Development and status quo of digestive endoscopy in China: An analysis based on the national census in 2013 and 2020.

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China. Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China. Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita (P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers. Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better.

Clinical characteristics and molecular mechanisms underlying bladder cancer in individuals with spinal cord injury: a systematic review.

BACKGROUND: Patients with spinal cord injury have a relatively high risk for bladder cancer and often complicated with bladder cancer in advanced stages, and the degree of aggressiveness of malignancy is high. Most of the literature is based on disease clinical features while, our study reviews the clinical characteristics and molecular mechanisms of spinal cord injury patients with bladder cancer, so that it might help clinicians better recognize and manage these patients. METHOD: We searched PubMed, Web of Science and Embase, using retrieval type like ("Neurogenic Lower Urinary Tract Dysfunction" OR "Spinal cord injury" OR "Spinal Cord Trauma") AND ("bladder cancer" OR "bladder neoplasm" OR "bladder carcinoma" OR "Urinary Bladder Neoplasms" OR "Bladder Tumor"). In Web of Science, the retrieval type was searched as "Topic", and in PubMed and Embase, as "All Field". The methodological quality of eligible studies and their risk of bias were assessed using the Newcastle-Ottawa scale. This article is registered in PROSPERO with the CBD number: CRD42024508514. RESULT: In WOS, we searched 219 related papers, in PubMed, 122 and in Embase, 363. Thus, a total of 254 articles were included after passing the screening, within a time range between 1960 and 2023. A comprehensive analysis of the data showed that the mortality and incidence rates of bladder cancer in spinal cord injury patients were higher than that of the general population, and the most frequent pathological type was squamous cell carcinoma. In parallel to long-term urinary tract infection and indwelling catheterization, the role of molecules such as NO, MiR 1949 and Rb 1. was found to be crucial pathogenetically. CONCLUSION: This review highlights the risk of bladder cancer in SCI patients, comprehensively addressing the clinical characteristics and related molecular mechanisms. However, given that there are few studies on the molecular mechanisms of bladder cancer in spinal cord injury, further research is needed to expand the understanding of the disease.

Effects of glycopyrrolate and atropine for oral secretions and perioperative hemodynamics in children undergoing tonsillectomy and adenoidectomy: a prospective, single-center, randomized, double-blind, controlled trial.

Introduction: Glycopyrrolate is commonly researched as a preoperative medication or in conjunction with cholinesterase inhibitors to counteract the lingering muscarinic effects of non-depolarizing muscarinic agents. However, studies have yielded inconsistent results regarding the superiority of glycopyrrolate over other anti-cholinergic drugs, such as atropine, particularly its effect on heart rate, blood pressure (BP), and glandular secretions. This study aimed to evaluate the differences in perioperative oral secretions, hemodynamics, and recovery quality with glycopyrrolate versus those with atropine before anesthesia induction in children undergoing tonsillectomy and adenoidectomy. Methods: In this prospective, single-center, randomized, double-blind, controlled trial, a total of 103 children were randomly assigned to group A (n = 51, glycopyrrolate 0.005 mg/kg) or B (n = 52, atropine 0.01 mg/kg). The follow-up anesthetic induction and maintenance protocols were the same in both groups. Vital signs, duration of surgery, extubation time, degree of wetness around the vocal cords during tracheal intubation, weight of oral secretions, and perioperative complications were recorded. Results: No significant differences were observed in the degree of wetness around the vocal cords during tracheal intubation, as well as in the weight of oral secretions, duration of surgery, or extubation time, between the two groups. The intraoperative and postoperative heart rates were lower in group A than in group B (110.18 ± 10.58 vs. 114.94 ± 11.14, p = 0.028; 96.96 ± 10.81 vs. 103.38 ± 10.09, p = 0.002). The differences observed in the intraoperative and preoperative heart rates were lower in group A than in group B (23.84 ± 9.62 vs. 29.65 ± 8.75, p = 0.002). The differences observed in the postoperative and preoperative heart rates were lower in group A than in group B (10.63 ± 9.97 vs. 18.09 ± 9.39, p = 0.000). Conclusion: Glycopyrrolate showed a smoother change in heart rate than atropine during and after tonsillectomy and adenoidectomy, with no effect on BP or recovery quality, and did not increase oral secretions. The findings indicate that glycopyrrolate can serve as an alternative to atropine to prevent secretions in anesthesia induction for tonsillectomy and adenoidectomy in children. Trial registration: This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200063578; Date of Registration: 12/09/2022).

Targeting tumor suppressor p53 for organ fibrosis therapy.

Fibrosis is a reparative and progressive process characterized by abnormal extracellular matrix deposition, contributing to organ dysfunction in chronic diseases. The tumor suppressor p53 (p53), known for its regulatory roles in cell proliferation, apoptosis, aging, and metabolism across diverse tissues, appears to play a pivotal role in aggravating biological processes such as epithelial-mesenchymal transition (EMT), cell apoptosis, and cell senescence. These processes are closely intertwined with the pathogenesis of fibrotic disease. In this review, we briefly introduce the background and specific mechanism of p53, investigate the pathogenesis of fibrosis, and further discuss p53's relationship and role in fibrosis affecting the kidney, liver, lung, and heart. In summary, targeting p53 represents a promising and innovative therapeutic approach for the prevention and treatment of organ fibrosis.

Discovery of the Clinical Candidate Sonrotoclax (BGB-11417), a Highly Potent and Selective Inhibitor for Both WT and G101V Mutant Bcl-2.

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax's limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment.

Magnon-Skyrmion Hybrid Quantum Systems: Tailoring Interactions via Magnons.

Coherent and dissipative interactions between different quantum systems are essential for the construction of hybrid quantum systems and the investigation of novel quantum phenomena. Here, we propose and analyze a magnon-skyrmion hybrid quantum system, consisting of a micromagnet and nearby magnetic skyrmions. We predict a strong-coupling mechanism between the magnonic mode of the micromagnet and the quantized helicity degree of freedom of the skyrmion. We show that with this hybrid setup it is possible to induce magnon-mediated nonreciprocal interactions and responses between distant skyrmion qubits or between skyrmion qubits and other quantum systems like superconducting qubits. This work provides a quantum platform for the investigation of diverse quantum effects and quantum information processing with magnetic microstructures.

Gut Microbiota Analysis in Silkworms (Bombyx mori) Provides Insights into Identifying Key Bacterials for Inclusion in Artificial Diet Formulations.

The gut microbiome significantly influences the health and productivity of silkworms (Bombyx mori), the cornerstone of sericulture. With the increasing use of cost-effective artificial diets in sericulture, it is crucial to understand how these diets impact the silkworm gut microbiomes. Here we employed 16S rRNA sequencing to delineate the impact of three distinct dietary regimens on the silkworm gut microbiomes: exclusive mulberry leaf diet (SY), exclusive artificial feed diet (SL), and a sequential transition from artificial feed to mulberry leaves (ZS). Our results unveiled stark differences in microbial diversity across the groups, with the ZS group displaying an intermediary complexity. LefSe and random forest analyses identified Methylobacteriaceae, Microbacterium, and Rhodococcus as significantly enriched in the ZS group, suggesting their potential to facilitate silkworms' adaptation to dietary transitions. Functional profiling revealed differential pathway regulation, indicating a metabolic reconfiguration in response to dietary modulations. Notably, the enrichment of Lactobacillus and Weissella in both the SL and ZS groups highlights their potential as probiotics in artificial diets. Our findings provide insights into the diet adaptation mechanisms of silkworm gut microbiota, paving the way for harnessing the intestinal bacteria to enhance silkworm health and silk production through targeted microbial interventions in sericulture practices.

Predicting the new psychoactive substance activity of antitussives and evaluating their ecotoxicity to fish.

The misuse of antitussives preparations is a continuing problem in the world, and imply that they might have potential new psychoactive substances (NPS) activity. However, few study focus on their ecological toxicity towards fish. In the present study, the machine learning (ML) methods gcForest and random forest (RF) were employed to predict NPS activity in 30 antitussives. The potential toxic target, mode of action (MOA), acute toxicity and chronic toxicity to fish were further investigated. The results showed that both gcForest and RF achieved optimal performance when utilizing combined features of molecular fingerprint (MF) and molecular descriptor (MD), with area under the curve (AUC) = 0.99, accuracy >0.94 and f1 score > 0.94, and were applied to screen the NPS activity in antitussives. A total of 15 antitussives exhibited potential NPS activity, including frequently-used substances like codeine and dextromethorphan. The binding affinity of these antitussives with zebrafish dopamine transporter (zDAT) was high, and even surpassing that of some traditional narcotics and NPS. Some antitussives formed hydrogen bonds or salt bridges with aspartate (Asp) 95, tyrosine (Tyr) 171 of zDAT. For the ecotoxicity, the MOA of these 15 antitussives in fish was predicted as narcosis. The prenoxdiazin, pholcodine, codeine, dextromethorphan and dextrorphan exhibited very toxic/toxic to fish. It was necessary to pay close attention to the ecotoxicity of these antitussives. In this study, the integration of ML, molecular docking and ECOSAR approaches are powerful tools for understanding the toxicity profiles and ecological hazards posed by new pollutants.

The significance of single-cell transcriptome analysis in epididymis research.

As a crucial component of the male reproductive system, the epididymis plays multiple roles, including sperm storage and secretion of nutritive fluids for sperm development and maturation. The acquisition of fertilization capacity by sperm occurs during their transport through the epididymis. Compared with the testis, little has been realized about the importance of the epididymis. However, with the development of molecular biology and single-cell sequencing technology, the importance of the epididymis for male fertility should be reconsidered. Recent studies have revealed that different regions of the epididymis exhibit distinct functions and cell type compositions, which are likely determined by variations in gene expression patterns. In this research, we primarily focused on elucidating the cellular composition and region-specific gene expression patterns within different segments of the epididymis and provided detailed insights into epididymal function in male fertility.

Deep-targeted gene sequencing reveals ARID1A mutation as an important driver of glioblastoma.

AIMS: To investigate the key factors influencing glioma progression and the emergence of treatment resistance by examining the intrinsic connection between mutations in DNA damage and repair-related genes and the development of chemoresistance in gliomas. METHODS: We conducted a comprehensive analysis of deep-targeted gene sequencing data from 228 glioma samples. This involved identifying differentially mutated genes across various glioma grades, assessing their functions, and employing I-TASSER for homology modeling. We elucidated the functional changes induced by high-frequency site mutations in these genes and investigated their impact on glioma progression. RESULTS: The analysis of sequencing mutation results of deep targeted genes in integration revealed that ARID1A gene mutation occurs frequently in glioblastoma and alteration of ARID1A could affect the tolerance of glioma cells to temozolomide treatment. The deletion of proline at position 16 in the ARID1A protein affected the stability of binding of the SWI/SNF core subunit BRG1, which in turn affected the stability of the SWI/SNF complex and led to altered histone modifications in the CDKN1A promoter region, thereby affecting the biological activity of glioma cells, as inferred from modeling and protein interaction analysis. CONCLUSION: The ARID1A gene is a critical predictive biomarker for glioma. Mutations at the ARID1A locus alter the stability of the SWI/SNF complex, leading to changes in transcriptional regulation in glioma cells. This contributes to an increased malignant phenotype of GBM and plays a pivotal role in mediating chemoresistance.

Genetically determined type 1 diabetes mellitus and risk of osteoporosis.

BACKGROUND: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. METHODS: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. RESULTS: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012-1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005-1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975-1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985-1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. CONCLUSIONS: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.

Association between physical activity and risk of gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND: Lifestyle plays an important role in preventing and managing gastroesophageal reflux disease (GERD). In response to the conflicting results in previous studies, we performed a systematic review and meta-analysis to investigate this association. METHODS: Relevant studies published until January 2023 were retrieved from 6 databases, and the prevalence of symptomatic gastroesophageal reflux (GER) or GERD was determined from the original studies. A random effects model was employed to meta-analyze the association by computing the pooled relative risk (RR) with 95% confidence intervals (95%CIs). Furthermore, subgroup and dose-response analyses were performed to explore subgroup differences and the association between cumulative physical activity (PA) time and GERD. RESULTS: This meta-analysis included 33 studies comprising 242,850 participants. A significant negative association was observed between PA and the prevalence of symptomatic GER (RR = 0.74, 95%CI: 0.66-0.83; p < 0.01) or GERD (RR = 0.80, 95%CI: 0.76-0.84; p < 0.01), suggesting that engaging in PA might confer a protective benefit against GERD. Subgroup analyses consistently indicated the presence of this association across nearly all subgroups, particularly among the older individuals (RR<40 years:RR≥40 years = 0.85:0.69, p < 0.01) and smokers (RRsmoker:RRnon-smoker = 0.67:0.82, p = 0.03). Furthermore, a dose-response analysis revealed that individuals who engaged in 150 min of PA per week had a 72.09% lower risk of developing GERD. CONCLUSION: Maintaining high levels of PA decreased the risk of GERD, particularly among older adults and smokers. Meeting the recommended PA level of 150 min per week may significantly decrease the prevalence of GERD.

Atlas and source of the microplastics of male reproductive system in human and mice.

Regarding the impact of microplastics (MPs) on the male reproductive system, previous studies have identified a variety of MPs in both human semen and testicular samples. These studies have put forward the hypothesis that small particles can enter the semen through the epididymis and seminal vesicles. Here, we performed qualitative and quantitative analyses of MPs in human testis, semen, and epididymis samples, as well as in testis, epididymis, seminal vesicle, and prostate samples from mice via pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The goal of this approach was to comprehensively characterize the distribution of MPs within the male reproductive system. Additionally, we aimed to evaluate potential sources of MPs identified in semen, as well as to identify possible sources of overall MP exposure. Our results highlighted a general atlas of MPs in the male reproductive system and suggested that MPs in semen may originate from the epididymis, seminal vesicles, and prostate. An exposure questionnaire, coupled with the characteristics of the MPs detected in the male reproductive system, revealed that high urbanization, home-cooked meals, and using scrub cleansers were important sources of MP exposure in men. These findings may provide novel insights into alleviating the exposure of men to MPs.

Respective evolution of soil and biochar on competitive adsorption mechanisms for Cd(II), Ni(II), and Cu(II) after 2-year natural ageing.

To reveal the respective evolution of soil and biochar on competitive heavy metal adsorption mechanisms after natural ageing, three soils and two biochars were tested in this study. The soil-biochar interlayer samples were buried in the field for 0.5, 1, and 2 years, for which competitive adsorption characteristics and mechanisms of soils and biochars in four systems (Cd, Cd+Ni, Cd+Cu, and Cd+Ni+Cu) were investigated. Results showed that physicochemical properties, adsorption capacity and mechanisms of soils and biochars all changed the most in the first 0.5 years. The properties and adsorption capacity of biochars gradually weakened with the ageing time, meanwhile, those of soils gradually enhanced. After co-ageing with acidic soil for 0.5 years, the Cd(II) adsorption capacity of modified biochar decreased by 86.59% in the ternary system; meanwhile, that of acidic soil increased by 65.52%. The contributions of mineral mechanisms decreased significantly, while non-mineral mechanisms were slightly affected by ageing. This study highlighted that when using biochar to remediate heavy metal-contaminated soils, biochar should be applied at least half a year in advance before planting crops so that biochar can fully contact and react with the soil.

A systematic approach for authentication of medicinal Patrinia species using an integration of morphological, chemical and molecular methods.

Four common Patrinia species, including P. heterophylla, P. monandra, P. scabiosifolia and P. villosa, have been documented as herbal medicines with various clinical applications, such as anti-cancer, anti-diarrhea and sedative. However, the authentication of medicinal Patrinia species poses a problem, particularly with the processed herbal materials. This study aimed to systematically authenticate the four medicinal Patrinia species in the market using morphological and chemical characterization, as well as DNA markers. We found the species identity authenticated by traditional morphologies were in good agreement with both chemical and molecular results. The four species showed species-specific patterns in chromatographic profiles with distinct chemical markers. We also revealed the power of complete chloroplast genomes in species authentication. The sequences of targeted loci, namely atpB, petA, rpl2-rpl23 and psaI-ycf4, contained informative nucleotides for the species differentiation. Our results also facilitate authentication of medicinal Patrinia species using new DNA barcoding markers. To the best of our knowledge, this is the first report on the application of morphology, chemical fingerprinting, complete chloroplast genomes and species-specific Insertion-Deletions (InDels) in differentiating Patrinia species. This study reported on the power of a systematic, multidisciplinary approach in authenticating medicinal Patrinia species.

Phosphorylation of TG-interacting factor 1 at carboxyl-terminal sites in response to insulin regulates adipocyte differentiation.

TG-interacting factor 1 (TGIF1) contributes to the differentiation of murine white preadipocyte and human adipose tissue-derived stem cells; however, its regulation is not well elucidated. Insulin is a component of the adipogenic cocktail that induces ERK signaling. TGIF1 phosphorylation and sustained stability in response to insulin were reduced through the use of specific MEK inhibitor U0126. Mutagenesis at T235 or T239 residue of TGIF1 in preadipocytes led to dephosphorylation of TGIF1. The reduced TGIF1 stability resulted in an increase in p27kip1 expression, a decrease in phosphorylated Rb expression and cellular proliferation, and a reduced accumulation of lipids compared to the TGIF1-overexpressed cells. These findings highlight that insulin/ERK-driven phosphorylation of the T235 or T239 residue at TGIF1 is crucial for adipocyte differentiation.

Liquid biopsy of oesophageal squamous cell carcinoma: implications in diagnosis, prognosis, and treatment monitoring.

Oesophageal squamous cell carcinoma (ESCC) is a common malignant tumour of the gastrointestinal tract. Early detection and access to appropriate treatment are crucial for the long-term survival of patients. However, limited diagnostic and monitoring methods are available for identifying early stage ESCC. Endoscopic screening and surgical resection are commonly used to diagnose and treat early ESCC. However, these methods have disadvantages, such as high recurrence, lethality, and mortality rates. Therefore, methods to improve early diagnosis of ESCC and reduce its mortality rate are urgently required. In 1961, Gary et al. proposed a novel liquid biopsy approach for clinical diagnosis. This involved examining exosomes, circulating tumour cells, circulating free DNA, and circulating free RNA in body fluids. The ability of liquid biopsy to obtain samples repeatedly, wide detection range, and fast detection speed make it a feasible option for non-invasive tumour detection. In clinical practice, liquid biopsy technology has gained popularity for early screening, diagnosis, treatment efficacy monitoring, and prognosis assessment. Thus, this is a highly promising examination method. However, there have been no comprehensive reviews on the four factors of liquid biopsy in the context of ESCC. This review aimed to analyse the progress of liquid biopsy research for ESCC, including its classification, components, and potential future applications.

Regulating ion affinity and dehydration of metal-organic framework sub-nanochannels for high-precision ion separation.

Membrane consisting of ordered sub-nanochannels has been pursued in ion separation technology to achieve applications including desalination, environment management, and energy conversion. However, high-precision ion separation has not yet been achieved owing to the lack of deep understanding of ion transport mechanism in confined environments. Biological ion channels can conduct ions with ultrahigh permeability and selectivity, which is inseparable from the important role of channel size and "ion-channel" interaction. Here, inspired by the biological systems, we report the high-precision separation of monovalent and divalent cations in functionalized metal-organic framework (MOF) membranes (UiO-66-(X)2, X = NH2, SH, OH and OCH3). We find that the functional group (X) and size of the MOF sub-nanochannel synergistically regulate the ion binding affinity and dehydration process, which is the key in enlarging the transport activation energy difference between target and interference ions to improve the separation performance. The K+/Mg2+ selectivity of the UiO-66-(OCH3)2 membrane reaches as high as 1567.8. This work provides a gateway to the understanding of ion transport mechanism and development of high-precision ion separation membranes.