed with 6061-aluminum (6061Al) powder to fabricate copper-plated graphene (0.5 wt%) reinforced 6061Al matrix composites by spark plasma sintering. The resulting composites were characterized in terms of their microstructure, tensile properties, electrical conductivity, and thermal conductivity. The incorporation of graphene facilitated load transfer and hindered dislocation movement, thereby enhancing the mechanical properties of the composites. Notably, the composite reinforced by larger-sized graphene achieved a favorable combination of high tensile strength (218 MPa) and fracture strain (17.2 %). Moreover, the addition of graphene also ameliorated the electrical conductivity of 6061Al. The composite reinforced by the larger-sized graphene achieved the highest electrical conductivity of 47.7 %IACS, attributed to the formation of a wider range of conductive channels. Additionally, the introduction of larger-sized graphene increased the thermal conductivity of 6061Al from 161.4 W/(m·K) to 183.2 W/(m·K), whilst the smaller-sized graphene contributed to a modest enhancement of 15.3 W/(m·K). In conclusion, graphene with a larger sheet diameter exhibits a remarkable reinforcement effect on the overall performance of 6061Al.

BackgroundAlthough numerous studies have reported the association between tertiary lymphoid structures (TLSs) and clinical outcomes in cancer patients treated with immune checkpoint inhibitors (ICIs), there remains a lack of a newer and more comprehensive meta-analysis. The main objective of this study is to explore prognostic biomarkers in immunotherapy-related patients, through analyzing the associations between tertiary lymphoid structures (TLSs) and clinical outcomes in cancer patients treated with ICIs, so as to investigate their prognostic value in cancer patients treated with ICIs.MethodsA comprehensive search was conducted until February 2024 across PubMed, Embase, Web of Science, and the Cochrane Library databases to identify relevant studies evaluating the association between tertiary lymphoid structures and clinical outcomes in cancer patients treated with ICIs. The clinical outcomes were overall survival (OS), progression‐free survival (PFS), and objective response rate (ORR).ResultsThirteen studies were incorporated in this meta-analysis, among which nine evaluated the prognostic value of TLSs. The results showed the high levels of TLSs predicted a significantly prolonged OS (pooled HR = 0.35, 95% CI: 0.24–0.53, p

BackgroundImmune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs.MethodsThis study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves.ResultsA total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, P = 0.964; 44.7% vs. 44.7% after PSM, P = 1.000) and DCR (91.1% vs. 94.3% before PSM, P = 0.195; 93.3% vs. 96.7% after PSM, P =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, P = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, P = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, P< 0.001) and after PSM analysis (20.0 months vs. 23.0 months, P = 0.008).ConclusionLower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.

Abstract Background Stress urinary incontinence (SUI) is characterized by involuntary urine leakage in response to increased abdominal pressure, such as coughing, laughing, or sneezing. It significantly affects women’s quality of life and imposes a substantial disease burden. While pregnancy and childbirth have been previously identified as risk factors for SUI, educational attainment may also play a role. Therefore, this paper investigates the causal relationship between educational attainment and SUI using two-sample Mendelian randomization (TSMR) analysis, years of schooling (YOS), and college or university degree (CUD) as proxies. Methods Summary statistics of YOS, CUD, and SUI were obtained from genome-wide association studies (GWAS), and TSMR analysis was applied to explore potential causal relationships between them. Causal effects were mainly estimated using the standard inverse variance weighting (IVW) method, and complementary and sensitivity analyses were also performed using multiple methods. Results The results indicate that both YOS (OR = 0.994, 95% CI: 0.992–0.996; P = 7.764E-10) and CUD (OR = 0.987, 95% CI: 0.983–0.991; P = 1.217E-09) may have a negative causal effect on SUI. Conclusions Improving educational attainment may go some way towards reducing the risk of SUI. Therefore, it is important to increase efforts to improve the imbalance in educational development and safeguard women’s health.

Abstract The immune system is closely associated with the pathogenesis of polycystic ovary syndrome (PCOS). Macrophages are one of the important immune cell types in the ovarian proinflammatory microenvironment, and ameliorate the inflammatory status mainly through M2 phenotype polarization during PCOS. Current therapeutic approaches lack efficacy and immunomodulatory capacity, and a new therapeutic method is needed to prevent inflammation and alleviate PCOS. Here, octahedral nanoceria nanoparticles with powerful antioxidative ability were bonded to the anti-inflammatory drug resveratrol (CeO2@RSV), which demonstrates a crucial strategy that involves anti-inflammatory and antioxidative efficacy, thereby facilitating the proliferation of granulosa cells during PCOS. Notably, our nanoparticles were demonstrated to possess potent therapeutic efficacy via anti-inflammatory activities and effectively alleviated endocrine dysfunction, inflammation and ovarian injury in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Collectively, this study revealed the tremendous potential of the newly developed nanoparticles in ameliorating the proinflammatory microenvironment and promoting the function of granulosa cells, representing the first attempt to treat PCOS by using CeO2@RSV nanoparticles and providing new insights in combating clinical PCOS.

Abstract Diagnosis of aneurysm and possibility of aneurysm rupture are crucial for avoiding brain hemorrhage. In this work, blood stream inside internal carotid arteries (ICAs) are simulated in diverse working conditions to disclose the importance of hemodynamic factors on the rupture of aneurysm. The main attention of this study is to investigate the role of hemodynamic on the aneurysm rupture. Statistical and computational methods are applied to investigate coiling porosity and blood hematocrit in 9 specific real ICA geometries. Response surface model (RSM) develops 25 runs to investigate all features of selected geometrical parameters and treatment factors. Computational fluid dynamic is used for the simulation of the blood stream in the selected aneurysms. The effects of sac section area and mean radius of parent vessel on blood hemodynamics are fully investigated. Hemodynamic factors are examined and compared at the peak systolic time instant, including pressure distributions, and velocity. Achieved results indicate that the increasing sac section area (from 36.6 to 75.4 mm2) results in 20% pressure reduction on the sac wall.

With the deepening of people’s understanding of lung cancer, the research of lung cancer immunotherapy has gradually become the focus of attention. As we all know, the treatment of many diseases relies on the rich sources, complex and varied compositions and wide range of unique biological properties of natural products. Studies have shown that natural products can exert anticancer effects by inducing tumor cell death, inhibiting tumor cell proliferation, and enhancing tumor cell autophagy. More notably, natural products can adjust and strengthen the body’s immune response, which includes enhancing the function of NK cells and promoting the differentiation and proliferation of T lymphocytes. In addition, these natural products may enhance their anticancer effects by affecting inhibitory factors in the immune system, hormone levels, enzymes involved in biotransformation, and modulating other factors in the tumor microenvironment. The importance of natural products in lung cancer immunotherapy should not be underestimated. However, the specific links and correlations between natural products and lung cancer immunity are not clear enough, and further studies are urgently needed to clarify the relationship between the two. In this paper, we will focus on the correlation between natural products and lung cancer immune responses, with a view to providing new research perspectives for immunotherapy of lung cancer.

BackgroundImmunotherapy, represented by immune checkpoint inhibitors (ICIs), is a major breakthrough in cancer treatment. Studies have reported that the use of ICIs is associated with an increase in the pulmonary artery to ascending aorta diameter (PAD/AoD) ratio. However, the impact of PAD/AoD ratio progression on the prognosis of patients is unclear.MethodsThis retrospective cohort study included patients with stage III or IV non-small cell lung cancer (NSCLC) treated with ICIs at the Wuhan Union Hospital between March 1, 2020, and September 1, 2022. The baseline and post-treatment PAD/AoD ratios of patients were evaluated through chest CT scans. The primary outcome of this study was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR).ResultsThe PAD/AoD ratio increased after the initiation of ICIs (from 0.75 to 0.78; P < 0.001). A total of 441 patients were divided into severe group (n=221) and non-severe group (n=220) according to the median increase of PAD/AoD ratio (1.06). Compared with the non-severe group, the severe group had a lower DCR (87.8% vs. 96.0%, P = 0.005) and ORR (87.5% vs. 96.0%, P = 0.063). Over the entire duration of follow-up (median 22.0 months), 85 (38.5%) patients in the severe group and 30 (7.3%) patients in the non-severe group died. An increased PAD/AoD ratio was associated with shorter PFS (Hazard ratio (HR): 1.48 [95% CI, 1.14 to 1.93]; P = 0.003) and OS (HR: 3.50 [95% CI, 2.30 to 5.30]; P < 0.001). Similar results were obtained across subgroups.ConclusionsICI treatment exacerbates an increase in the PAD/AoD ratio in patients with cancer, and greater increase in the PAD/AoD ratio was associated with a worse prognosis. PAD/AoD ratio could be a biomarker to stratify prognosis of NSCLC patients treated with ICIs.

BackgroundThis study aimed to explore the relationship between air pollution and hospital admissions for asthma in older adults, and to further assess the health and economic burden of asthma admissions attributable to air pollution.MethodsWe collected information on asthma cases in people over 65 years of age from nine cities in Sichuan province, as well as air pollution and meteorological data. The relationship between short-term air pollutant exposure and daily asthma hospitalizations was analyzed using the generalized additive model (GAM), and stratified by gender, age, and season. In addition, we assessed the economic burden of hospitalization for air pollution-related asthma in older adults using the cost of disease approach.ResultsThe single pollutant model showed that every 1 mg/m3 increase in CO was linked with an increase in daily hospitalizations for older adults with asthma, with relative risk values of 1.327 (95% CI: 1.116–1.577) at lag7. Each 10 μg/m3 increase in NO2, O3, PM10, PM2.5 and SO2, on asthma hospitalization, with relative risk values of 1.044 (95% CI: 1.011–1.078), 1.018 (95% CI: 1.002–1.034), 1.013 (95% CI: 1.004–1.022), 1.015 (95% CI: 1.003–1.028) and 1.13 (95% CI: 1.041–1.227), respectively. Stratified analysis shows that stronger associations between air pollution and asthma HAs among older adult in females, those aged 65–69 years, and in the warm season, although all of the differences between subgroups did not reach statistical significance. During the study period, the number of asthma hospitalizations attributable to PM2.5, PM10, and NO2 pollution was 764, 581 and 95, respectively, which resulted in a total economic cost of 6.222 million CNY, 4.73 million CNY and 0.776 million CNY, respectively.ConclusionThis study suggests that short-term exposure to air pollutants is positively associated with an increase in numbers of asthma of people over 65 years of age in Sichuan province, and short-term exposure to excessive PM and NO2 brings health and economic burden to individuals and society.

Surgery combined with systemic chemotherapy is currently the main modality of cancer treatment. However, the development of cancer multidrug resistance and inevitable surgical residual lesions lead to high rates of cancer recurrence and mortality. Meanwhile, systemic drug toxic side effects and surgical bleeding complications seriously reduce the quality of life of patients. To avoid cancer multidrug resistance and comprehensively optimize cancer treatment, this work provides a novel injectable cell penetrating peptide octa-arginine (R8)-modified RADA16 (RR) self-assembling peptide nanofiber hydrogel as an anticancer drug carrier for multidrug-resistant cancer therapy. In RR hydrogel, highly compatible RADA16 functions as the β-sheet-based self-assembling backbone which tightly adheres to cancer tissue, prevents postoperative bleeding, and sustainedly releases anticancer drugs for long-term effects. The introduced R8 motifs endow RR hydrogel with the capacity to selectively kill cancer cells and reverse cancer multidrug resistance, which minimally impact normal tissue cells. Specifically, R8 motifs on the hydrogel scaffold selectively interfere with cancer cell membranes, increase drug uptake and penetration into cancer cells and tissues by enhancing multiple internalization pathways, and reduce drug efflux by inhibiting P-gp and BCRP multidrug-resistant transporters. Therefore, this study provides a multifunctional hydrogel material with strong potential for multidrug-resistant cancer clinical translation.

Our previous study found that large-leaf yellow tea (LYT) had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions (1/100 and 1/50, m/V) as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis (lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism (higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis (lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.

Abstract Background Liver failure is severe hepatic cellular damage caused by multiple factors that leads to clinical manifestations. Hepatic infiltration by malignancy is rarely reported as a cause of liver failure. Case presentation A 51-year-old male patient was admitted to the Wuhan Union Hospital complaining of bloating and jaundice. He had been diagnosed with polymyositis ten prior and was taking oral glucocorticoids. Physical examination revealed seroperitoneum and icteric sclera; laboratory tests revealed liver dysfunction, a coagulopathy, and negative results for the common causes of liver failure. Moreover, an ascitic tap and bone marrow aspirate and trephine confirmed a metastatic, poorly differentiated adenocarcinoma. These findings indicate that malignant infiltration is the most likely cause of liver failure. Regrettably, the patient refused complete liver and lymph node biopsies and was discharged on day 31. Conclusion Clinicians should consider the possibility of malignant infiltration when approaching a case of liver failure with prodromal symptoms or imaging abnormalities, especially in patients with autoimmune diseases, such as polymyositis.

Abstract Uncarialines A-E (1–5), five undescribed monoterpene indole alkaloids, together with five known analogues were obtained from the stems of Uncaria rhynchophylla. Alkaloids 1–3 were unique 3,4-seco-tricyclic alkaloids with a 6/5/10 ring system, while 4 and 5 possessed a rare rearranged scaffold originated from corynantheine-type alkaloids with C-2/C-7 oxidation. Their structures were characterized by a comprehensive analysis of MS, NMR, and ECD. Their effects on blood clotting times of human plasma were evaluated and alkaloid 5 had a slight prolongation effect on both thrombin time and activated partial thromboplastin time (p

Background: Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine during activities that increase abdominal pressure. In recent years, a considerable number of studies on SUI surgery have been published. However, there has been a lack of systematic quantification and comprehensive summarization of these studies. Bibliometrics is a discipline that utilizes measurement methods to quantify scientific literature. Thus, this study utilized publications from the Web of Science (WOS) as a data source and conducted a comprehensive analysis and visualization of studies related to SUI surgery in recent years using bibliometric techniques. Methods: We conducted a search and retrieved information on 988 studies related to SUI surgery in the WOS Core Collection. The data covered ten years from September 7, 2013, to September 7, 2023. We employed VOSviewer software, CiteSpace software, and Bibliometrix for analysis and visualization. Results: Over the ten years, the number of publications exhibited a fluctuating trend, initially decreasing and then increasing. The United States emerged as the leading contributor in terms of both publication volume and quality. The University of Alabama Birmingham ranked as the institution with the highest number of publications, while the International Urogynecology Journal featured the most publications among journals. Conclusions: This paper presents a bibliometric analysis of publications related to SUI surgery from 2013 to 2023. The aim is to offer researchers a concise overview of the field and inspire future research directions.

Cancer metabolism has emerged as a pivotal area of research recently. The ability to visualize and comprehend the metabolic processes of cancer holds immense clinical value, particularly in the diagnosis of malignant tumors and the assessment of treatment responses. Deuterium Metabolic Imaging (DMI), as a robust, simple, and versatile MR spectroscopic imaging tool, demonstrates promise in tumor diagnosis and treatment efficacy assessment. This review explored the latest developments and applications of DMI in oncology across various tumor metabolic axes, with a specific emphasis on its potential for clinical translation. DMI offers invaluable insights into tumor biology, treatment responses, and prognostic outcomes. Notably, DMI can identify early responses to immunotherapy, a prominent area of current research interest. In conclusion, DMI harbors the potential to evolve into a convenient and efficient imaging technique in clinical practice, thereby advancing precision medicine and improving the diagnosis and evaluation of cancer treatments.

Abstract Type 2 diabetes mellitus (T2DM), a complicated metabolic disease, might be developed or exacerbated by air pollution, resulting in economic and health burden to patients. So far, limited studies have estimated associations between short‐term exposure to air pollution and disease burden of T2DM in China. Hence, we aimed to estimate the associations and burden of ambient air pollutants (NO2, PM10, PM2.5, SO2, and CO) on hospital admissions (HAs) for T2DM using a time‐stratified case‐crossover design. Data on HAs for T2DM during 2017–2019 were collected from hospital electronic health records in nine cities in Sichuan Province using conditional poisson regression. Totally, 92,381 T2DM hospitalizations were recorded. There were significant short‐term effects of NO2, PM10, PM2.5, SO2 and CO on HAs for T2DM. A 10 μg/m3 increment of NO2, PM10, PM2.5, SO2 and CO as linked with a 3.39% (95% CI: 2.26%, 4.54%), 0.33% (95% CI: 0.04%, 0.62%), 0.76% (95% CI: 0.35%, 1.16%), 12.68% (95% CI: 8.14%, 17.42%) and 79.00% (95% CI: 39.81%, 129.18%) increase in HAs for T2DM at lag 6. Stratified analyses modified by age, sex, and season showed old (≥65 years) and female patients linked with higher impacts. Using WHO's air quality guidelines of NO2, PM10, PM2.5, and CO as the reference, the attributable number of T2DM HAs exceeding these pollutants exposures were 786, 323, 793, and 2,127 during 2017–2019. Besides, the total medical costs of 25.83, 10.54, 30.74, and 67.78 million China Yuan were attributed to NO2, PM10, PM2.5, and CO. In conclusion, short‐term exposures to air pollutants were associated with higher risks of HAs for T2DM.

Objectives This study aims to assess the relative of social support and psychological distress in disease activity among patients with Crohn’s disease (CD) in China, and explore whether sex moderates the relationship between disease activity and social support and psychological distress in CD.Design Our study has a cross-sectional design.Setting This was a single-centre study, which was conducted in Wuhan, China.Participants A total of 184 patients with CD at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were enrolled in this study; of these,162 patients were included in the final analysis.Primary and secondary outcome measures The main study outcome was the CD patients’ clinical and questionnaire data. The association of disease activity, social support and psychological distress with patients with CD was also evaluated based on the collected data.Results A total of 162 patients with CD were enrolled. Compared with patients with CD in remission (CD-R), the patients with CD in activity (CD-A) had higher C reactive protein (CRP) (p=0.001), anaemia (p

Abstract Background In response to an aging population, the Chinese government implemented the three-child policy in 2021 based on the comprehensive two-child policy. With the implementation of the new birth policy, people’s maternal and child health (MCH) needs will also increase. The allocation and fairness of MCH human resources directly affect people’s access to MCH services. The purpose of this study is to analyze the allocation of health human resources in Chinese maternal and child health care institutions, evaluate the fairness of the allocation, to provide a reference for the rational allocation of MCH human resources. Methods The data of health technicians, licensed (assistant) physicians, and registered nurses in maternal and child health care institutions nationwide from 2016 to 2020 were included. The health resource density index (HRDI) is used to evaluate the allocation level of MCH human resources. The Gini coefficient (G) and Theil index (T) are used to evaluate the fairness of the allocation of MCH human resources from the perspectives of population and geographic area. Results From 2016 to 2020, the average annual growth rate of the number of health technicians, licensed (assistant) physicians, and registered nurses in Chinese maternal and child health care institutions was 7.53, 6.88, and 9.12%, respectively. The Gini coefficient (G) of the three types of MCH human resources allocated by population were all below 0.23, and the Gini coefficient (G) allocated by geographical area were all above 0.65. The Theil index (T) of the three types of MCH human resources allocated by population was all lower than 0.06, and the Theil index (T) allocated by geographical area was all higher than 0.53. In addition, the three types of MCH human resources allocated by population and geographic area contributed more than 84% of the Theil index within the group (T intra ) to the Theil index (T). Conclusions China’s MCH human resources were fair in terms of population allocation, but unfair in terms of geographical area allocation. In the future, more attention should be paid to the geographical accessibility of MCH human resources, and the allocation of resources should comprehensively consider the two factors of serving the population and geographical area.

Natural adhesives have received a lot of attention recently. Here, the authors develop a natural biological adhesive from snail mucus that can adhere to wet tissue and be used to accelerate healing of skin wounds.

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia, resulting in serious cardiovascular diseases. Air pollution may cause heart rate disturbance, but there is no clear or consistent evidence that short-term exposure to air pollution leads to an increased risk of hospitalisation for symptomatic episodes of AF. This study aimed to assess the impact of short-term exposure to air pollution on inpatient numbers. Methods The inpatient records of AF cases in nine cities of the Sichuan Province, China and air pollution and meteorological data from 183 monitoring stations from 2017 to 2018 were collected. The impact of short-term exposure to air pollution on AF inpatients was evaluated using a time-stratified crossover case study design. The economic burden of AF attributable to air pollution was also estimated. Results A total of 5,958 patients with AF from 123 medical institutions were included in the analysis. Air pollutants had a significant impact on the number of patients with AF. The number increased by 2.5% (95% confidence interval [CI] = 1.006 to 1.044) and 1.8% (95% CI = 1.003–1.033) for every 10 µg/m3 increase in PM2.5, PM10, concentration, respectively. Moreover, the number increased by 12.7% (95% CI = 1.006 to 1.262) for every 10 µg/m3 increase of SO2 concentration. For every 0.1 μg/m3 increase in CO concentration, the number of inpatients with AF increased by 3.9% (95% CI = 1.010–1.070). People aged 65 years or older and women were more likely to be affected by air pollutants. The AF in 430 and 209 inpatients were attributable to PM2.5 and PM10, respectively. The total hospitalization expenses attributed to excessive exposure to PM2.5 and PM10 were 13.98 million CNY and 6.68 million CNY, respectively. Furthermore, the out-of-pocket expenses were 6.81 million CNY and 3.28 million CNY, respectively. Conclusions This study showed a strong correlation between air pollution and AF. Hence, there is a need to reduce air pollution to control health risks.

Abstract Although numerous studies have reported the association between sarcopenia and the prognosis of hepatocellular carcinoma (HCC) patients, there is lack of a newer and more comprehensive meta-analysis. Herein, a comprehensive literature search was performed on PubMed, Web of Science, the Cochrane Library, and Embase databases to identify relevant studies published up to February 2022. The outcomes were overall survival (OS), recurrence, progression‐free survival, tumor response, severe postoperative complications, and toxicity of drugs. A total of 57 studies involving 9790 HCC patients were included in the meta-analysis. The pooled prevalence of sarcopenia in HCC patients was 41.7% (95% CI 36.2–47.2%). Results demonstrated that sarcopenia was significantly associated with impaired OS (HR: 1.93, 95% CI 1.73–2.17, P

Abstract Background There are few studies on the effects of air pollutants on acute lower respiratory tract infections (ALRI) in children. Here, we investigated the relationship of fine particulate matter (PM2.5), inhalable particulate matter (PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2) with the daily number of hospitalizations for ALRI in children in Sichuan Province, China, and to estimate the economic burden of disease due to exposure to air pollutants. Methods We collected records of 192,079 cases of childhood ALRI hospitalization between January 1, 2017 and December 31, 2018 from nine municipal/prefecture medical institutions as well as the simultaneous meteorological and air pollution data from 183 monitoring sites in Sichuan Province. A time series-generalized additive model was used to analyze exposure responses and lagged effects while assessing the economic burden caused by air pollutant exposure after controlling for long-term trends, seasonality, day of the week, and meteorological factors. Results Our single-pollutant model shows that for each 10 μg/m3 increase in air pollutant concentration (1 μg/m3 for SO2), the effect estimates of PM2.5, PM10, SO2, and NO2 for pneumonia reached their maximum at lag4, lag010, lag010, and lag07, respectively, with relative risk (RR) values of 1.0064 (95% CI, 1.0004–1.0124), 1.0168(95% CI 1.0089–1.0248), 1.0278 (95% CI 1.0157–1.0400), and 1.0378 (95% CI, 1.0072–1.0692). By contrast, the effect estimates of PM2.5, PM10, SO2, and NO2 for bronchitis all reached their maximum at lag010, with RRs of 1.0133 (95% CI 1.0025–1.0242), 1.0161(95% CI 1.0085–1.0238), 1.0135 (95% CI 1.0025–1.0247), and 1.1133(95% CI 1.0739–1.1541). In addition, children aged 5–14 years were more vulnerable to air pollutants than those aged 0–4 years (p

Salt is a key ingredient that can both enhance the taste and extend the shelf life of fermented vegetables. However, it is important to note that excessive salt levels can have adverse effects on consumer health. This study aimed to investigate the impact of various salt additions (2%, 4%, 6%, 8%, and 10% wt/wt) on the flavor profile of fermented ciba pepper, a traditional Chinese fermented chili sauce, using gas chromatography–ion mobility spectrometry (GC-IMS) in combination with an electronic nose (E-nose). Fermented ciba pepper samples were prepared with different salt additions: 2% (LJA), 4% (LJB), 6% (LJC), 8% (LJD), and 10% (LJE) (wt/wt). The physicochemical and sensory properties of the fermented ciba pepper samples were evaluated. Sensory evaluation indicated that LJC and LJD received higher scores compared to the other groups. The total acid and amino acid nitrogen contents displayed contrasting trends with the salt additions (p < 0.05). The E-nose analysis successfully differentiated the flavor profiles of the ciba pepper samples fermented with varying salt additions. Additionally, the GC-IMS analysis identified a total of 72 volatile compounds, including 14 alcohols, 21 esters, nine aldehydes, four acids, eight ketones, three terpenes, and eight other substances. Notably, the ciba pepper samples with lower salt additions exhibited higher levels of alcohols, aldehydes, and esters. In conclusion, the addition of salt during the fermentation process significantly influenced the formation of flavor compounds in ciba pepper. This study provides valuable insights into ciba pepper fermentation with different salt additions and offers prospects for the development of low-salt fermented ciba pepper products.

Dual-energy CT has shown promising results in determining tumor characteristics and treatment effectiveness through spectral data by assessing normalized iodine concentration (nIC), normalized effective atomic number (nZeff), normalized electron density (nED), and extracellular volume (ECV). This study explores the value of quantitative parameters in contrast-enhanced dual-layer spectral detector CT (SDCT) as a potential tool for detecting lymph node activity in lymphoma patients. A retrospective analysis of 55 lymphoma patients with 289 lymph nodes, assessed through 18FDG-PET/CT and the Deauville five-point scale, revealed significantly higher values of nIC, nZeff, nED, and ECV in active lymph nodes compared to inactive ones (p < 0.001). Generalized linear mixed models showed statistically significant fixed-effect parameters for nIC, nZeff, and ECV (p < 0.05). The area under the receiver operating characteristic curve (AUROC) values of nIC, nZeff, and ECV reached 0.822, 0.845, and 0.811 for diagnosing lymph node activity. In conclusion, the use of g nIC, nZeff, and ECV as alternative imaging biomarkers to PET/CT for identifying lymph node activity in lymphoma holds potential as a reliable diagnostic tool that can guide treatment decisions.

Abstract Background Rare diseases impose a heavy economic burden on patients’ families and society worldwide. This study used the samples from Sichuan Province in China to estimate the curative care expenditure (CCE) of ten rare diseases, for supporting the prioritization of rare disease health policies. Methods Multi-stage cluster sampling method was adopted to investigate 9714 rare disease patients from 1556 medical institutions in Sichuan Province. Based on the System of Health Accounts 2011, this study estimated the total CCE of 10 rare diseases, financing schemes, and their allocation among different medical institutions and groups of people. Results In 2018, the total CCE of the ten rare diseases was $19.00 million, the three costliest rare diseases were Hemophilia ($4.38 million), Young-onset Parkinson’s disease ($2.96 million), and Systemic Sclerosis ($2.45 million). Household out-of-pocket expenditure (86.00% for outpatients, 41.60% for inpatients) and social health insurance (7.85% for outpatients; 39.58% for inpatients) were the main sources of financing CCE. The out-of-pocket expenditures for patients with Young-onset Parkinson’s disease, Congenital Scoliosis, and Autoimmune Encephalitis accounted for more than 60% of the total CCE. More than 80% of the rare disease CCE was incurred in general hospitals. The 40–59 age group accounted for the highest CCE (38.70%) while men spent slightly more (55.37%) than women (44.64%). Conclusions As rare disease treatment is costly and household out-of-pocket expenditure is high, we suggest taking steps to include rare disease drugs in the National Reimbursement Drug List and scientifically re-design insurance coverage. It is also necessary to explore a multi-tiered healthcare security system to pay for the CCE of rare diseases and reduce the economic burden on patients.

Objectives: This study aimed to evaluate the clinical value of metagenomic next-generation sequencing (mNGS) in patients with suspected lower respiratory tract infections. Methods: This retrospective study reviewed patients with suspected lower respiratory tract infections at the Wuhan Union Hospital. Data including demographic, laboratory, and radiological profiles; treatment; and outcomes were recorded and analyzed. Results: mNGS identified pathogenic microbes in 100/140 (71.4%) patients, although 135 (96.4%) had received empiric antibiotic treatment before the mNGS tests. Single bacterial infection (35/100, 35%) was the most common type of infection in patients with positive mNGS results, followed by single fungal infection (14/100, 14%), bacterial-viral coinfection (14/100, 14%), single viral infection (12/100, 12%), bacterial-fungal coinfection (9/100, 9%), fungal-viral coinfection (9/100, 9%), and bacterial-fungal-viral coinfection (7/100, 7%). Moreover, compared with culture test, mNGS showed higher sensitivity (63/85, 74.1% vs 22/85, 25.9% P = 0.001) and lower processing time (24 hours vs 48 hours). Antibiotic treatment was adjusted or confirmed based on the mNGS results in 123 (87.9%) patients, including five (3.6%), 33 (23.6%), and 85 (60.7%) patients, in whom treatment was downgraded, upgraded, and unchanged, respectively. Almost all patients, regardless of escalation, de-escalation, or no change in treatment, showed significant improvement in clinical symptoms and inflammatory indicators. In addition, 17 (12.1%) patients were referred to Wuhan Pulmonary Hospital for further treatment because of confirmed or suspected tuberculosis. Conclusion: mNGS could be a promising technique for microbiological diagnosis and antibiotic management, potentially improving outcomes for patients.

Two endophytic fungi Trichoderma afroharzianum (HP-3) and Alternaria alstroemeriae (HP-7) were isolated and purified from the fresh root of Dryopteris crassirhizoma. Chemical investigation of the two fungi resulted in the isolation of two new phenols 2,4-dihydroxy-3-farnesyl-5-methoxy benzoic acid (1) and 2-hydroxyphenethyl 2-phenylacetate (2), together with 22 known compounds. Their structures were elucidated by NMR, UV, IR, HRESIMS, and comparison to the literature data. Compounds 15 and 16 showed significant antibacterial activity against Micrococcus lysodeikticus with MIC value of 6.25 μg/mL, while 8 and 14 displayed moderate inhibitory activities against several plant pathogenic fungi and clinically important bacterial strains. This is the first study to report the isolation, identification, and antimicrobial properties of metabolites from endophytic fungi of D. crassirhizoma. Our findings may provide lead compounds for the development of new antibacterial agents.

Panzao (Ziziphus jujuba Mill. cv. ‘Jingcang1’) have a short shelf-life, which hampers their marketability. To investigate effects of combined pre- and postharvest treatments on quality and softening during storage, preharvest Guomantian foliar fertilizer (FF) spray and postharvest salicylic acid (SA) dip were applied to panzao. By day 63 of storage, fruit firmness responded to treatment in the order of FF+SA treatment > FF or SA treatments > Control. All treatments inhibited fruit reddening during storage and, compared with those of the control, alleviated the decline in total soluble solids, ascorbic acid, and phenol contents and decreased the oxidative aging process, which was consistent with the change in firmness. The FF+SA treatment reduced the activities of amylase, cellulase, polygalacturonase, and β-glucosidase, which decreased the degradation of macromolecules including starch, cellulose, and pectin. Principal component analysis showed that FF+SA exhibited a synergistic effect and was the most effective treatment for maintaining fruit quality during storage. FF increased accumulation of nutrients during growth and improved quality, while SA delayed the decline in fruit quality and reduced softening. These results provide the theoretical basis and technical knowledge for improving the shelf-life of panzao during storage and long-distance transportation.

This study aims to propose and evaluate DR-CycleGAN, a disentangled unsupervised network by introducing a novel content-consistency loss, for removing arterial-phase motion artifacts in gadoxetic acid-enhanced liver MRI examinations. From June 2020 to July 2021, gadoxetic acid-enhanced liver MRI data were retrospectively collected in this center to establish training and testing datasets. Motion artifacts were semi-quantitatively assessed using a five-point Likert scale (1 = no artifact, 2 = mild, 3 = moderate, 4 = severe, and 5 = non-diagnostic) and quantitatively evaluated using the structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR). The datasets comprised a training dataset (308 examinations, including 58 examinations with artifact grade = 1 and 250 examinations with artifact grade ≥ 2), a paired test dataset (320 examinations, including 160 examinations with artifact grade = 1 and paired 160 examinations with simulated motion artifacts of grade ≥ 2), and an unpaired test dataset (474 examinations with artifact grade ranging from 1 to 5). The performance of DR-CycleGAN was evaluated and compared with a state-of-the-art network, Cycle-MedGAN V2.0. As a result, in the paired test dataset, DR-CycleGAN demonstrated significantly higher SSIM and PSNR values and lower motion artifact grades compared to Cycle-MedGAN V2.0 (0.89 ± 0.07 vs. 0.84 ± 0.09, 32.88 ± 2.11 vs. 30.81 ± 2.64, and 2.7 ± 0.7 vs. 3.0 ± 0.9, respectively; p < 0.001 each). In the unpaired test dataset, DR-CycleGAN also exhibited a superior motion artifact correction performance, resulting in a significant decrease in motion artifact grades from 2.9 ± 1.3 to 2.0 ± 0.6 compared to Cycle-MedGAN V2.0 (to 2.4 ± 0.9, p < 0.001). In conclusion, DR-CycleGAN effectively reduces motion artifacts in the arterial phase images of gadoxetic acid-enhanced liver MRI examinations, offering the potential to enhance image quality.

Introduction: Lung cancer, one of the most frequent malignancies, has a high death rate and an increased number of new cases globally. Ginkgo biloba has been used for many years in the treatment of lung cancer. Ginkgetin is the key active ingredient extracted from Ginkgo biloba. However, the mechanism by which ginkgetin inhibits the invasive metastasis of lung cancer is unclear.Methods: We used a network pharmacology approach to obtain the molecular mechanism by which ginkgetin inhibits lung cancer metastasis. Then we analyzed potential target proteins between ginkgetin and lung cancer. Finally, we validated with molecular docking and experimental validation.Results: By analyzing the intersecting genes of lung cancer and ginkgetin, there were 79 intersecting genes, which were mainly involved in the positive regulation of cell migration, with the cancer pathway being one of the most enriched pathways. The results of in vitro experiments showed that GK had a large inhibitory effect on cell invasion and metastasis of A549 and H1299. In vivo animals GK had a great inhibitory effect on metastasis of LLC.Conclusion: This study identified the potential related GK molecular targets and signaling pathways in treating human lung cancer using network pharmacological approaches. Experiments confirmed that GK inhibits the Akt/GSK-3β/Snail and Wnt/β-catenin cascade initiation in A549, H1299 and LLC cells, preventing metastasis. This study’s results align with the hypotheses derived from the network pharmacology analysis.

BackgroundEctopic pregnancy (EP) is one of the leading causes of death in women in early pregnancy, and the mortality of EP have gradually decreased over time in developed countries such as the United Kingdom and the United States. However, epidemiological information on EP has been lacking in recent years, so we analyzed EP data over a thirty-year period from 1990-2019 with the help of Global Burden of Disease study (GBD) data to fill this gap.MethodsAccording to the EP data in GBD for the three decades from 1990 to 2019, we used estimated annual percentage changes (EAPC) to assess the trend of age-standardized incidence rate (ASIR), age-standardized death rate (ASDR) and age-standardized disability adjusted life years (AS-DALYs) trends in EP and to explore the correlation between socio-demographic index (SDI) stratification, age stratification and EP.ResultsGlobal ASIR, ASDR, AS-DALYs for EP in 2019 are 170.33/100,000 persons (95% UI: 133.18 to 218.49), 0.16/100,000 persons (95% UI, 0.14 to 0.19) and 9.69/100,000 persons (95% UI, 8.27 to 11.31), respectively. At the overall level, ASDR is significantly negatively correlated with SDI values (R = -0.699, p < 0.001). Besides that, ASDR and AS-DALYs have basically the same pattern. In addition, iron deficiency is one of the risk factors for EP.ConclusionsIn the past three decades, the morbidity, mortality and disease burden of EP have gradually decreased. It is noteworthy that some economically disadvantaged areas are still experiencing an increase in all indicators, therefore, it is more important to strengthen the protection of women from ethnic minorities and low-income groups.

Abstract Background Coronary heart disease (CHD), the leading cause of death globally, might be developed or exacerbated by air pollution, resulting high burden to patients. To date, limited studies have estimated the relations between short-term exposure to air pollution and CHD disease burden in China, with inconsistent results. Hence, we aimed to estimate the short-term impact and burden of ambient PM pollutants on hospitalizations of CHD and specific CHD. Methods PM10 and PM2.5 were measured at 82 monitoring stations in 9 cities in Sichuan Province, China during 2017-2018. Based on the time-stratified case-crossover design, the effects of short-term exposure to particle matter (PM) pollution on coronary heart disease (CHD) hospital admissions were estimated. Meanwhile, the linked burden of CHD owing to ambient PM pollution were estimated. Results A total of 104,779 CHD records were derived from 153 hospitals from these 9 cities. There were significant effects of PM pollution on hospital admissions (HAs) for CHD and specific CHD in Sichuan Province. A 10 μg/m3 increase of PM10 and PM2.5 was linked with a 0.46% (95% CI: 0.08, 0.84%), and 0.57% (95% CI: 0.05, 1.09%) increments in HAs for CHD at lag7, respectively. The health effects of air pollutants were comparable modified by age, season and gender, showing old (≥ 65 years) and in cold season being more vulnerable to the effects of ambient air pollution, while gender-specific effects is positive but not conclusive. Involving the WHO’s air quality guidelines as the reference, 1784 and 2847 total cases of HAs for CHD could be attributable to PM10 and PM2.5, separately. The total medical cost that could be attributable to exceeding PM10 and PM2.5 were 42.04 and 67.25 million CNY from 2017 to 2018, respectively. Conclusions This study suggested that the short-term exposure to air pollutants were associated with increased HAs for CHD in Sichuan Province, which could be implications for local environment improvement and policy reference.

Abstract Purpose To evaluate the clinical effects of concentrated growth factors (CGFs) combined with bone substitutes for alveolar ridge preservation (ARP) in the maxillary molar area. Methods Thirty-six patients who underwent extraction of the upper molars were recruited and randomly divided into three groups: 1. Grafted with CGFs combined with deproteinized bovine bone mineral (DBBM) and covered with CGFs membrane (CGFs/DBBM group), 2. Grafted with DBBM alone and covered with collagen membrane (DBBM group), 3. Control group spontaneous healing. The area of the alveolar bone in center (C-), mesial (M-) and distal (D-) section was compared with preoperative in radiography. Bone cores were obtained for histopathology observation and comparison. Results In C-, M- and D-section, the alveolar ridge area in all three groups was significantly reduced at 8 months postoperatively compared to the baseline (P

Fucosylated glycosaminoglycan (FG) from sea cucumbers has been reported to have anticoagulant effects via targeting intrinsic tenase. However, FG from natural source also potentially poses risks due to its FXIIa activation and platelet aggregating effects. Here, we found that the effect of FG on human platelet aggregation depended on both the sulfation pattern and chain length. FGs with higher content of Fuc2S4S and larger molecular weight (≥14 kD) had stronger activity. Both platelet aggregation and P-selectin expression induced by TaFG (an FG from Thelenota ananas) were decreased as the molecular weight reduced. Ticagrelor, aspirin and wortmannin completely blocked the secretion (ADP) but only partially blocked the aggregation induced by TaFG. Tirofiban an αIIbβ3 antagonist however potently inhibited both the secretion and aggregation, with IC50 of 6.01 ± 1.1.97 nM. Furthermore, TaFG could bind to human αIIbβ3 with high affinity, and the affinities of two FGs were paralleled with their activity in platelet aggregation or activation. These results indicated that αIIbβ3 played an important role in TaFG-induced platelet aggregation which was mediated by PI3K, and that platelet secretion was required for the amplification of aggregation.