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Endocervical adenocarcinoma (ECA) is reported increasingly often in young women, and this aggressive disease lacks effective methods of targeted therapy. Since mismatch repair deficiency (dMMR) is an important biomarker for predicting response to immune checkpoint inhibitors, it is important to investigate the clinicopathological features and immune microenvironment of dMMR ECAs. We assessed 617 ECAs from representative tissue microarray sections, gathered clinicopathologic information, reviewed histological characteristics, and performed immunohistochemical staining for MMR, programmed cell death 1 (PD-L1), and other immune markers. Of 617 ECA samples, 20 (3.2%) cases had dMMR. Among them, loss of MMR-related proteins expression was observed in 17/562 (3.0%) human papilloma virus-associated (HPVA) adenocarcinoma and 3/55 (5.5%) non-HPV-associated (NHPVA) adenocarcinoma. In NHPVA cohort, dMMR status was observed in 3 (3/14, 15.0%) patients with clear cells. dMMR ECAs had a higher tendency to have a family history of cancer, larger tumor size, p16 negative, HPV E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) negative, and lower ki-67 index. Among the morphological variables evaluated, poor differentiation, necrosis, stromal tumor-infiltrating lymphocytes, peritumoral lymphocytes, and lymphoid follicles were easily recognized in the dMMR ECAs. In addition, dMMR ECAs had higher CD3+, CD8+, CD38+, CD68+ and PD-1+ immune cells. A relatively high prevalence of PD-L1 expression was observed in dMMR ECAs. dMMR ECAs were significantly more likely to present with a tumor-infiltrating lymphocytes -high/PD-L1-positive status. In conclusion, dMMR ECAs have some specific morphological features and a critical impact on the immune microenvironment, which may provide insights into improving responses to immunotherapy-included comprehensive treatment for ECAs in the future.
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Green manure is a crucial strategy for increasing cereal yield and mitigating environmental burden while reducing chemical N fertilizer. To effectively tackle climate change, finding ways to reduce nitrous oxide (N2O) emissions from green manuring systems is vital. Herein, field and 15N labeled microcosm experiments were arranged to investigate the effect and mechanisms of green manuring and zeolite application on N2O emission. Both experiments comprised four treatments: conventional chemical N (N100), 70â¯% chemical N (N70), N70 with green manure (N70â¯+â¯CV), and N70â¯+â¯CV combined with zeolite (N70â¯+â¯CVâ¯+â¯Z). Compared with N100, both N70â¯+â¯CV and N70â¯+â¯CVâ¯+â¯Z maintained maize yield, cumulative N2O emissions decreased by 37.7â¯% and 34.9â¯% in N70â¯+â¯CVâ¯+â¯Z in 2022-yr and 2023-yr, and by 12.8â¯% in N70â¯+â¯CV in 2022-yr. Moreover, the reduction of N2O emission primarily occurred after incorporating green manure. The N100 and N70â¯+â¯CV demonstrated a similar transformed proportion of chemical N to N2O (i.e., 4.9â¯% and 4.7â¯%) while reducing it to 2.7â¯% in N70â¯+â¯CVâ¯+â¯Z. Additionally, a mere 0.7â¯% of green manure N was transformed to N2O in both N70â¯+â¯CV and N70â¯+â¯CVâ¯+â¯Z treatments. Compared with N100, both N70â¯+â¯CV and N70â¯+â¯CVâ¯+â¯Z decreased the relative abundances of ammonia oxidation microbes, increased denitrifier and the ratios of (nirKâ¯+â¯nirS)/nosZ and norBC/nosZ. Furthermore, compared with N70â¯+â¯CV, N70â¯+â¯CVâ¯+â¯Z decreased the relative abundances of N2O-producer and the ratios of (nirKâ¯+â¯nirS)/nosZ and norBC/nosZ in denitrification. These findings revealed that the reduction of N2O emissions resulting from green manure replaced chemical N was mainly due to weakened nitrification, while zeolite reduced N2O emissions attributed to enhanced conversion of N2O to N2. Moreover, certain key N-cycling functional bacteria, such as Phycisphaerae, Rubrobacteria, and Thermoflexia, were positively correlated with N2O emission. In contrast, Dehalococcoidia, Gammaproteobacteria, and Betaproteobacteria were negatively correlated with N2O emission. This investigation uncovered the underlying mechanisms for effectively reducing N2O emissions through green manure combined with zeolite.
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Due to the fact that more conventional heavy oil recovery methods (heating, emulsification, dilution, and other methods) have many shortcomings, they cannot meet the demand of heavy oil exploitation. Therefore, there is a need for new recovery methods. In this paper, the surface of nano SiO2 was modified with a silane coupling agent, KH-560, to prepare a nanoviscosity reducer (NRV), which has high-temperature resistance (300 °C), calcium and magnesium resistance (Ca2+ + Mg2+ > 900 mg/L) and high viscosity reduction rate (>99%). FTIR and SEM measurements showed that KH560 has been successfully connected to the surface of SiO2. The particle size distribution of NRV is mainly distributed in 50-80 nm, which matches the results of SEM. The experimental results showed that the viscosity reduction rates of 1 wt % NRV on M-1 heavy oil before and after aging were 99.73% and 99.71%, respectively. The viscosity reduction effect of 1% NRV on M-1 heavy oil and the bleeding rate of emulsion formation were investigated when the oil-water ratio ranged from 9:1 to 1:9. The results showed that when the oil-water ratio was between 7:3 and 1:9, the viscosity reduction rate was greater than 99%. Besides, the bleeding rate of emulsion increases with the decrease of the oil-water ratio. What's more, static and dynamic adsorption experiments showed that the adsorption capacity of 1 wt % NRV was 1.746 mg/g and 1.668 mg/g sand, respectively. The interfacial tension experiment showed that the interfacial tension (IFT) between 1 wt % NRV and M-1 heavy oil was 0.052 mN/m, and low interfacial tension was beneficial to displace the oil in the formation pores. At the same time, the displacement effect of NRV on M-1 heavy oil at different concentrations (0.5, 1.0, and 1.5 wt %) and temperatures (200, 250, and 300 °C) was investigated by core flooding experiments. The results showed that the recovery rate increases with the increase of NRV concentration, and 1 wt % NRV at 300 °C will improve the recovery rate of M-1 heavy oil by 27.3% compared to steam flooding. NRV could reduce the viscosity of crude oil, which provides technical guidelines for the exploitation of heavy oil and extra heavy oil.
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OBJECTIVE: To examine the association between preovulation body mass index and pregnancy outcomes after frozen embryo transfer in patients with polycystic ovary syndrome with insulin resistance. DESIGN: This was a single-center, retrospective cohort study. SUBJECTS: Women with infertility, diagnosed with polycystic ovary syndrome and insulin resistance, and treated at the Reproductive Medicine Center, Second People's Hospital of Nanning, China, between January 2020 and August 2023, were included. EXPOSURE: Patients were divided into four groups according to their body mass index (BMI): slim (<18.5 kg/m2), normal (18.5≤ BMI <24 kg/m2), overweight (24≤ BMI <28 kg/m2), or obese (≥28 kg/m2). MAIN OUTCOME MEASURES: The main pregnancy outcomes included rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy. RESULTS: In total, 282 eligible patients were included. A linear association was observed between the BMI and clinical pregnancy outcomes of the first frozen embryo transfer (P for nonlinearity>0.05). After accounting for all potential variables, each 1 kg/m2 increase in BMI was linked to a 2% decrease in the embryo implantation rate (P<0.05), 11% decrease in the frequency of biochemical pregnancy (P<0.05), and 9% decrease in the both clinical (P<0.05) and ongoing pregnancy rates. CONCLUSION: In patients with polycystic ovary syndrome and insulin resistance, a higher BMI was associated with lower rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy.
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The closed nutrient solution management method allows for the recycling and utilization of nutrient solutions, improving the efficiency of water and fertilizer utilization. This study was conducted to investigate the effects of changing the frequency of nutrient solution renewal and method of nutrient supply on the microbial communities composition, yield, and quality in closed soilless systems by using high-throughput sequencing technology and combining the physicochemical properties of root exudate solution. The results showed that different nutrient solution management modes had a significant impact on the structure and diversity of root exudate solution microbial communities. The abundance and diversity of microorganisms in inorganic perlites were correlative with EC. The abundance and diversity of bacterial communities in the root exudate solution of open liquid supply (CK) were higher than that of closed liquid supply, while the abundance and diversity of fungal communities in the root exudate solution of closed liquid supply (T1, T2, T3) were higher than that of open liquid supply. As the frequency of nutrient solution interval decreased, the accumulation of salt in root exudate solution and the richness and diversity of the fungal community also decreased, especially increasing the K+, Ca2+, and Mg2+ contents, which were positively correlated with potential beneficial Candidatus_Xiphinematobacter, Arachidicoccus, Cellvibrio, Mucilaginibacter, Taibaiella communities and decreasing the content of soluble protein, Vitamin C content, but not significantly increased cucumber yield.
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Cucumis sativus , Cucumis sativus/microbiologie , Microbiote , Racines de plante/microbiologie , Nutriments/analyse , Bactéries/métabolisme , Bactéries/classification , Bactéries/génétique , Microbiologie du sol , Champignons , Exsudats végétaux/composition chimique , Engrais/analyseRÉSUMÉ
Silver nanoparticles (AgNPs) have attracted widespread attention in multidrug-resistant bacterial infections. However, the application of AgNPs synthesized by conventional methods is restricted by its high costs, toxicity, and poor stability. Herein, a water-soluble polysaccharide (Scutellaria baicalensis polysaccharide, SBP) rich in reducing sugars was used as both the reductant and stabilizer to greenly synthesize spherical AgNPs@SBP with smaller particle sizes (11.18 ± 2.50 nm) and higher negative zeta potential (-23.05 ± 2.76 mV), which was favorable to enhance its antimicrobial activity and improve pH and thermal stability. Besides, SBP facilitated the adhesion and penetration of AgNPs@SBP to methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli (CREC), thus significantly enhancing its antibacterial activity (increased by 32-fold and 64-fold, respectively). Likewise, AgNPs@SBP at a low concentration (7.8 µg/mL) could effectively penetrate and inhibit nearly 90% of MRSA and CREC biofilm formation. Antimicrobial mechanism studies showed that AgNPs@SBP could lead to more severe cell membrane damage and genetic material leakage by upregulating reactive oxygen species and depolarizing mitochondrial membrane potential, ultimately resulting in the apoptosis of bacteria. Overall, the wrapping of SBP significantly enhanced the antibacterial and antibiofilm activity of AgNPs, which possessed great potential in the prevention and treatment of multidrug-resistant bacterial infections.
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BACKGROUND: There is an increasing number of human immunodeficiency virus (HIV) reported cases among students in Southwest China. However, the data on HIV/sex-related knowledge, attitude toward sex, sexual behaviors, and correlates of pre-exposure prophylaxis (PrEP)-eligible behaviors among college students in this area is still limited. This study aimed to assess the prevalence of HIV/sex-related knowledge, sexual attitudes, sexual behaviors, and factors associated with PrEP-eligible behaviors among college students. METHOD: An online survey from 2020 to 2021 based on a multistage stratified and cluster sampling method was conducted among college students in Southwest China, and a well-designed questionnaire collected data. Propensity score matching (PSM), logistic, and log-binomial regression were used to identify the determinants of PrEP-eligible behaviors. RESULT: A total of 108,987 students participated in the survey, and 92,946 provided valid responses. 91.6% (85,145/92,946) had good HIV-related knowledge, while only 26.0% (24,137/92,946) reported awareness of sex-related knowledge. Furthermore, more than half of the participants (64.5%) held negative stances towards engaging in "one-night stand", and 58.9% (617/1,047) reported PrEP-eligible behaviors. Log-binomial regression analysis indicated that unaware of HIV-related knowledge (aPR = 1.66, 95% CI:1.22-2.26, P = 0.001), not discussing about sex with their parent(s) (aPR = 1.16, 95% CI:1.01-1.33, P = 0.021), not receiving sex-related education in school(aPR = 1.24, 95% CI: 1.07-1.45, P = 0.005), not participating in HIV/AIDS prevention activities in the past year (aPR = 1.32, 95%CI:1.09-1.60, P = 0.004), experiencing forced sex (aPR = 2.08, 95% CI: 1.19-3.63, P = 0.010), and having the drug abuse (aPR = 22.21, 95% CI:5.59-88.31, P < 0.001) were significantly associated with increased odds of PrEP-eligible behaviors. CONCLUSION: College students in Southwest China exhibited suboptimal HIV/sex-related knowledge, received limited sex education, reported conservative attitudes towards casual sex, and significant PrEP-eligible behaviors. These findings suggest that sexually experienced college students who were unaware of HIV-related knowledge, lacked sex education, experienced forced sex, and reported drug abuse were the key individuals for evaluating eligibility for PrEP initiation, and interventions aimed at increasing awareness of HIV/sex-related knowledge, promoting participation in sex education, addressing issues related to forced sex and tackling drug abuse could contribute to reducing the incidence of PrEP-eligible behaviors among college students.
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Infections à VIH , Connaissances, attitudes et pratiques en santé , Prophylaxie pré-exposition , Comportement sexuel , Étudiants , Humains , Mâle , Femelle , Chine/épidémiologie , Infections à VIH/prévention et contrôle , Infections à VIH/épidémiologie , Étudiants/psychologie , Étudiants/statistiques et données numériques , Études transversales , Jeune adulte , Comportement sexuel/statistiques et données numériques , Universités , Enquêtes et questionnaires , Adolescent , AdulteRÉSUMÉ
Although aromatic rings are common elements in pharmaceutically active compounds, the presence of these motifs brings several liabilities with respect to the developability of a drug1. Nonoptimal potency, metabolic stability, solubility and lipophilicity in pharmaceutical compounds can be improved by replacing aromatic rings with non-aromatic isosteric motifs2. Moreover, whereas aromatic rings are planar and lack three-dimensionality, the binding pockets of most pharmaceutical targets are chiral. Thus, the stereochemical configuration of the isosteric replacements may offer an added opportunity to improve the affinity of derived ligands for target receptors. A notable impediment to this approach is the lack of simple and scalable catalytic enantioselective syntheses of candidate isosteres from readily available precursors. Here we present a previously unknown palladium-catalysed reaction that converts hydrocarbon-derived precursors to chiral boron-containing nortricyclanes and we show that the shape of these nortricyclanes makes them plausible isosteres for meta disubstituted aromatic rings. With chiral catalysts, the Pd-catalysed reaction can be accomplished in an enantioselective fashion and subsequent transformation of the boron group provides access to a broad array of structures. We also show that the incorporation of nortricyclanes into pharmaceutical motifs can result in improved biophysical properties along with stereochemistry-dependent activity. We anticipate that these features, coupled with the simple, inexpensive synthesis of the functionalized nortricyclane scaffold, will render this platform a useful foundation for the assembly of new biologically active agents.
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BACKGROUND AND AIMS: Extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short- and long-term outcomes following P-ESWL and ERCP in a large cohort with CP. METHODS: Patients with painful CP and pancreatic stones >5 mm in size, who underwent P-ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective-prospective mixed observational study. The total stone clearance rates were recorded. All patients were followed up until the end of March 2024, with the visual analogue scale (VAS) for pain, pain type, quality-of-life scores and other relevant information recorded. RESULTS: A total of 2071 patients underwent P-ESWL, and 93.1% of them subsequently underwent ERCP during the study period. Patients were followed up for an average of 11.8 years from the onset of CP and 6.7 years from the first P-ESWL procedure. Complete stone clearance was achieved in 73.7% of the patients. At the end of the follow-up period, 70.1% of the patients achieved complete pain remission. Significant pain type conversion and lower VAS scores were observed in the patients after treatment. Quality-of-life scores and body mass indices increased after P-ESWL and ERCP. CONCLUSIONS: P-ESWL and ERCP are effective and minimally invasive treatments for pancreatic stones in patients with painful CP. Most patients achieved complete pain relief, and pain-type conversion was common after treatment. (ClinicalTrials.gov: NCT05916547).
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BACKGROUND: Fungal skin diseases are common skin diseases with a heterogeneous distribution worldwide. OBJECTIVES: This study aimed to analyse the spatiotemporal trends in the burden of fungal skin diseases at global, regional, and national levels from 1990 to 2021. METHODS: Based on the data obtained from the Global Burden of Disease Study (GBD) 2021, we described the incident cases, prevalent cases, number of disability-adjusted life years (DALYs), and corresponding age-standardised rates (ASRs) for fungal skin diseases in 1990 and 2021 by sex, age, socio-demographic index (SDI), 21 GBD regions, and 204 countries and territories. We used Joinpoint regression analysis to assess the temporal trends in burden of fungal skin diseases during 1990 to 2021. Spearman's rank test was used to analyse the relationship between disease burden and potential factors. RESULTS: From 1990 to 2021, the incident cases, prevalent cases, and DALYs for fungal skin diseases worldwide increased by 67.93%, 67.73%, and 66.77%, respectively. Globally, the age-standardised incidence rate (ASIR), age-standardised prevalence rate (ASPR), and age-standardised DALYs rate (ASDR) for fungal skin diseases in 2021 were 21668.40 per 100,000 population (95% UI: 19601.19-23729.17), 7789.55 per 100,000 population (95% UI: 7059.28-8583.54), and 43.39 per 100,000 population (95% UI: 17.79-89.10), respectively. Between 1990 and 2021, the ASIR, ASPR, and ASDR for fungal skin diseases have modestly increased, with AAPC of 11.71% (95% confidence interval [CI]: 11.03%-12.39%), 19.24% (95% CI: 18.12%-20.36%), and 20.25% (95% CI: 19.33%-21.18%), respectively. Males experienced a higher burden of fungal skin diseases than females. The incident cases, prevalent cases, and DALYs for fungal skin diseases were highest at the age of 5-9, while the ASRs were highest among the elderly. At national level, the highest ASRs were observed in Nigeria, Ethiopia, and Mali. Overall, SDI was negatively correlated with the ASRs, whereas Global Land-Ocean Temperature Index (GLOTI) was remarkably positively correlated with the burden of fungal skin diseases. CONCLUSIONS: Between 1990 and 2021, the global burden of fungal skin diseases has increased, causing a high disease burden worldwide, particularly in underdeveloped regions and among vulnerable population such as children and the elderly. With global warming and aging of the population, the burden of fungal skin diseases may continue to increase in the future. Targeted and specific measures should be taken to address these disparities and the ongoing burden of fungal skin diseases.
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Mycoses cutanées , Charge mondiale de morbidité , Santé mondiale , Humains , Mâle , Femelle , Adulte , Mycoses cutanées/épidémiologie , Adulte d'âge moyen , Prévalence , Incidence , Jeune adulte , Santé mondiale/statistiques et données numériques , Adolescent , Sujet âgé , Espérance de vie corrigée de l'incapacité , Enfant d'âge préscolaire , Enfant , Nourrisson , Nouveau-né , Sujet âgé de 80 ans ou plus , Coûts indirects de la maladieRÉSUMÉ
Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.
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Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The "gut-heart" axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5 mg kg-1·d-1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating co-metabolism and regulating the TMAO-inflammation axis.
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As the most abundant messenger RNA (mRNA) modification in mRNA, N 6-methyladenosine (m6A) plays a crucial role in RNA fate, impacting cellular and physiological processes in various tumor types. However, our understanding of the function and role of the m6A methylome in tumor heterogeneity remains limited. Herein, we collected and analyzed m6A methylomes across nine human tissues from 97 m6A sequencing (m6A-seq) and RNA sequencing samples. Our findings demonstrate that m6A exhibits different heterogeneity in most tumor tissues compared to normal tissues, which contributes to the diverse clinical outcomes in different cancer types. We also found that the cancer type-specific m6A level regulated the expression of different cancer-related genes in distinct cancer types. Utilizing a novel and reliable method called "m6A-express", we predicted m6A-regulated genes and revealed that cancer type-specific m6A-regulated genes contributed to the prognosis, tumor origin, and infiltration level of immune cells in diverse patient populations. Furthermore, we identified cell-specific m6A regulators that regulate cancer-specific m6A and constructed a regulatory network. Experimental validation was performed, confirming that the cell-specific m6A regulator CAPRIN1 controls the m6A level of TP53. Overall, our work reveals the clinical relevance of m6A in various tumor tissues and explains how such heterogeneity is established. These results further suggest the potential of m6A for cancer precision medicine for patients with different cancer types.
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Intertrochanteric femur fracture is the most common hip fracture in elderly people, and the academic community has reached a consensus that early surgery is imperative. Proximal femoral nail anti-rotation (PFNA) and InterTan are the preferred internal fixation devices for intertrochanteric femur fractures in elderly individuals due to their advantages, such as a short lever arm, minimal stress shielding, and resistance to rotation. However, PFNA is associated with complications such as nail back-out and helical blade cut-out due to stress concentration. As a new internal fixation device for intertrochanteric femur fractures, the proximal femoral biodegradable nail (PFBN) addresses the issue of nail back-out and offers more stable fracture fixation, a shorter lever arm, and stress distribution compared to PFNA and InterTan. Clinical studies have shown that compared to PFNA, PFBNs lead to faster recovery of hip joint function, shorter non-weight-bearing time, and faster fracture healing. This article provides a literature review of the structural characteristics, biomechanical analysis, and clinical studies of PFBNs, aiming to provide a theoretical basis for the selection of internal fixation devices for the treatment of intertrochanteric femur fractures in elderly patients and to improve the quality of life of patients during the postoperative period.
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BACKGROUND: Indeterminate dendritic cell tumor (IDCT) is a rare tumor of immune cells, and IDCT patients without skin lesions are rarely reported. Therefore, the clinical course in this type of patient is unclear, and further research on the underlying pathological mechanisms and appropriate treatments is needed. CASE SUMMARY: This study describes a female IDCT patient with bile duct lesions. The strong mimicry of IDCT lesions confused doctors, and consequently, this patient, who had no skin lesions, was first diagnosed with cholangiocarcinoma. Then, she presented with persistent abdominal distension without jaundice. Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination. However, no tumor cells or pathogens were found in the three subsequent ascites analyses. It took 2 years to reach the correct diagnosis, which was eventually obtained by performing surgery for biopsy of the patient's abdominal lymph nodes. However, by then, she was already in a cachexic state. Finally, she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases. CONCLUSION: For IDCT patients without skin lesions, early biopsy is the key to obtaining a correct diagnosis. Moreover, the collective management of IDCT patients is important. Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.
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Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.
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Background: Atrial fibrillation (AF) is a common arrhythmia that can result in adverse cardiovascular outcomes but is often difficult to detect. The use of machine learning (ML) algorithms for detecting AF has become increasingly prevalent in recent years. This study aims to systematically evaluate and summarize the overall diagnostic accuracy of the ML algorithms in detecting AF in electrocardiogram (ECG) signals. Methods: The searched databases included PubMed, Web of Science, Embase, and Google Scholar. The selected studies were subjected to a meta-analysis of diagnostic accuracy to synthesize the sensitivity and specificity. Results: A total of 14 studies were included, and the forest plot of the meta-analysis showed that the pooled sensitivity and specificity were 97% (95% confidence interval [CI]: 0.94-0.99) and 97% (95% CI: 0.95-0.99), respectively. Compared to traditional machine learning (TML) algorithms (sensitivity: 91.5%), deep learning (DL) algorithms (sensitivity: 98.1%) showed superior performance. Using multiple datasets and public datasets alone or in combination demonstrated slightly better performance than using a single dataset and proprietary datasets. Conclusions: ML algorithms are effective for detecting AF from ECGs. DL algorithms, particularly those based on convolutional neural networks (CNN), demonstrate superior performance in AF detection compared to TML algorithms. The integration of ML algorithms can help wearable devices diagnose AF earlier.
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OBJECTIVES: Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals. METHODS: We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis. RESULTS: Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD. CONCLUSIONS: This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis.