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Abstract Objective The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the isolation of tumor cells, lymphocytes, and dendritic cells (DCs) derived from ovarian cancer tissues or ascites. Subsequently, the focus lies on the generation of dendritic cell-tumor infiltrating lymphocytes (DC-TILs) exhibiting specific cytotoxic capabilities aimed at targeted therapeutic interventions. The cytotoxic impact of DC-TIL interactions on tumor cells was investigated through in vitro experimentation. This research aims to provide fundamental experimental insights for the future clinical advancement of TIL therapy in ovarian cancer. Methods The experimental samples included fresh surgical specimens and ascites specimens procured from three patients (ranging in age from 32 to 75), sourced from the Department of Gynecology at the Third Bethune Hospital of Jilin University. TILs were extracted through in vitro isolation from solid tumor tissues, while primary tumor cells and DCs were obtained from ascites specimens. Tumor-specific antigens derived from patient tumor cells were utilized to stimulate the maturation of DCs. TILs were subsequently co-cultured with antigen-stimulated DC cells. Subsequently, TILs with specific killing effects were obtained, and the cytotoxic impact of DC-TILs on tumor cells was detected in vitro. Results (1) TILs were successfully obtained through expansion from the tumor tissue of a patient diagnosed with ovarian cancer. (2) DCs were successfully induced from ascites cells harvested from patients diagnosed with ovarian cancer. (3) TILs significantly enhanced the cytotoxicity of tumor cells following DC stimulation. Conclusion TILs have the capacity to augment the cytotoxicity directed towards tumor cells following DC stimulation.

Abstract Background The widespread acceptance of early surgery as a treatment for acute intertrochanteric fracture (ITF) has been accompanied by ongoing controversy due to conflicting conclusions presented in previous studies. This study aims to compare the occurrence of perioperative complications and mortality, as well as functional outcomes in older patients with ITF who underwent either early or delayed surgery. Methods A retrospective multicenter cohort study involving 7414 patients with ITF between Jan. 2017 and Dec. 2021 was conducted. After predefined participants selection inclusion and exclusion criteria, 2323 surgically treated ITF patients were included and analyzed utilizing propensity score matching (PSM) method. Their demographics, injury-related data, surgery-related data, and perioperative adverse outcomes during hospitalization were collected and compared between the early or delayed surgery groups by PSM with a 1:4 ratio. All participants received a minimum of two-year follow-up and perioperative outcomes, functional outcomes, and survival analyses were conducted and compared. Results After adjustment for potential confounders, there were no significant difference in surgery duration, intraoperative blood loss, transfusion rate, mortality rates, functional outcomes, and perioperative complications rates including severe complications, cardiac complications, pulmonary complications, and neurological complications regardless of whether the patient was treated with early or delayed surgery (all P > 0.05). Although length of hospital stay (mean, 11.5 versus 14.4 days, P

Abstract Background To analyze the association between the hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD). Methods HGI represented the difference between laboratory measured Hemoglobin A1c (HbA1c) and predicted HbA1c based on a liner regression between Hb1Ac and fasting plasma glucose (FPG). A total of 10 598 patients who treated with percutaneous coronary intervention (PCI) were stratified into three groups (low HGI group: HGI

Abstract Background Evidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study. Methods A large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups. Results A total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a “U -shape” relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (

Abstract Purpose The atherogenic index of plasma (AIP) is a novel comprehensive lipid index. We aimed to investigate a possible relationship between AIP index and kidney stones in US adults. Methods This cross-sectional study was conducted among adults with complete AIP index and questionnaire records on kidney stones from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. The AIP index served as the exposure variable, defined as the logarithm of the ratio between triglycerides (TG, mmol/L) and high-density lipoprotein cholesterol (HDL-c, mmol/L). Self-reported history of kidney stones was utilized as the outcome variable. The independent relationship between AIP index and the risk of kidney stones was fully assessed. Results A total of 14,833 participants were included in this study, with an average AIP index of -0.07 ± 0.01. The proportion of kidney stones progressively increased with higher AIP index tertile intervals (7.33% vs. 9.97% vs. 12.57%, P 0.05). Conclusions The AIP index may be a potential epidemiological tool to quantify the role of dyslipidemia in the risk of kidney stones in US adults.

Membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease in which PLA2R1 is the main autoantibody. It has become the most common cause of adult nephrotic syndrome, and about one-third of patients can progress to end-stage kidney disease, but its pathogenesis is still unclear. Animal models can be used as suitable tools to study the pathogenesis and treatment of MN. The previous Heymann nephritis rat model and C-BSA animal model are widely used to study the pathogenesis of MN. However, the lack of target antigen expression in podocytes of model animals (especially rodents) restricts the application. In recent years, researchers constructed animal models of antigen-specific MN, such as THSD7A, PLA2R1, which more truly simulate the pathogenesis and pathological features of MN and provide more choices for the follow-up researchers. When selecting these MN models, we need to consider many aspects, including cost, difficulty of model preparation, labor force, and whether the final model can answer the research questions. This review is to comprehensively evaluate the mechanism, advantages and disadvantages and feasibility of existing animal models, and provide new reference for the pathogenesis and treatment of MN.

PurposeThe Cardiometabolic Index (CMI) is a novel marker of visceral obesity and dyslipidemia. Our study aimed to explore the association between CMI and kidney stones among US adults.MethodsThis cross-sectional study was conducted among adults with complete records of CMI and kidney stones information from the 2011 to 2018 National Health and Nutrition Examination Survey (NHANES). Inverse probability treatment weighting (IPTW) was used to balance the baseline characteristics of the study population. The independent relationship between CMI and kidney stones was evaluated using IPTW-adjusted multivariate logistic regression, restricted cubic splines (RCS), and subgroup analysis.ResultsA total of 9,177 participants, with an average CMI of 0.72 (0.99), were included in this study. The IPTW-adjusted logistic regression revealed that CMI was an independent risk factor for kidney stones. The adjusted odds ratio (OR) for kidney stones were 1.39 (95% CI: 1.24 – 1.56, P < 0.001) for the second CMI tertile and 1.31 (95% CI: 1.17 – 1.47, P < 0.001) for the third CMI tertile, compared with the first CMI tertile. A linear relationship between CMI levels and kidney stone risk was observed in the RCS analysis. Subgroup analysis showed that the association between CMI levels and kidney stone risk remained stable across groups.ConclusionsA positive association between CMI level and the risk of kidney stones was observed among US adults in our study. Further large-scale prospective studies are needed to validate our findings.

Abstract Historic districts are integral components of urban space, possessing diverse ecosystems that can offer various cultural services to the public. Urbanization and tourism development have led to the degradation of the ecological landscapes within historic districts, impacting sustainable development. Incorporating Cultural Ecosystem Services (CES) into the environmental research of historic districts can meet people's spiritual needs, enhance intangible benefits for humanity, and promote the conservation of the ecological environment within historic districts. Therefore, this study conducted perceptual quantification research on CES in four typical historic districts in Fuzhou City, crawling the online comment data through Python, mined its potential themes using Biterm Topic Model (BTM), and extracted and categorized the indicators of CES of historic districts by combining with expert consultation; meanwhile, the satisfaction of CES of historic districts is further explored with the help of two methods, namely, sentiment analysis and Importance-Performance analysis (IPA), and summarized the public perception of CES of historic districts. The results of the study show that: (1) the dimensions of public perception of CES in urban historic districts include Cultural Heritage, Leisure Tourism, Aesthetic Enjoyment, Spiritual Fulfillment, Inspiration, and Science Education six indicators, of which Leisure Tourism is most easily perceived by the public, but its satisfaction is not high; (2) the public's perception of positive emotions towards the CES of historic districts in Fuzhou is greater than negative emotions, with positive emotions accounting for 80.61%; (3) the public's overall satisfaction with the CES of Fuzhou's historic districts is high, and according to the final analysis results of the IPA, the four historic districts of Fuzhou are respectively proposed to improve the opinions. Based on big data, this study explores the public perception characteristics of CES in Fuzhou historic districts to promote its sustainable development and improve public well-being, which is of great significance to protecting the ecological environment of historic districts and improving the quality of cultural services.

Abstract Background The real-world tuberculosis (TB) surveillance data was generally incomplete due to underreporting and underdiagnosis. The inventory study aimed to assess and quantify the incompletion of surveillance systems in southwestern China. Methods The inventory study was conducted at randomly selected health facilities (HF) by multi-stage stratified cluster sampling. The participants were included in the period between August of 2020 in province-level and prefecture-level HF, and in the period between June to December of 2020 in other categories of HF respectively. The clinical committee confirmed medical records were matched to the National Notifiable Disease Reporting System (NNDRS) and the Tuberculosis Information Management System (TBIMS) to define the report and register status. The underreporting and under-register rates were evaluated based on the matched data, and factors associated with underreport and under-register were assessed by the 2-level logistic multilevel model (MLM). Results We enrolled 7,749 confirmed TB cases in the analysis. The province representative overall underreport rate to NNDRS was 1.6% (95% confidence interval, 95% CI, 1.3 − 1.9), and the overall under-register rate to TBIMS was 9.6% (95% CI, 8.9–10.3). The various underreport and under-register rates were displayed in different stratifications of background TB disease burden, HF level, HF category, and data source of the medical record in HF among prefectures of the province. The intraclass correlation coefficient (ICC) was 0.57 for the underreporting null MLM, indicating the facility-level cluster effect contributes a great share of variation in total variance. The two-level logistic MLM showed the data source of medical records in HF, diagnostic category of TB, and type of TB were associated with underreporting by adjusting other factors (p

The morphological characteristics, ecological habits, and physiological structures of fish vary rapidly in the early growth and development stage. Understanding the changes in the postembryonic early development morphology of organs or tissues could provide basic information for the classification or identification of fish and the investigation or utilization of early resources. Morphological characteristic observation is one of the most commonly used methods. The existing studies on the early development of a certain trait in the late larval and juvenile stage are unclear. Most of the digital images are side views, resulting in a lack of dorsal views, ventral views, or local images, which is not conducive to the understanding of larval and juvenile. In this study, the variations in observable, measurable, and countable traits in postembryonic early development of Thamnaconus septentrionalis were explored using optical microscopy and stereomicroscopy. The observable traits included the developmental changes of yolk sac, scales, and notochord curvature. The measurable traits included the growth changes of total length, body length, body height, and oral fissure. The countable characters included the number of fins in the second dorsal fin, anal fin, caudal fin, and the number of pterygiophore. The results showed that at (23.0±1.0) ℃, the newly hatched larvae moved up and down in the water, with a phenomenon of convergent clustering under light irradiation; the pectoral fin appeared at 1 d, and the heart rate was approximately 50 beats/min; the optic capsule was completely black, the maxillar appeared, the oral fissure extended below the eyes, the yolk sac disappeared, and the first dorsal fin base appeared at 4 d; the girdle was single and colorless and began from the front edge of the belly, the oil globule disappeared, and the pelvic fin base appeared at 7 d; the first dorsal fin base and pelvic fin base broke membrane at 8 d; the first dorsal fin and pelvic fin were significantly longer than before, transparent rounded scales were observed at 9 d; swimming ability was improved, indicated by hovering back and forth gnawing pool wall, transversally conical barbs appeared at the base of the first dorsal fin at 11 d; the swim bladder and postcleithrum on both sides of the belly were clearly visible at 12 d; the second dorsal fin and anal fin pterygiophore appeared at 14 d, the second dorsal fin pterygiophore spans seven sarcomeres and the anal fin pterygiophore spans six sarcomeres. There are 10~12 melanin masses in the second dorsal fin and 5~6 in the anal fin, the conical teeth appeared on the upper and lower jaws at 16 d; the second dorsal fin and anal fin were differentiated at 19 d; the swim bladder fills about 25% of the abdominal cavity; notochord curves upward clearly and the stalk of caudal fin came out at 20 d; the fin strips of the second dorsal fin, anal fin, and caudal fin were well-developed at 24 d; the open mouth was round and changed from swallowing to sucking at 30 d, and the rainbow cells were colorful and the body surface near the gill was the most dense; the abdominal cavity has a strong metallic texture, the hard spine of the pelvic fin was degraded, close to the girdle at 39 d; 4~5 black bands were arranged regularly on the body, and the lateral line was consistent with the vertebral column at 50 d. The R2 values of the curve equations of measurable traits were all greater than 0.90. The height of the first dorsal fin increased exponentially 4~30 d. The visual sac increased linearly from 0~11 d to 11~20 d, and the increment of 0~11 d was less than that of 11~20 d, while the increment of 21~30 d was exponential. The oral fissure in 4~13 d and 22~30 d increased linearly, while that in 13~22 d decreased linearly. The total length, body length, and body height increased linearly before the inflection point and exponentially after the inflection point, which was concentrated in 19~23 d. The number of fin pterygiophore of the second dorsal fin was 31~36, while that in the anal fin was 33~35. The number of pectoral fins and caudal fins were 15~18 and 12, respectively. In conclusion, metamorphosis occurs in the postembryonic early development of T. septentrionalis, showing an allometric growth pattern, with a slow linear growth in the rotifer-feeding stage and a fast exponential growth in the artemia-feeding stage. The changes in the first dorsal fin and pelvic fin were correlated with age in days. The changes in the second dorsal and anal fins were correlated with the total length. This study enriches the early biological theory of T. septentrionalis and provides basic data for the investigation or utilization of its seedling breeding and resources. The partial enlarged detail is helpful for scholars to further understand the larval or juvenile fish and perform deep research.

Objective The incidence of acute kidney injury (AKI) in pediatric patients has been increasing over the years, and AKI significantly impacts children’s health and quality of life. This article reviews the current epidemiological research on pediatric AKI.Methods The clinical data of hospitalized children aged 0 to 14 years from 20 different hospitals in Hunan Province, China, collected from December 2017 to February 2018, were analyzed. The incidence rate, misdiagnosis rate, main causes, and medical costs of AKI in hospitalized children were examined.Results A total of 29,639 patients were included, with an AKI incidence rate of 4.34% (1286/29,639). Among the 1286 AKI patients, 863 (67.11%) were classified as AKI stage 1324 (25.19%) as AKI stage 2, and 99 (7.7%) as AKI stage 3. AKI patients had significantly longer hospital stays [6.0 (4.0, 10) days vs. 6.0 (4.0, 8.0) days, p

Background The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN.Methods 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman’s correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission.Results In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766.Conclusions FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

Due to the discovery of Crassostrea dianbaiensis and C. iredalei in southern China, they may be considered important germplasm resources. However, the artificial breeding and large-scale aquaculture of these two oysters have not been extensively developed in China. Therefore, this study evaluated the artificial breeding and aquaculture potential of these two oysters and compared them with an economic species, C. hongkongensis in southern China. In addition, this study also investigated the effects of different species, sites, and their interactions on growth traits. The results indicated that under different salinities (16–32 ppt), the D larval rate of C. dianbaiensis and C. iredalei were both high, C. dianbaiensis could reach over 60 % (20–32 ppt), while C. iredalei could reach over 85 % (16–28 ppt). At the 15th day, the survival rates of C. dianbaiensis and C. iredalei larvae were significantly higher than those of C. hongkongensis (P < 0.05), but there was no significant difference between these two oysters. In terms of the growth traits, the shell height of C. iredalei larvae was significantly higher than that of C. dianbaiensis and C. hongkongensis (P < 0.05), and the growth tendency was different from the larvae (C. dianbaiensis > C. hongkongensis > C. iredalei). During the grow-out stage (90th to 360th days), the cumulative survival rate was significantly influenced by sites and interaction effects (P < 0.05). On the 360th day, at the Sanbaimen site, the cumulative survival rate of C. dianbaiensis was significantly higher than that of C. iredalei and C. hongkongensis (P < 0.05). For yearling progeny, at the Sanbaimen site, the shell height of C. dianbaiensis was significantly higher than that of C. iredalei and C. hongkongensis, influenced by different species, site, and interaction effects (P < 0.001). In terms of relative yield, at the Sanbaimen site, the relative yield of C. dianbaiensis was significantly higher than that of C. hongkongensis (P < 0.05), while there was no significant difference between C. iredalei and C. hongkongensis. In conclusion, our study demonstrates that the potential for large-scale commercial aquaculture of C. dianbaiensis is feasible and has an improvement effect on the existing commercial oyster industry in southern China.

Sepsis-induced acute lung injury (ALI) is a major cause of death among patients with sepsis in intensive care units. By analyzing a model of sepsis-induced ALI using lipopolysaccharide (LPS) and cecal ligation and puncture (CLP), treatment methods and strategies to protect against ALI were discussed, which could provide an experimental basis for the clinical treatment of sepsis-induced ALI. Recent studies have found that an imbalance in autophagy, ferroptosis, and pyroptosis is a key mechanism that triggers sepsis-induced ALI, and regulating these death mechanisms can improve lung injuries caused by LPS or CLP. This article summarized and reviewed the mechanisms and regulatory networks of autophagy, ferroptosis, and pyroptosis and their important roles in the process of LPS/CLP-induced ALI in sepsis, discusses the possible targeted drugs of the above mechanisms and their effects, describes their dilemma and prospects, and provides new perspectives for the future treatment of sepsis-induced ALI.

In the current study, a novel crude polysaccharide (cNCEP) was extracted from N. commune Vaucher utilizing ultrasonic-assisted extraction (UAE) with 60 % ethanol, employing response surface methodology. The optimal yield of cNCEP was determined to be 8.07 ± 0.08 mg/g, achieved through ultrasonic-assisted extraction under the conditions of a material-to-liquid ratio of 1:22, temperature of 56 °C, power of 570 W, and duration of 147 min. Subsequent purification of NCEP via Sephadex G75 resulted in a novel polysaccharide with a molecular weight of 20.466 kDa. NCEP exhibited significant scavenging activites against DPPH and hydroxyl radicals, as well as notable in vitro immunomodulatory properties. Furthermore, the mechanisms underlying the immunomodulatory effects of NCEP, involving enhancement of immunity, were investigated, revealing potential regulation of MAPK and TLR4-IRF7-NF-κB signaling pathways through RNA-Seq and Western blot analyses. These findings highlight the promising potential of NCEP as an organic immunomodulatory agent and functional food ingredient.

Objectives Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD).Design The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study.Setting The study setting was Xinjiang Medical University Affiliated First Hospital in China.Participants Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia's development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.

Abstract Background Type 2 diabetes mellitus (T2DM) is a common metabolic disease that requires long-term management and treatment. Digital intervention, as an emerging medical model, has been widely used in the treatment of T2DM patients. Behavioral economics theory provides a favorable perspective for studying the effect of digital intervention because it can reveal the decision-making mechanisms behind human behavior and provide more effective interventions for digital intervention. The purpose of this trial is to evaluate the impact of behaviorally based digital intervention on T2DM patients’ HbA1c, self-monitoring of blood glucose (SMBG) testing rate, diabetes self-efficacy, and other indicators compared to conventional treatment. Methods This trial is a prospective randomized controlled trial conducted at the First People’s Hospital of Kunshan City from April 1, 2023, to December 31, 2024, with a follow-up period of 3 months. The specific randomization method was established and implemented through the EDC clinical trial center’s randomization system. We will measure and collect baseline data from three groups, including Group A: digital intervention + virtual incentives + conventional treatment, Group B: digital intervention + physical incentives + conventional treatment, and Group C: conventional treatment. HbA1c, weight, SMBG testing rate, diabetes self-efficacy, and diabetes-related medical expenses will be recorded at baseline, 1 month, 2 months, and 3 months for all three groups. The Shapiro-Wilk test will be used to test for normality, and Pearson correlation analysis will be used for correlation analysis. Dropouts will be analyzed separately. Analysis of variance or exact probability calculation will be used to compare demographic data and other baseline indicators. Discussion This study is a novel clinical trial that integrates multiple disciplines (economics and medicine) and uses digital technology to deliver the intervention. Most published studies were offline interventions based on behavioral economics theory, but very few were on online interventions for T2DM patients. This study has both novelty and social value. Trial registration Chinese Clinical Trial Registry ChiCTR2300070753. Registered on 2023/04/22.

Biochar, plants, and earthworms have good remediation effects on cadmium (Cd)-contaminated soils. However, few studies have combined all three technologies to explore the treatment of Cd-contaminated soils. This study investigated the effect of corn straw biochar addition (1% and 5% mass ratios) on soil Cd treatment in an Eisenia fetida–Solanum nigrum system. The addition of corn straw biochar increased soil pH, total nitrogen (TN), total phosphorus (TP), and soil organic carbon (SOC); adding 5% (w/w) biochar under Cd stress resulted in significant increases (P

Abstract Poverty eradication is the first goal on the United Nations’ list of 17 Sustainable Development Goals (SDGs). However, the relationships between poverty eradication and the other SDGs remain unclear, and thus current knowledge is insufficient to support the synergized achievement of the SDGs. China eliminated extreme poverty in 2021, and thus in this study, we analyzed the variations in sustainability and equality related to the environment and the provision of public services in China during the poverty eradication program from 2010 to 2020. We combined statistical data, point of interest data, and environmental monitoring and remote sensing data to evaluate progress in China’s 832 poverty-stricken counties. The results showed that the mean values of environmental and public service sustainability indicators improved from 2010 to 2020. In addition, the mean Theil index value decreased from 0.46 to 0.35 during this period, implying a reduction in inequality. Inequality between poverty-stricken and non-poverty-stricken areas accounted for 9.3% of overall inequality among the counties in 2010, and this had decreased to 7.7% in 2020. However, unbalanced regional investment resulted in increased gaps between poverty-stricken and non-poverty-stricken counties in relation to education and health care. Overall, 15% of the population and 54.8% of the land area in poverty-stricken counties experienced both a loss of their advantage in terms of environmental quality compared with non-poverty-stricken counties and greater lags in the provision of public services. Linear estimation showed that investment in poverty-stricken counties should be increased by 226.2 and 72.0% in relation to education and health care, respectively, to eliminate these inequalities.

Enhanced dewatering remains a major challenge in sludge disposal. In this paper, a thermal solidification treatment under low temperatures was first and successfully employed to improve the dewaterability of sludge from water-based ink wastewater. A total of 95.1% of dewatering ratio, 36.6% of moisture content, and 91.9% of sludge volume reduction could be acquired at 75 °C and 30 min setting time by the reported approach. The DSC results indicated that a large amount of bound water trapped in sludge could be released into the bulk solution to become free water after thermal solidification treatment. The bound water content of sludge can be reduced from 3.40 to 0.20 g g−1 dry solid. The reported thermal solidification treatment is a thermophysical process that does not involve the solubilization of solid substrates and does not cause an increase in the COD value of dehydrated water. The obtained sludge after cooling was a clot of compacted cake with a uniform coralline-like structure. The softening and shrinking of acrylic resin within the sludge during heating contributed to the formation of compacted cake and thus enhanced the dewaterability. This study offers an economical and efficient treatment of sludge for the water-based ink printing industry.

Abstract BackgroundPredicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes. ObjectiveThe aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes. MethodsWe assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose

ObjectiveTo report the trend changes of the prevalence, incidence, and disability-adjusted life years (DALYs) of knee osteoarthritis (KOA) according to age, sex, sociodemographic index (SDI), and income.MethodsThis analysis used estimates from the broader Global Burden of Disease (GBD) study 2019, which covered 201 countries from 1990 to 2019. National prevalence, incidence, and DALYs were shown by using ggplot2 and maps packages. Five-year intervals were used for age groupings. The Commonwealth and the World Bank income classifications were used for income grouping.ResultsGlobally, there were ~364.58 million prevalent cases (females: 225.16 million), 29.51 million incident cases (females: 17.53 million), and 11.53 million DALYs (females: 7.09 million) due to KOA in 2019. The Western Pacific Region had a high endemicity of ~7,319.87 cases per 100,000 people (7.64%). Japan's prevalence rate (12,610.12 cases per 100,000 population) was 10 times that of Somalia (1,178.23) in 2019. In 200 countries (except the United Arab Emirates), the prevalence, incidence, and DALY rates of KOA in 2019 were higher among females than among males and increased with age up to the oldest age group. The prevalence was highest in the high-middle SDI countries, and the incidence and DALYs were highest in the middle SDI countries.ConclusionThere was a large burden of KOA worldwide, with some notable intercountry variation. Some countries had 10 times the burden of other countries. Increasing population awareness regarding the prevalence, incidence, and DALYs of KOA with a focus on the population in the Western Pacific Region is needed, particularly for older females. informs health policy development, and contributes to improving the efficiency, equity, and effectiveness of healthcare systems.

Atmospheric aerosols play a pivotal role in the earth-atmospheric system. Analyzing their optical properties, specifically absorption and scattering coefficients, is essential for comprehending the impact of aerosols on climate. When different optical properties of aerosols are individually measured using multiple devices, cumulative errors in the detection results inevitably occur. To address this challenge, based on photoacoustic spectroscopy (PAS) and integrating sphere (IS) scattering enhancement, a compact gas cell (PASIS-Cell) was developed. The PASIS-Cell comprises a dual-T-type photoacoustic cell (DTPAC) and an IS. IS is coupled with DTPAC through a transparent quartz tube, thereby enhancing the scattering signal without compromising the acoustic characteristics of DTPAC. Concurrently, DTPAC can realize high-performance photoacoustic detection of absorption signal. Experimental results demonstrate that PASIS-Cell can simultaneously invert atmospheric aerosol absorption and scattering coefficients, with a minimum detection limit of less than 1 Mm−1, showcasing its potential in the analysis of aerosol optical properties.

Abstract Traditional multicast routing strategies can hardly meet the demanding requirements of multicasting mission assignment messages in airborne tactical networks. This letter proposes an intent‐driven routing strategy, termed as IDR, to realize reliable and efficient multicast. IDR exploits bit index explicit replication technique to encode not only the destination information but also the retransmission information into packet headers. If part of the multicast members failed to receive the packet, IDR can perceive the error and retransmit the packet to the precise set of nodes. Compared to the state‐of‐the‐art reliable multicast routing methods, IDR can enhance multicast retransmission success rate by about 10% or more and reduce retransmission overhead by around 50%.

Abstract Cancer remains a global health challenge, demanding early detection and accurate diagnosis for improved patient outcomes. An intelligent paradigm is introduced that elevates label‐free nonlinear optical imaging with contrastive patch‐wise learning, yielding stain‐free nonlinear optical computational histology (NOCH). NOCH enables swift, precise diagnostic analysis of fresh tissues, reducing patient anxiety and healthcare costs. Nonlinear modalities are evaluated, including stimulated Raman scattering and multiphoton imaging, for their ability to enhance tumor microenvironment sensitivity, pathological analysis, and cancer examination. Quantitative analysis confirmed that NOCH images accurately reproduce nuclear morphometric features across different cancer stages. Key diagnostic features, such as nuclear morphology, size, and nuclear‐cytoplasmic contrast, are well preserved. NOCH models also demonstrate promising generalization when applied to other pathological tissues. The study unites label‐free nonlinear optical imaging with histopathology using contrastive learning to establish stain‐free computational histology. NOCH provides a rapid, non‐invasive, and precise approach to surgical pathology, holding immense potential for revolutionizing cancer diagnosis and surgical interventions.

Abstract Background Uric acid/high-density lipoprotein cholesterol ratio (UHR) is a novel index of inflammation and metabolism that has been investigated in various diseases. However, association between UHR and hypertension among reproductive-aged women is unclear. Methods In this cross-sectional study, we investigated the association between serum UHR and hypertension among 5485 women aged 20–44 years based on the National Health and Nutrition Examination Survey (NHANES) database using various methods, including univariate and multivariate logistic regression analysis, stratified analysis, and spline regression. P 1, P

Abstract Chemotherapy can cause ovarian dysfunction and infertility since the ovary is extremely sensitive to chemotherapeutic drugs. Apart from the indispensable role of the ovary in the overall hormonal milieu, ovarian dysfunction also affects many other organ systems and functions including sexuality, bones, the cardiovascular system, and neurocognitive function. Although conventional hormone replacement therapy can partly relieve the adverse symptoms of premature ovarian insufficiency (POI), the treatment cannot fundamentally prevent deterioration of POI. Therefore, effective treatments to improve chemotherapy-induced POI are urgently needed, especially for patients desiring fertility preservation. Recently, mesenchymal stem cell (MSC)-based therapies have resulted in promising improvements in chemotherapy-induced ovary dysfunction by enhancing the anti-apoptotic capacity of ovarian cells, preventing ovarian follicular atresia, promoting angiogenesis and improving injured ovarian structure and the pregnancy rate. These improvements are mainly attributed to MSC-derived biological factors, functional RNAs, and even mitochondria, which are directly secreted or indirectly translocated with extracellular vesicles (microvesicles and exosomes) to repair ovarian dysfunction. Additionally, as a novel source of MSCs, menstrual blood-derived endometrial stem cells (MenSCs) have exhibited promising therapeutic effects in various diseases due to their comprehensive advantages, such as periodic and non-invasive sample collection, abundant sources, regular donation and autologous transplantation. Therefore, this review summarizes the efficacy of MSCs transplantation in improving chemotherapy-induced POI and analyzes the underlying mechanism, and further discusses the benefit and existing challenges in promoting the clinical application of MenSCs in chemotherapy-induced POI.

Abstract Background Serum uric acid levels are higher in patients with type 2 diabetes and prediabetes compared to healthy individuals, and hyperuricemia causes a significant rate of complications and mortality through heart and kidney diseases. Accordingly, the present systematic review and meta-analysis aimed to investigate the effect of empagliflozin on serum uric acid levels. Materials and methods Electronic databases, including PubMed, Scopus, Web of Science, Cochrane, and Google Scholar, were used to search papers until May 22, 2023. Data analysis was conducted by STATA Version 14, and P-value

Abstract Aims Chronic heart failure (CHF) remains a major health issue worldwide. In the present study, we aimed to identify novel circulating biomarkers for CHF using serum proteomics technology and to validate the biomarker in three independent cohorts. Methods and results The isobaric tags for relative and absolute quantitation technology was utilized to identify the potential biomarkers of CHF. The validation was conducted in three independent cohort. Cohort A included 223 patients with ischaemic heart disease (IHD) and 321 patients with ischaemic heart failure (IHF) from the CORFCHD‐PCI study. Cohort B recruited 817 patients with IHD and 1139 patients with IHF from the PRACTICE study. Cohort C enrolled 559 non‐ischaemic heart disease patients with CHF (n = 316) or without CHF (n = 243). We found the expression of a‐1 antitrypsin (AAT) was elevated significantly in patients with CHF compared with that in the patients with stable IHD using statistical and bioinformatics analyses. In a validation study, there was a significant difference between patients with stable IHD and patients with IHF in AAT concentration either in cohort A (1.35 ± 0.40 vs. 1.64 ± 0.56, P

Scuticociliates are recognized as the causative agents of mass mortalities in certain cultured marine fishes, resulting in enormous economic losses. This study aimed to investigate a fatal infection caused by scuticociliates in farmed large yellow croaker (Larimichthys crocea) in Fujian province, China. Microscopic examinations of focal organs, including the brain, eyes, gills, and skin, revealed the presence of parasites. Active masses of scuticociliates were observed in these organs, and the ciliates were subsequently isolated and maintained in vitro. An immersion challenge experiment revealed that L. crocea experienced cumulative mortalities reaching 73% within 7 d upon exposure to 1.0 × 104 ciliates mL−1. Based on the microscopic and PCR testing of infected fishes, the brain was comprehensively inferred as the main infection organ for the isolated strain. Microscopic and submicroscopic observations of the isolated scuticociliate, coupled with cortical ciliature patterns revealed through α-tubulin indirect immunofluorescence techniques, identified these scuticociliates as Miamiensis avidus. The sequencing of two genetic markers (small subunit ribosomal RNA, SSU rRNA and cytochrome c oxidase subunit I, COI) further confirmed that the isolated strains exhibited the highest sequence similarity to most M. avidus sequences in GenBank. However, significant differences in SSU sequences compared to the M. avidus strain Ma/2, and the lack of published COI and ITS (internal transcribed spacer) sequences for Ma/2, indicate the need for further molecular data to resolve whether there are potential cryptic species within the M. avidus complex.

Background: It is crucial to accurately predict the disease progression of systemic arterial hypertension in order to determine the most effective therapeutic strategy. To achieve this, we have employed a multimodal data-integration approach to predict the longitudinal progression of new-onset systemic arterial hypertension patients with suspected obstructive sleep apnea (OSA) at the individual level. Methods: We developed and validated a predictive nomogram model that utilizes multimodal data, consisting of clinical features, laboratory tests, and sleep monitoring data. We assessed the probabilities of major adverse cardiac and cerebrovascular events (MACCEs) as scores for participants in longitudinal cohorts who have systemic arterial hypertension and suspected OSA. In this cohort study, MACCEs were considered as a composite of cardiac mortality, acute coronary syndrome and nonfatal stroke. The least absolute shrinkage and selection operator (LASSO) regression and multiple Cox regression analyses were performed to identify independent risk factors for MACCEs among these patients. Results: 448 patients were randomly assigned to the training cohort while 189 were assigned to the verification cohort. Four clinical variables were enrolled in the constructed nomogram: age, diabetes mellitus, triglyceride, and apnea-hypopnea index (AHI). This model accurately predicted 2-year and 3-year MACCEs, achieving an impressive area under the receiver operating characteristic (ROC) curve of 0.885 and 0.784 in the training cohort, respectively. In the verification cohort, the performance of the nomogram model had good discriminatory power, with an area under the ROC curve of 0.847 and 0.729 for 2-year and 3-year MACCEs, respectively. The correlation between predicted and actual observed MACCEs was high, provided by a calibration plot, for training and verification cohorts. Conclusions: Our study yielded risk stratification for systemic arterial hypertension patients with suspected OSA, which can be quantified through the integration of multimodal data, thus highlighting OSA as a spectrum of disease. This prediction nomogram could be instrumental in defining the disease state and long-term clinical outcomes.

Kidney diseases are important diseases that affect human health worldwide. According to the 2020 World Health Organization (WHO) report, kidney diseases have become the top 10 causes of death. Strengthening the prevention, primary diagnosis, and action of kidney-related diseases is of great significance in maintaining human health and improving the quality of life. It is increasingly challenging to address clinical needs with the present technologies for diagnosing and treating renal illness. Fortunately, metal-organic frameworks (MOFs) have shown great promise in the diagnosis and treatment of kidney diseases. This review summarizes the research progress of MOFs in the diagnosis and treatment of renal disease in recent years. Firstly, we introduce the basic structure and properties of MOFs. Secondly, we focus on the utilization of MOFs in the diagnosis and treatment of kidney diseases. In the diagnosis of kidney disease, MOFs are usually designed as biosensors to detect biomarkers related to kidney disease. In the treatment of kidney disease, MOFs can not only be used as an effective adsorbent for uremic toxins during hemodialysis but also as a precise treatment of intelligent drug delivery carriers. They can also be combined with nano-chelation technology to solve the problem of the imbalance of trace elements in kidney disease. Finally, we describe the current challenges and prospects of MOFs in the diagnosis and treatment of kidney diseases.

Abstract Background Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of chronic kidney disease (CKD). Estimation of mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing mitochondrial function in large samples. However, no study has investigated the association between mtDNA-CN and CKD in older adults with the highest prevalence. The objective is to examine cross-sectional and prospective associations between mtDNA-CN values and CKD risk in older adults to determine whether mtDNA-CN represents a novel potential biomarker for the recognition of CKD risk. Patients and methods In a Chinese community-based cohort of over 65-year-olds, we included 14,467 participants (52.6% females). CKD was defined by eGFR

Abstract Background There is an urgent need to learn more about the epidemiological features of dyslipidemia in youth to address the high burden of cardiovascular disease. Methods This experiment was an observational, cross-sectional study. The samples were collected from 22,379 college students at Xinjiang Medical University. Result The overall prevalence of dyslipidemia was 13.17%, which was significantly higher in men (23%) than in women (7.2%), p

Abstract Background Trichomonas vaginalis is a widespread and important sexually transmitted pathogen. Adherence to the surface of the host cell is the precondition for the parasitism and pathogenicity of this parasite. Trichomonas vaginalis adhesion protein 33 (TvAP33) plays a key role in the process of adhesion, but how this protein mediates the adhesion and pathogenicity of T. vaginalis to host cells is unclear. Methods The expression of TvAP33 in trophozoites was knocked down by small interfering RNA. VK2/E6E7 cells and mice infected with T. vaginalis were used to evaluate the pathogenicity of T. vaginalis. We constructed a complementary DNA library of VK2/E6E7 cells and screened the protein molecules interacting with TvAP33 by the yeast two-hybrid system. The interaction between TvAP33 and BNIP3 (Bcl-2 interacting protein 3) was analyzed by co-immunoprecipitation and colocalization. Results Following knockdown of TvAP33 expression, the number of T. vaginalis trophozoites adhering to VK2/E6E7 cells decreased significantly, and the inhibition of VK2/E6E7 cell proliferation and VK2/E6E7 cell apoptosis and death induced by T. vaginalis were reduced. Animal challenge experiments showed that the pathogenicity of trophozoites decreased following passive immunization with TvAP33 antiserum or blocking of the TvAP33 protein. Immunofluorescence analysis revealed that TvAP33 could bind to VK2/E6E7 cells. Eighteen protein molecules interacting with TvAP33 were identified by the yeast two-hybrid system. The interaction between TvAP33 and BNIP3 was further confirmed by co-immunoprecipitation and colocalization. When the expression of both TvAP33 and BNIP3 in trophozoites was knocked down by small RNA interference, the number of T. vaginalis adhering to VK2/E6E7 cells and the inhibition of VK2/E6E7 cell proliferation were significantly lower compared to trophozoites with only knockdown of TvAP33 or only BNIP3. Therefore, the interaction of TvAP33 and BNIP3 in the pathogenesis of T. vaginalis infecting host cells is not unique and involves other molecules. Conclusions Our study showed that the interaction between TvAP33 and BNIP3 mediated the adhesion and pathogenicity of T. vaginalis to host cells, providing a basis for searching for drug targets for T. vaginalis as well as new ideas for the prevention and treatment of trichomoniasis. Graphical Abstract

BackgroundMany previous studies have revealed a close relationship between lipoprotein metabolism and sepsis, but their causal relationship has, until now, remained unclear. Therefore, we performed a two-sample Mendelian randomization analysis to estimate the causal relationship of lipoprotein-associated phospholipids with the risk of sepsis.Materials and methodsA two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between lipoprotein-associated phospholipids and sepsis based on large-scale genome-wide association study (GWAS) summary statistics. MR analysis was performed using a variety of methods, including inverse variance weighted as the primary method, MR Egger, weighted median, simple mode, and weighted mode as complementary methods. Further sensitivity analyses were used to test the robustness of the data.ResultsAfter Bonferroni correction, the results of the MR analysis showed that phospholipids in medium high-density lipoprotein (HDL; ORIVW = 0.82, 95% CI 0.71-0.95, P = 0.0075), large HDL (ORIVW = 0.92, 95% CI 0.85-0.98, P = 0.0148), and very large HDL (ORMR Egger = 0.83, 95% CI 0.72-0.95, P = 0.0134) had suggestive causal relationship associations with sepsis. Sensitivity testing confirmed the accuracy of these findings. There was no clear association between other lipoprotein-associated phospholipids and sepsis risk.ConclusionsOur MR analysis data suggestively showed a correlation between higher levels of HDL-associated phospholipids and reduced risk of sepsis. Further studies are required to determine the underlying mechanisms behind this relationship.

Instructional quality assessment is a systematic project involving a wide range. Restricted and influenced by many factors and conditions. How to accurately and effectively assess the instructional quality of teachers. The determination of the assessment system and method is very important. Some people think that the quality of teaching is “the total of the characteristics of tertiary education that can meet the obvious or implicit needs of individuals, groups, and society. These characteristics are shown through the goals, standards, and achievement levels required by the educated, educators, and social development. In this article, a back propagation neural network (BPNN) is used in classroom instructional quality assessment, and a classroom instructional quality assessment model is constructed. The experimental results of this article show that the accuracy rate of the algorithm based on BPNN reaches 89%, and the learning rate reaches 93%.

Background. Cellular senescence is thought to play a significant role in the onset and development of diabetic nephropathy. The goal of this study was to explore potential biomarkers associated with diabetic glomerulopathy from the perspective of senescence. Methods. Datasets about human glomerular biopsy samples related to diabetic nephropathy were systematically obtained from the Gene Expression Omnibus database. Hub senescence-associated genes were investigated by differential gene analysis and Least Absolute Shrinkage and Selection Operator analysis. Cluster analysis was employed to identify senescence molecular subtypes. A single-cell dataset was used to validate the above findings and further evaluate the senescence environment. The relationship between these genes and the glomerular filtration rate was explored based on the Nephroseq database. These gene expressions have also been explored in various kidney diseases. Results. Twelve representative senescence-associated genes (VEGFA, IQGAP2, JUN, PLAT, ETS2, ANG, MMP14, VEGFC, SERPINE2, CXCR2, PTGES, and EGF) were finally identified. Biological changes in immune inflammatory response, cell cycle regulation, metabolic regulation, and immune microenvironment have been observed across different molecular subtypes. The above results were also validated based on single-cell analysis. Additionally, we also identified several significantly altered cell communication pathways, including COLLAGEN, PTN, LAMININ, SPP1, and VEGF. Finally, almost all these genes could well predict the occurrence of diabetic glomerulopathy based on receiver operating characteristic analysis and are associated with the glomerular filtration rate. These genes are differently expressed in various kidney diseases. Conclusion. The present study identified potential senescence-associated biomarkers and further explored the heterogeneity of diabetic glomerulopathy that might provide new insights into the diagnosis, assessment, management, and personalized treatment of DN.

BackgroundPrediabetes is associated with an increased risk of cardiovascular diseases and all-cause mortality. Rare research in China has evaluated the prevalence of prediabetes among children and adolescents using the HbA1c criterion or the combined FPG-or-HbA1c diagnostic criterion, and researchers paid no attention to the distributions of blood glucose in Shenzhen, especially for juveniles.MethodsWe conducted a school-based cross-sectional study based on the first-year students from 17 primary, middle, and high schools. Prediabetes was defined as FPG of 5.6–6.9 mmol/L or HbA1c of 5.7%–6.4%. The crude and standardized prevalence of prediabetes with 95% confidence interval (95% CI) was estimated.ResultsA total of 7519 participants, aged 6 to 17 years, were included. For all subjects, the crude prevalence (95% CI) of prediabetes was 1.49% (1.21–1.77), 8.72% (8.08–9.36), and 9.80% (9.13–10.47) by the FPG-only, HbA1c-only, and FPG-or-HbA1c criteria, respectively. Based on the 2010 Shenzhen census population, the standardized prevalence was 1.56% (males 1.85%, females 1.19%), 11.05% (males 11.47%, females 10.53%), and 12.19% (males 13.01%, females 11.15%) by the corresponding criteria. The proportion of prediabetes was higher for males than females, and the prevalence decreased with grade for males but increased for females. The association of BMI and prediabetes was U-shaped curve, indicating higher rates of prediabetes for underweight and obesity people.ConclusionThe blood glucose status of children and adolescents in Shenzhen is worrisome, and the early detection and management of prediabetes are imperative.

ObjectiveOsteoarthritis (OA) is associated with cardiovascular disease and represents a persistent economic and physical burden on patients in the United States. This study evaluated the mediating effect of dietary live microbe intake on the association between cardiovascular health [based on Life's Essential 8 (LE8) scores] and osteoarthritis (OA) in adults.MethodsThis cross-sectional study included data from the National Health and Nutrition Examination Survey, 1999–2019 (from patients aged ≥20 years). LE8 scores (0–100) were measured according to the American Heart Association definition and categorized as low (0–49), moderate (50–79), or high (80–100). OA disease status was assessed using self-reported data from patients. The relationships were evaluated using multivariate logistic and restricted cubic spline models. Mediation analysis was used to evaluate the mediating effect of dietary live microbe intake on the association between LE8 and OA risk.ResultsThe study included 23,213 participants aged ≥20 years. After adjusting for latent confounders, higher LE8 scores were found to be associated with a lower incidence of OA. The odds ratios (with 95% confidence intervals) for low, moderate, and high OA risk were 0.81 (0.69, 0.96) and 0.55 (0.44, 0.69), respectively; a non-linear dose-response relationship was observed (P-nonlinear = 0.012). Health behavior and health factor scores showed a similar pattern of correlation with OA risk. Low live microbe intake mediated the association between LE8, health behavior, and health factor scores with OA risk and did not appear to reduce OA risk.ConclusionOur findings suggest that although higher LE8 scores reduce the risk of developing OA, low live microbe intake may reduce the protective effect of higher scores. It is, therefore, essential to emphasize adherence to a lifestyle that confers high LE8 scores. Individuals should also be advised to reduce the intake of foods with low live microbe content.

Triple-negative breast cancer (TNBC) is the most refractory subtype of breast cancer, and effective treatments are urgently needed owing to its poor prognosis. Surgery, radiotherapy, and chemotherapy, alone or in combination, are the leading choices for TNBC therapy. Although promising approaches and procedures have emerged, several challenges, such as off-target effects, drug resistance, and severe side effects, remain to be addressed. Recently, transient receptor potential channel mucolipin 1 (TRPML1) has attracted the attention of researchers because its expression has been implicated in numerous diseases, including cancer. TRPML1 regulates biological events and signaling pathways, including autophagic flux, exocytosis, ionic homeostasis, and lysosomal biogenesis, all contributing to tumorigenesis and cancer progression. TRPML1 also functions as a building block for cancer cell growth, mitogenic signaling, priming tissues for metastasis, and activation of transcriptional programs, processes involved in several malignant tumors. This review provides an overview of breast cancer epidemiology and diagnostic techniques and then discusses the existing therapeutics. Additionally, we elaborate on the development of, and associated challenges to, TNBC diagnostics and treatment and the feasibility of TRPML1 as a therapeutic target for TNBC.

The escalating prevalence of hyperlipidemia has a profound impact on individuals' daily physiological well-being. The traditional Chinese medicine (TCM) prescription Danggui Shaoyao San (DSS) has demonstrated significant clinical efficacy and promising prospects for clinical application. Leveraging network pharmacology and bioinformatics, we hypothesize that DSS can ameliorate lipid metabolic disorders in hyperlipidemia by modulating the PPAR signaling pathway. In this study, we employed a zebrafish model to investigate the impact of DSS on lipid metabolism in hyperlipidemia. Body weight alterations were monitored by pre- and postmodeling weight measurements. Behavioral assessments and quantification of liver biochemical markers were conducted using relevant assay kits. Pathways associated with lipid metabolism were identified through network pharmacology and GEO analysis, while PCR was utilized to assess genes linked to lipid metabolism. Western blotting was employed to analyze protein expression levels, and liver tissue underwent Oil Red O and immunofluorescence staining to evaluate liver lipid deposition. Our findings demonstrate that DSS effectively impedes weight gain and reduces liver lipid accumulation in zebrafish models with elevated lipid levels. The therapeutic effects of DSS on lipid metabolism are mediated through its modulation of the PPAR signaling pathway, resulting in a significant reduction in lipid accumulation within the body and alleviation of certain hyperlipidemia-associated symptoms.

Partitioning the contributions of climate, economic growth, and policy to a region’s carbon flows is an important process for the Chinese government seeking to optimize their regional development policies to achieve carbon neutrality by 2060. A combination of the carbon emission analysis and human appropriation of net primary production (HANPP) framework was applied to a village in the Lhasa river valley, Tibet, to quantify the contributions of these different factors to carbon flows and neutrality. From 2010 to 2019, the average annual net sequestration of CO2 was 374.9 g CO2 m−2 a−1. Changes in climate conditions and the regional policy of Grassland Ecological Protection Subsidy and Reward increased carbon sequestrations by 409.5 and 25.7 g CO2 m−2 a−1, respectively. Socioeconomic development, policies for reducing poverty, and promotion of forage production led to the increase in CO2 emissions by 103.5, 88.8, and 4.3 g CO2 m−2 a−1, respectively. The cumulative CO2 emissions (including HANPP) caused by land use were 298.92 Tg CO2 (2479.63 g CO2 m−2; 1 Tg = 1012 g), while the cumulative CO2 emissions due to energy use were only 11.22 Tg CO2 (93.07 g CO2 m−2), equal to 3.75% of the CO2 emissions driven by land use. Livestock grazing and cropland cultivation were the two main land use factors affecting the carbon balance. We argue that unhooking economic growth from traditional nomadic animal husbandry and lifestyles through policy optimizations would highly contribute the carbon neutrality in Tibet.

It is particularly important to establish more effective and safer antiplatelet treatment strategies according to age. The present subanalysis of the PATH-PCI trial was to determine the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy in different age groups. We randomized 2285 chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) into a standard group or a personalized group from December 2016 to February 2018. The personalized group received personalized antiplatelet therapy (PAT) based on a novel platelet function test (PFT). The standard group received standard antiplatelet therapy (SAT). Then, all patients were divided according to age (under the age of 65 years and aged 65 years or over) to investigate the association and interaction of age on clinical outcomes at 180 days. In the patients under the age of 65 years, the incidence of NACEs was decreased in the personalized group compared to the standard group (5.1% vs. 8.8%, HR: 0.603, 95% CI: 0.409–0.888, P = .010). The rates of MACCEs (3.3% vs. 7.7%, HR: 0.450, 95% CI: 0.285–0.712, P = .001), MACEs (2.2% vs. 5.4%, HR: 0.423, 95% CI: 0.243–0.738, P = .002) also decreased. We did not find a significant difference in bleeding between the groups. In the patients aged 65 years or over, no difference in the primary endpoint was found (4.9% vs. 4.2%, P = .702), and comparable rates of survival were observed with the two strategies (all Ps > 0.05). The present study shows that PAT according to PFT was comparable to SAT at the 180-day follow-up for both ischemic and bleeding endpoints in CCS patients aged 65 years or over who underwent PCI. In patients under the age of 65 years, PAT can reduce ischemic events but does not increase bleeding, and it is an effective and safe treatment strategy. It may be necessary for young CCS patients after PCI to undergo PAT early after PCI.

Kabuki syndrome (KS) is a rare multisystem-affecting genetic disorder, and usually accompanied with autoimmune disorders such as immune thrombocytopenic purpura (ITP). Here, we report a 16-year-old patient with Kabuki syndrome with ITP and observe the therapeutic effect of TPO agonist hetrombopag olamine tablets. The duration of maintenance therapy and follow up were both 17 months. Whole exon sequencing (WES) of the patient’s peripheral blood showed c.5775_5778del (p. Leu1926LysfsTer120) heterozygous mutation in the KMT2D gene, which was not reported before.

Abstract Chemotherapy was conventionally applied to kill cancer cells, but regrettably, they also induce damage to normal cells with high-proliferative capacity resulting in cardiotoxicity, nephrotoxicity, peripheral nerve toxicity, and ovarian toxicity. Of these, chemotherapy-induced ovarian damages mainly include but are not limited to decreased ovarian reserve, infertility, and ovarian atrophy. Therefore, exploring the underlying mechanism of chemotherapeutic drug-induced ovarian damage will pave the way to develop fertility-protective adjuvants for female patients during conventional cancer treatment. Herein, we firstly confirmed the abnormal gonadal hormone levels in patients who received chemotherapy and further found that conventional chemotherapeutic drugs (cyclophosphamide, CTX; paclitaxel, Tax; doxorubicin, Dox and cisplatin, Cis) treatment significantly decreased both the ovarian volume of mice and the number of primordial and antral follicles and accompanied with the ovarian fibrosis and reduced ovarian reserve in animal models. Subsequently, Tax, Dox, and Cis treatment can induce the apoptosis of ovarian granulosa cells (GCs), likely resulting from excessive reactive oxygen species (ROS) production-induced oxidative damage and impaired cellular anti-oxidative capacity. Thirdly, the following experiments demonstrated that Cis treatment could induce mitochondrial dysfunction through overproducing superoxide in GCs and trigger lipid peroxidation leading to ferroptosis, first reported in chemotherapy-induced ovarian damage. In addition, N-acetylcysteine (NAC) treatment could alleviate the Cis-induced toxicity in GCs by downregulating cellular ROS levels and enhancing the anti-oxidative capacity (promoting the expression of glutathione peroxidase, GPX4; nuclear factor erythroid 2-related factor 2, Nrf2 and heme oxygenase-1, HO-1). Our study confirmed the chemotherapy-induced chaotic hormonal state and ovarian damage in preclinical and clinical examination and indicated that chemotherapeutic drugs initiated ferroptosis in ovarian cells through excessive ROS-induced lipid peroxidation and mitochondrial dysfunction, leading to ovarian cell death. Consequently, developing fertility protectants from the chemotherapy-induced oxidative stress and ferroptosis perspective will ameliorate ovarian damage and further improve the life quality of cancer patients.

Abstract Background Functional constipation (FC) in children affects their growth, development and quality of life. L-pipecolic acid (L-PA) was decreased in FC children based on gut microbiome and serum metabolomic. In this study, loperamide-induced constipation in mice was used to evaluate the effects of L-PA on constipated mice. Method 26 FC and 28 healthy children were recruited. Stool samples and serum samples were subjected to 16S rDNA sequencing and ultra-performance liquid chromatography/quadrupole time of flight (UPLC-Q/TOF-MS) approach, respectively. A loperamide-induced mouse constipation model was developed, and all mice were randomly divided into control (Con), loperamide (Lop) and L-PA (Lop + L-PA) treatment groups (6 mice per group). The mice in the Lop + L-PA group were given L-PA (250 mg/kg, once a day) and loperamide; the Lop group was given loperamide for 1 week, and the Con group was given saline. The fecal parameters and intestinal motility of mice in each group were detected. serum 5-HT levels and colon 5-HT expression were detected by ELISA and immunohistochemistry, respectively; qRT-PCR was used to detect the expression of AQP3 and 5-HT4R mRNA in each group. Results 45 differential metabolites and 18 significantly different microbiota were found in FC children. The α and β diversity of gut microbiota in FC children was significantly reduced. Importantly, serum L-PA was significantly reduced in FC children. The KEGG pathway enrichment were mainly enriched in fatty acid biosynthesis, lysine degradation, and choline metabolism. L-PA was negatively associated with Ochrobactrum, and N6, N6, N6-trimethyl-l-lysine was positively associated with Phascolarcrobacterium. In addition, L-PA improved the fecal water content, intestinal transit rate, and increased the serum 5-HT levels in constipated mice. Moreover, L-PA increased the expression of 5-HT4R, reduced AQP3, and regulated constipation-associated genes. Conclusions Gut microbiota and serum metabolites were significantly altered in children with FC. The abundance of Phascolarctobacterium and Ochrobactrum and serum L-PA content were decreased in FC children. L-PA was found to alleviate the fecal water content, increase intestinal transit rate and the first black stool defecation time. L-PA improved constipation by increasing 5-HT and 5-HT4R expression while down-regulating AQP3 expression.