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

Persistent left superior vena cava is a rare venous variant that is often combined with cardiovascular malformations. In thoracic surgery, especially mediastinal tumor resection, neglect of this variant may make the surgery difficult and risky, and careful preoperative imaging interpretation and adequate preoperative evaluation play an important role in the perioperative safety of the patient. In this paper, we reported a case of a 17-year-old female patient with a persistent left superior vena cava combined with mediastinal tumors. She was successfully discharged 5 days after thoracoscopic surgery, and after 3 years of postoperative follow-up, no tumor recurrence was observed.

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

The online and offline hybrid teaching model of evidence-based medicine (EBM) is currently in the stage of development. Previous teaching focused on the teaching process in the classroom, and did not organically combine all the course contents before, during, and after class. The BOPPPS model can be used to establish coherence and integrity in the EBM teaching process. Considering the discipline characteristics and teaching objectives of EBM, this study initially explored and designed a BOPPPS-based online and offline hybrid teaching model. Taking the "diagnostic evidence" module as an example, the teaching implementation details were introduced. A pre-designed questionnaire was used to conduct baseline survey and follow-up survey on students before and after class to evaluate the teaching model and effect. The surveys showed that half of the students (77/154) preferred the new online and offline hybrid teaching model of EBM. The students found that all aspects of BOPPPS teaching were generally acceptable and satisfactory. Compared with before teaching, the students' proficiency in EBM was significantly improved after the teaching ( P<0.001), particularly in their ability to retrieve literature and evaluate the quality of evidence, which is of great significance for expanding their knowledge and clinical thinking.

Objective:This study aims to explore the temporal trend of Low Anterior Resection Syndrome (LARS) and its symptoms after laparoscopic anterior resection for rectal cancer.Methods:A retrospective cohort study design was employed. The study included primary rectal (adenocarcinoma) cancer patients who underwent laparoscopic anterior resection at Tongji Hospital, Huazhong University of Science and Technology, between January 1, 2010, and December 31, 2020. Complete medical records and follow-up data at 3, 6, 9, 12, and 18 months postoperatively were available for all patients. A total of 1454 patients were included, of whom 1094 (75.2%) were aged ≤65 years, and 597 (41.1%) were females. Among them, 1040 cases (71.5%) had an anastomosis-to-anus distance of 0-5cm, and 86 cases (5.9%) received neoadjuvant treatment. All patients completed the Chinese version of the LARS questionnaire and their LARS occurrence and specific symptom information were recorded at 3, 6, 9, 12, and 18 months postoperatively. Considering past literature and clinical experience, further subgroup analyses were performed to explore the potential impact factors on severe LARS, including anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma.Results:The occurrence rates of LARS at 3, 6, 9, 12, and 18 months postoperatively were 78.5% (1142/1454), 71.4% (1038/1454), 55.0% (799/1454), 45.7% (664/1454), and 45.7% (664/1454), respectively (χ 2=546.180 , P<0.001). No statistically significant difference was observed between the 12-month and 18-month time points ( P>0.05). When compared with the symptoms at 3 months, the occurrence rates of gas incontinence [1.7% (24/1454) vs. 33.9% (493/1454)], liquid stool incontinence [3.9% (56/1454) vs. 41.9% (609/1454)], increased stool frequency [79.6% (1158/1454) vs. 95.9% (1395/1454)], stool clustering [74.3% (1081/1454) vs. 92.9% (1351/1454)], and stool urgency [46.5% (676/1454) vs. 78.7% (1144/1454)] in the LARS symptom spectrum were significantly alleviated at 12 months (all P<0.05) and remained stable beyond 12 months (all P>0.05). With the extension of postoperative time, the incidence rates of severe LARS exhibited a decreasing trend in different subgroups, of anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma, and reached stability at 12 months postoperatively (all P>0.05). Conclusion:LARS and its specific symptom profile showed a trend of gradual improvement over time up to 1 year postoperatively, and stabilized after more than 1 year. Increased stool frequency and stool clustering are the most common features of abnormal bowel dys function, which improve slowly after surgery.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Objective:This study aims to explore the temporal trend of Low Anterior Resection Syndrome (LARS) and its symptoms after laparoscopic anterior resection for rectal cancer.Methods:A retrospective cohort study design was employed. The study included primary rectal (adenocarcinoma) cancer patients who underwent laparoscopic anterior resection at Tongji Hospital, Huazhong University of Science and Technology, between January 1, 2010, and December 31, 2020. Complete medical records and follow-up data at 3, 6, 9, 12, and 18 months postoperatively were available for all patients. A total of 1454 patients were included, of whom 1094 (75.2%) were aged ≤65 years, and 597 (41.1%) were females. Among them, 1040 cases (71.5%) had an anastomosis-to-anus distance of 0-5cm, and 86 cases (5.9%) received neoadjuvant treatment. All patients completed the Chinese version of the LARS questionnaire and their LARS occurrence and specific symptom information were recorded at 3, 6, 9, 12, and 18 months postoperatively. Considering past literature and clinical experience, further subgroup analyses were performed to explore the potential impact factors on severe LARS, including anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma.Results:The occurrence rates of LARS at 3, 6, 9, 12, and 18 months postoperatively were 78.5% (1142/1454), 71.4% (1038/1454), 55.0% (799/1454), 45.7% (664/1454), and 45.7% (664/1454), respectively (χ 2=546.180 , P<0.001). No statistically significant difference was observed between the 12-month and 18-month time points ( P>0.05). When compared with the symptoms at 3 months, the occurrence rates of gas incontinence [1.7% (24/1454) vs. 33.9% (493/1454)], liquid stool incontinence [3.9% (56/1454) vs. 41.9% (609/1454)], increased stool frequency [79.6% (1158/1454) vs. 95.9% (1395/1454)], stool clustering [74.3% (1081/1454) vs. 92.9% (1351/1454)], and stool urgency [46.5% (676/1454) vs. 78.7% (1144/1454)] in the LARS symptom spectrum were significantly alleviated at 12 months (all P<0.05) and remained stable beyond 12 months (all P>0.05). With the extension of postoperative time, the incidence rates of severe LARS exhibited a decreasing trend in different subgroups, of anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma, and reached stability at 12 months postoperatively (all P>0.05). Conclusion:LARS and its specific symptom profile showed a trend of gradual improvement over time up to 1 year postoperatively, and stabilized after more than 1 year. Increased stool frequency and stool clustering are the most common features of abnormal bowel dys function, which improve slowly after surgery.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 &mu;m/year in women and 5.8 &mu;m/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective:To construct polydopamine-coated silicified collagen(SC@PDA)by polymerization of dopamine,and to ex-plore its biological safety and photothermal antibacterial properties.Methods:Dopamine was coated on the surface of silicified colla-gen by polymerization reaction to construct SC@PDA.The surface morphology of SC@PDA was observed by SEM and TEM,the silic-ic acid release was detected by silicic acid release experiment,and the photothermal properties of SC@PDA were detected by 808 nm laser irradiation and infrared thermography.The biocompatibility of SC@PDA was evaluated by CCK-8 assay with rat bone marrow mesenchymal stem cells and acute systemic toxicity test in SD rats.The materials were co-cultured with Staphylococcus aureus(S.au-reus)and Escherichia coli(E.coli)respectively for 6 h followed by 808 nm laser irradiation and culture for 6 h,and then the antibac-terial rate of the materials was calculated by absorbance detection.Finally,the anti-infection effect was observed 7 days after implan-tation in the rat femoral defect infection model of SD rats.Results:SC@PDA maintained the silicic acid release characteristics of si-licified collagen and had good biocompatibility and good photothermal property.In vitro and in vivo antibacterial experiments showed that SC@PDA had good antibacterial activity without cytotoxicity and acut system toxicity.Conclusion:SC@PDA has biocompatibili-ty and the dopamine coating endows the silicified collagen scaffold with excellent photothermal antibacterial properties.

OBJECTIVE To observe the effect of a short course of oral glucocorticoids(GCs)on the expression level of tight junctions(TJs)in the epithelium of nasal polyps.METHODS Patients with chronic rhinosinusitis with nasal polyps(CRSwNP)who were hospitalized for nasal endoscopic surgery were recruited and given oral GCs for 7 consecutive days before surgery.Nasal polyp tissues were harvested before and after GCs treatment respectively.Adult patients who were to undergo nasal endoscopic surgery due to non-inflammatory diseases were selected,and the mucosa of the middle turbinates,inferior turbinates,or uncinate process obtained during surgery was retained as normal controls.Real-time PCR and immunofluorescence confocal microscopy were used to detect the expression of TJs.RESULTS Before oral GCs therapy,the mRNA expression levels of claudin-3,claudin-4,and occludin in nasal polyp specimens were significantly lower than that of normal nasal mucosa.After a short course of oral GCs therapy,the mRNA expression levels of claudin-3 and claudin-4 in nasal polyp specimens were significantly higher than those before treatment.After oral GCs treatment,the protein expression levels of claudin-1 and claudin-4 in nasal polyp tissues were significantly higher than those before treatment.CONCLUSION Compared with normal nasal mucosa,the expression of multiple tight junction proteins in the epithelium of nasal polyps decreases.Short-term oral GCs therapy can significantly up-regulate the expression of tight junction proteins.