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

Background: Advances in intensive care have markedly improved survival after severe brain injury, leading to a growing population of patients with prolonged disorders of consciousness (pDOC). Current management of pDOC remains largely supportive, and evidence-based neuromodulatory interventions are limited; moreover, existing guidelines provide insufficiently explicit recommendations regarding mechanisms of action and objective biomarkers of treatment response. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potential noninvasive intervention; however, its modulatory effects on brain function in pDOC are not yet well characterized, and the paucity of integrative mechanistic evidence has constrained its translation into routine clinical practice. Objectives: Within a multimodal assessment framework, this study aims to systematically elucidate the neurobiological mechanisms by which taVNS modulates brain function and autonomic activity in patients with pDOC, and to evaluate its clinical potential to enhance levels of consciousness. Methods: In this randomized controlled trial, 60 patients with vegetative state/minimally conscious state will be enrolled and randomly allocated to a taVNS group, a transcutaneous nonauricular vagus nerve stimulation group (sham), or a control group (n = 20 per group) for a 4-week intervention. The primary outcome will be changes in the Coma Recovery Scale-Revised scores from baseline to weeks 1, 2, and 4 of treatment. Secondary outcomes will include functional brain activity assessed by electroencephalography and functional near-infrared spectroscopy, as well as autonomic modulation indexed by heart rate variability. Functional prognosis will be evaluated using the Glasgow Outcome Scale-Extended at the end of treatment and at a 6-month follow-up. Safety will be assessed by continuous monitoring and documentation of adverse events throughout the study period. Results and discussion: By integrating electroencephalography–functional near-infrared spectroscopy with heart rate variability, this study will characterize the effects of taVNS on functional brain networks and consciousness recovery in pDOC across complementary behavioral, electrophysiological, hemodynamic, and autonomic domains, while interrogating potential sources of clinical and neurobiological heterogeneity. The findings are expected to provide a mechanistic and evidence-based foundation for the mechanism-driven clinical implementation of taVNS and the optimization of stimulation protocols in pDOC. Clinical trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR20250021041, https://itmctr.ccebtcm.org.cn.

Factorial design is an important method for optimizing complex strategies in implementation science. This paper systematically elucidates the origin, types, and core concepts of the factorial design, and then use a brief smoking cessation intervention project as an example to illustrate its specific applications in identifying key factors and testing interactions. Factorial design has the following typical advantages: it can test synergistic and antagonistic effects between factors, provide effect estimates that are broadly valid across the experimental conditions, and offer high statistical efficiency. At the same time, it also has certain limitations, including that its complexity is positively correlated with the number of factors, the need for large sample sizes to detect interactions, the potential for insufficient acceptability of some strategy combinations due to ethical concerns or participant burden, and the complexity of the analytical methods required. In future research, its application should be further optimized by appropriately controlling the number of factors, clearly defining research objectives, and evaluating intervention acceptability, in order to promote the development of precision implementation science.

Objective: To evaluate oral health status and knowledge, attitude and practice (KAP) among third grade primary school students after the implementation of the Comprehensive Intervention Project for Childhood Oral Diseases in Guizhou Province, so as to provide evidence for program optimization. Methods: Using a multistage cluster sampling method, oral examinations and questionnaire surveys were conducted among third grade primary school students in schools covered by the Comprehensive Intervention Project for Childhood Oral Diseases in Guizhou Province (intervention group, n =1 030) and schools not covered by the program (control group， n =1 130) in November 2023. A follow up survey was conducted one year after the project s implementation (December 2024) to evaluate the differences in oral health status and KAP between the two groups. The t-test and χ 2 test were used to compare means and rates, respectively. Results: One year after implementation, the permanent caries prevalence, caries filling ratio, mean dmft/DMFT, and mean simplified debris index in the intervention group were 33.3%, 22.3 %, 3.44±3.10, 0.77±0.56, which were all better than those in the control group (39.8%, 17.3%, 3.89±2.85, and 0.87± 0.63 ) ( χ 2/ t =9.87, 8.78, -2.59, -3.91,all P <0.05). After intervention, the levels of oral health knowledge, attitude and behaviors in the intervention group were better than those in the control group ( Z =7.69, 2.35, 2.10, all P <0.05). Except for the item "fluoride has no protective effect on teeth", the correct response rates of other oral health knowledge items in the intervention group were higher than those in the control group ( χ 2=3.92-163.94, all P <0.05). The reported rates of tooth brushing related behaviors and sugary beverage consumption were higher in the intervention group than in the control group ( χ 2=4.02-11.42，all P <0.05). Conclusions The Comprehensive Intervention Project for Childhood Oral Diseases improves children s oral health status, oral health knowledge, and some oral health behaviors, but has limited effects on some behaviors and oral health attitudes. Future efforts should focus on the factors influencing the transformation of children s oral health attitudes and behaviors, along with strengthening long term follow up evaluations.

Vancomycin is a glycopeptide antibiotic widely used for severe infections caused by gram-positive bacteria. Nevertheless， its clinical application is limited by a narrow therapeutic window and inter-individual differences in pharmacokinetics. Conventional dosing regimens rely on clinical experience and population pharmacokinetic models， which make precise therapy difficult. The emergence of machine learning provides new insights into tackling the above challenges. By integrating multi-dimensional data including demographic characteristics， clinical indicators and combined medications， machine learning can assist individualized medication for patients and improve the capacity for vancomycin dose prediction， in vivo exposure assessment and renal toxicity risk warning. However， the application of machine learning still faces multiple challenges such as poor data quality， weak model generalization ability and insufficient interpretability. Its clinical value needs to be further confirmed by prospective studies and external validation. Future research may consider deep integration of machine learning and population pharmacokinetic models to better support vancomycin individualized medication.

This paper summarizes the experience of Professor TU Jinwen in the staged treatment of oculomotor nerve palsy （ONP） based on the theory of qi collaterals. In the acute onset stage， the key pathogenesis is triggered by wind toxin and disharmony of the qi collaterlas， for which the treatment should prioritize the elimination of pathogenic factors， with therapeutic principles of dispelling wind and eliminating toxin， boosting qi and harmonizing collaterals， using modified Qianzheng Powder （牵正散） plus Buzhong Yiqi Decoction （补中益气汤）. In the remission and recovery stage， the key pathogenesis is stagnation of blood stasis and damage to the qi collaterals， it is recommended to treat the branch， with principles of boosting qi and activating blood， resolving stasis and unblocking collaterals， using the modified Buyang Huanwu Decoction （补阳还五汤）. In the sequela and protracted stage， the key pathogenesis is depletion of the liver， spleen， and kidney with non-nourishment of the qi collaterals； the treatment should focus on addressing the root cause， with principles of fortifying the spleen and boosting qi， tonifying the liver and kidney， using the modified Sijunzi Decoction （四君子汤） combined with Qiju Dihuang Pill （杞菊地黄丸）.

ObjectiveTo explore the effects of "dryness pathogen" on a bronchial asthma rat model from the perspective of the prostaglandin D₂ （PGD₂）/eosinophil （EOS） axis. MethodsForty SD rats were randomly divided into five groups， blank group， asthma group， mild dryness asthma group， moderate dryness asthma group， and severe dryness asthma group， with 8 rats in each group. The asthma model was induced in the asthma group using ovalbumin （OVA）， while the asthma-dryness syndrome groups were modeled using a climate chamber combined with OVA to establish animal models of bronchial asthma with Northwest dryness syndrome. During modeling， general behavioral performance of the rats in each group was observed and recorded， and body weight， water intake， and asthma symptom scores were compared. On day 21 of the modeling， small animal respiratory system testing was used to measure respiratory rate and intermittent respiratory contraction index. Pathological changes in rat lung tissues were observed using HE staining. Giemsa staining was used to observe eosinophil （EOS） infiltration in lung tissues and calculate EOS counts. ELISA was used to detect serum levels of prostaglandin D₂ （PGD₂）， interleukin-5 （IL-5）， and interleukin-4 （IL-4）. Western Blot was used to detect eosinophil peroxidase （EPX） and prostaglandin D₂ receptor （CRTH2） protein levels in rat lung tissues. ResultsCompared to the blank group， the average water intake of rats in all asthma-dryness groups increased （P＜0.01）. The body weight of rats decreased in the moderate and severe asthma-dryness groups on day 14， and in all modelling groups on day 21 （P＜0.05 or P＜0.01）. Across all model groups， the asthma symptom score， respiratory rate， intermittent respiratory contraction index， EOS count in lung tissue， serum levels of PGD₂， IL-5， and IL-4， as well as the relative protein expression levels of EPX and CRTH2 in lung tissue all significantly increased （P＜0.01）. Compared to the asthma group， the water intake of rats in the mild， moderate， and severe asthma-dryness groups increased （P＜0.01）. On day 21 of the experiment， the body weight of rats in the moderate and severe asthma-dryness groups decreased （P＜0.05）， and the respiratory rate of rats in all asthma-dryness groups increased， as well as the serum levels of PGD₂， IL-5， and IL-4， and the relative protein expression levels of EPX and CRTH2 in lung tissues （P＜0.05 or P＜0.01）. Furthermore， in the moderate and severe asthma-dryness groups， the asthma symptom scores and intermittent respiratory contraction indices were elevated， and the EOS counts in lung tissue increased （P＜0.05 or P＜0.01）. Compared to the mild asthma-dryness group， serum levels of PGD₂， IL-5， and IL-4 in the severe asthma-dryness group increased， as well as the relative protein expression levels of EPX and CRTH2 in lung tissue （P＜0.05 or P＜0.01）. Pathological observation showed that rats in all asthma-dryness syndrome groups exhibited increased inflammatory infiltration in the lung tissue， alveolar wall thickening， luminal narrowing， pulmonary interstitial congestion， and aggravated viscous secretions. These pathological manifestations worsened as the degree of dryness increased. ConclusionThe "dryness pathogenic factor" can exacerbate bronchial asthma symptoms and lung tissue pathological damage through the PGD₂/EOS axis， and the damage progressively worsens with the increasing severity of the dryness pathogen.

AIM:To explore the effectiveness of predictive models based on quantitative characteristics of multimodal fundus images in assessing the risk of progression of non-proliferative diabetic retinopathy(NPDR).METHODS:A single-center retrospective cohort study was conducted. Patients diagnosed with moderate to severe NPDR between January 2021 and December 2023 in Wuhan Ninth Hospital were selected. Baseline color fundus photography(CFP), optical coherence tomography(OCT), and fundus autofluorescence(FAF)images were collected. Microaneurysm count, hard exudate area, central retinal thickness, retinal nerve fiber layer thickness, and total area of hyperautofluorescent spots were extracted and quantified. All patients were followed up regularly. The primary endpoint was the progression to treatment-requiring proliferative diabetic retinopathy(PDR)or clinically significant diabetic macular edema(DME)during the follow-up period. According to the occurrence of endpoint events during follow-up, the patients were divided into the progression group and the non-progression group. Combined with clinical significance and inter-group comparison results, candidate quantitative imaging parameters were included in the multivariate logistic regression analysis to construct a prediction model. The model was visualized using a Nomogram. The discriminative ability and calibration degree of the model were evaluated via receiver operating characteristic(ROC)curves and calibration curves.RESULTS:A total of 300 patients(300 eyes)completed follow-up, with 93 in the progression group, including 47 males and 46 females, with an average age of 59.02±8.21 y. There were 207 cases in the non-progression group, including 105 males and 102 females, with an average age of 58.01±8.10 y. Multivariate logistic regression showed that the total area of FAF hyperautofluorescent spots(OR=1.580, 95%CI: 1.061-1.718, P=0.002),OCT retinal nerve fiber layer thickness(OR=1.520, 95%CI: 1.307-6.212, P=0.013), and CFP microaneurysm count(OR=1.459, 95%CI: 1.089-2.095, P=0.015)were risk factors for DR progression. The AUC of the Nomogram for predicting progression risk during the follow-up period was 0.889(95%CI: 0.826-0.952), and the calibration curve showed good consistency between predicted probability and actual risk.CONCLUSION: The prediction model integrating quantitative imaging features of CFP, OCT and FAF can effectively identify NPDR patients with high progression risk and exhibits good predictive efficacy, which can serve as a quantitative tool for individualized clinical risk management.

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*