Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Objective: To analyze the association between each regional fat mass and total body bone mineral density (BMD) in children and adolescents aged 7-17 years in Beijing, so as to provide theoretical basis and practical guidance for implementing interventions. Methods: From September to December 2020, a stratified cluster random sampling method was used to select 1 423 children and adolescents aged 7-17 years in Tongzhou District, Beijing. Dual energy X-ray absorptiometry (DXA) was employed to measure regional body composition and total body BMD. Multiple linear regression was used to analyze the association between regional fat mass and total body BMD. Results: The median (interquartile range) fat mass values for total body, upper limbs, abdomen, hips, and thighs were 13.51(8.84, 19.21), 1.59(1.08, 2.23), 0.73(0.39, 1.29), 2.32(1.46, 3.26), 5.29(3.59, 7.21)kg, respectively. After adjusting for covariates, the results of multiple linear regression analysis showed that total body fat mass (β=0.010), abdominal fat mass (β=-0.100), and hip fat mass (β=0.104) were significant associations with total body BMD (all P<0.01). Sexstratified analysis revealed that in boys, total body fat mass (β=0.008) and hip fat mass (β=0.058) were positively associated with BMD, while thigh fat mass (β=-0.038) showed a negative association with total body BMD (all P<0.05). In girls, total body fat mass (β=0.013), hip fat mass (β=0.163), and thigh fat mass (β=0.023) were positively associated with total body BMD, whereas abdominal fat mass (β=-0.196) showed a negative association with total body BMD (all P<0.05). Among children and adolescents with body fat percentage below the standard range, within the standard range and above the standard range, total body fat masses were positively associated with total body BMD (β=0.021, 0.016, 0.015); among children and adolescents with body fat percentage within the standard range while upper limb (β=-0.042), abdominal (β=-0.067), and thigh fat mass (β=-0.018) showed negative associations with total body BMD, and hip fat mass demonstrated a positive association with total body BMD (β=0.082) (all P<0.05). Conclusion Regional fat distribution is associated with total body BMD in children and adolescents, with the nature of these associations varying by sex and body fat percentage.

This article summarized Professor TU Jinwen's experience in treatment of intracranial atherosclerotic stenosis （ICAS） with principles of supplementing deficiency， resolving toxins and unblocking Collaterals. He believes that toxin damaging brain collaterals is the core pathogenesis of ICAS， and thereafter proposed supplementing deficiency， resolving toxins， and unblocking collaterals be the basic treatment method. The emptiness of brain collaterals is the source of the disease. For cases where there is spleen kidney depletion and insufficiency of original qi， the modified Sijunzi Decoction and Liuwei Dihuang Pills （四君子汤合六味地黄丸） could be used to fortify the spleen and tonify the kidneys to enrich the collaterals. The accumulation of turbidity stasis toxin in brain collaterals is essential components of the pathogenesis. For cases where turbidity and stasis combine together， inducing toxins and obstructing the colla-terals， the modified Taohong Siwu Decoction and Erchen Decoction （桃红四物汤合二陈汤） could be used to eliminate toxins and dispel knots to unblock the collaterals. Yin toxins obstructing the latent collaterals represent the gradual progression of pathogenic factors. For cases where turbid stasis transform into cold and yin toxins hide in the collaterals， the modified Buyang Huanwu Decoction and Ditan Decoction （补阳还五汤合涤痰汤） could be used to remove the toxin， warm and activate the collaterals. Heat toxins damaging the collaterals signify aggravated changes in disease. For cases where turbid stasis transforms into heat and toxins injure the brain collaterals， the modified Dachaihu Decoction and Huanglian Jiedu Decoction （大柴胡汤合黄连解毒汤） could be used to cool blood and dredge the fu viscera to clear collaterals.

Objective To evaluate the current radiation doses in pediatric non-cardiac interventional procedures, and analyze the associated clinical factors, and to provide data references for reducing pediatric radiation exposure. Methods We conducted a retrospective analysis of the radiation doses of children who had undergone non-cardiac interventional procedures at the interventional department of a tertiary pediatric hospital in Jinan from January 2022 to October 2024. The collected data included basic demographic information, surgical date, anatomical site, disease type, and radiation dose parameters (cumulative fluoroscopy time, cumulative dose area product in cine mode, cumulative air kerma, and the number of images acquired). The Kruskal-Wallis H test was used for comparative analysis between groups (P < 0.05 was considered statistically significant). Results Among the 475 included children, 99 cases (20.8%) had infantile hemangioma (median P_ka, 0.136 Gy·cm²; median K_a,r, 0.38 mGy), 235 cases (49.5%) had venous malformation (median P_ka, 9.82 Gy·cm²; median K_a,r, 40.99 mGy), 75 cases (15.8%) had lymphatic malformation (median P_ka, 0.06 Gy·cm²; median K_a,r, 0.18 mGy), 32 cases (6.7%) had retinoblastoma (median P_ka, 6.58 Gy·cm²; median K_a,r, 52.34 mGy), 12 cases (2.5%) had arteriovenous malformation (median P_ka, 42.3 Gy·cm²; median K_a,r, 162.87 mGy), and 22 cases (4.6%) had other vascular malformations (median P_ka, 21.7 Gy·cm²; median K_a,r, 89.1 mGy). There were significant differences between children with different disease types in the cumulative fluoroscopy time, cumulative dose area product in cine mode, cumulative air kerma at the patient entrance reference point, and the number of images acquired during non-cardiac interventional procedures (all P < 0.01). Conclusion This study presented the types and proportions of pediatric non-cardiac interventional procedures, evaluated the radiation dose levels of different surgical types, and analyzed the effects of weight and anatomical site on radiation exposure, which can be useful for preliminary assessment of radiation doses in pediatric non-cardiac interventional procedures.

BACKGROUND: China has made significant progress in medical accessibility and quality over the past decades, and quality improvements in gastroenterology and digestive endoscopy have been consistent. The study aimed to describe the status quo of gastroenterology and digestive endoscopy in the Chinese mainland based on the data from the National Clinical Improvement System (NCIS) and the Hospital Quality Monitoring System (HQMS). METHODS: Data were extracted from the NCIS and the HQMS. Data analysis included general information from the Department of Gastroenterology and Endoscopy centers, management of inpatients and outpatients, and annual volume and quality indicators of digestive endoscopy. Acute pancreatitis, gastrointestinal bleeding, inflammatory bowel disease, and cirrhosis were identified as priority diseases and were subjected to detailed analysis. RESULTS: Data from 4620 and 7074 hospitals were extracted from the NCIS and HQMS, respectively. In 2023, 9.6 gastroenterologists, 6.7 endoscopists, and 37.3 gastroenterology beds per hospital nationwide were observed, achieving 19,252.4 outpatient visits, 1615.2 hospitalizations (97.0 for acute pancreatitis, 146.1 for gastrointestinal bleeding, 40.2 for inflammatory bowel disease, and 111.4 for cirrhosis), and 9432.7 digestive endoscopic procedures per hospital. Overall, the quality of practice improved significantly. The proportion of early cancer among gastrointestinal cancers increased from 11.1% in 2015 to 23.4% in 2023, and the adenoma detection rate during colonoscopy increased from 19.3% in 2019 to 26.9% in 2023. Regarding priority diseases, hospitalizations increased, and 31-day unplanned readmission rates decreased between 2019 and 2023. The median hospitalization costs and median proportion of medication costs decreased for acute pancreatitis, gastrointestinal bleeding, and cirrhosis. However, it increased for inflammatory bowel disease. CONCLUSION This report evaluates the status quo and development of gastroenterology and digestive endoscopy in the Chinese mainland, providing guidance for future quality improvements.
Humans ; China ; Gastroenterology/statistics & numerical data* ; Gastrointestinal Hemorrhage ; Endoscopy, Gastrointestinal/statistics & numerical data* ; Endoscopy, Digestive System/statistics & numerical data*

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*