Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

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 fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

ObjectiveTo analyze the clinicopathological features of patients with comorbidities of chronic hepatitis B （CHB） and steatotic liver disease （SLD）， to investigate the impact of hyperglycemia on the risk of liver fibrosis and end-stage liver diseases （ESLD）， and to provide a basis for the clinical management of such population. MethodsA total of 668 adult patients with CHB-SLD confirmed by liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from January 2011 to December 2019 were enrolled， and a retrospective cohort was established with the time of liver biopsy as the baseline and the onset of ESLD as the endpoint. All patients were followed up to March 31， 2024. Propensity score matching （PSM） was performed at a ratio of 1∶4 to balance baseline features between groups， resulting in 82 patients in the hyperglycemia group and 281 in the non-hyperglycemia group. The two groups were compared in terms of metabolic profiles， laboratory markers， and histopathological features. The Mann-Whitney U test was used for comparison of non-normally distributed quantitative data between two groups. The chi-square test or Fisher exact test was used for comparison of categorical data between two groups. A multivariate Logistic regression analysis was used to investigate the influencing factors for advanced fibrosis （AF）， and the Kaplan-Meier survival analysis and the Cox proportional-hazards regression model were used to determine the influencing factors for the development of ESLD. ResultsCompared with the non-hyperglycemia group， the hyperglycemia group had a significantly higher number of factors for metabolic disorders， a significantly higher degree of hepatic steatosis， and a significantly higher detection rate of AF （all P<0.05）. The multivariate Logistic regression analysis showed that hyperglycemia was a risk factor for AF （odds ratio = 1.753， 95% confidence interval ［CI］： 1.017　—　3.023， P=0.043）. The survival analysis showed that hyperglycemia increased the risk of ESLD （χ²=4.340， P=0.037）. The multivariate Cox regression analysis confirmed that hyperglycemia was a significant metabolic risk factor for ESLD in patients with AF （adjusted hazard ratio=3.208， 95%CI： 1.201　—　8.568， P=0.020）. ConclusionHyperglycemia can increase the risk of AF and ESLD in CHB-SLD patients. Clinical monitoring and active management should be strengthened for patients who have already developed AF and hyperglycemia.

Objective To verify the applicability of a pig STR multiplex amplification system for detecting processed foods containing pork and their digestive samples,and to evaluate its potential in food safety and forensic biological evidence analysis.Methods DNA profiles were obtained using the pig STR amplification system from food samples with different levels of processing(raw pork,boiled pork,fried pork,and sausage)and from digestive samples(rat gastric contents).The influence of processing methods on DNA integrity was assessed.The uniformity of large-scale processed ham products,the consistency of DNA profiles from different parts of the same sample,and the DNA degradation patterns after rat digestion were examined.Results STR profiling of pig DNA was successful in all tested samples.Short fragments showed high amplification stability,while long fragment signals weakened with increasing processing complexity.In processed ham products,DNA profiles were consistent across all sampled parts,with fragment drift within±0.5 bp.Analysis of rat gastric contents showed slight DNA degradation within 2 hours;after 3 hours,long fragment signals weakened,and after 4 hours,some loci signals were lost.Conclusion The pig STR multiplex amplification system exhibits excellent performance in detecting processed pork products and their digestive samples.It can meet the requirements of food traceability and forensic biological evidence analysis for processed pork,providing new insights for the advancement of forensic testing techniques in this field.

Objective To investigate the value of double low-dose iterative reconstruction CT features combined with serum lung cancer autoantibodies in the diagnosis of stage ⅠA lung cancer.Methods The data of 168 patients with suspected stage ⅠA lung cancer were retrospectively analyzed,and all of them underwent double low-dose iterative reconstruction CT and serum lung cancer autoantibodies examination before treatment.Based on the pathological results as the gold standard,the patients were divided into stage ⅠA lung cancer(119 cases)and benign lesion(49 cases),the diagnostic value of double low-dose iterative reconstruction CT features,serum lung cancer autoantibodies alone and combined both methods in stage ⅠA lung cancer was analyzed.Results Compared with the non-iterative reconstruction CT,the iterative reconstruction CT had significantly lower noise values and significantly higher signal-to-noise ratio and image quality scores(P<0.05).The maximum enhanced CT value and the maximum difference between pre-and post-enhanced CT in stage ⅠA lung cancer were lower than those in benign lesion(P<0.05).The levels of tumor protein 53(p53),stem cell transcription factor 2(SOX2),tumor testicular antigen 7(GAGE7),tumor antigen 4-5(GBU4-5),melanoma antigen A1(MAGE A1),and human carcinoma antigen(CAGE)were higher in stage ⅠA lung cancer than those in benign lesion(P<0.05).The receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)of double low-dose iterative reconstruction CT,serum lung cancer autoantibodies,and the combination of both in the diagnosis of stage ⅠA lung cancer were 0.818[95%confidence interval(CI)0.744-0.893],0.744(95%CI 0.655-0.832),and 0.876(95%CI 0.807-0.945),respectively.Conclusion Double low-dose iterative reconstruction CT features combined with serum lung cancer autoantibodies has high sensitivity and specificity in the diagnosis of stage ⅠA lung cancer.

Enhancing the antimicrobial stewardship level is an important issue in curbing the development and spread of microbial resistance as well as maintaining the health of the people.This study reviews the current situa-tion of antimicrobial application both in China and abroad,sorts out the history of antimicrobial management,finds out the existing problems in the current work,and puts forward measures including attaching importance to patho-gen detection,improving the infection control strategy for antimicrobial-resistant organisms,establishing a multile-vel service mechanism,forming a multidisciplinary core team,and perfecting the management system,so as to pro-vide references for actively responding to the challenges posed by antimicrobial resistance.

Objective To compare the performance of 3 risk prediction models based on machine learning in predicting the risk of compassion fatigue among obstetrics and gynaecology nurses.Methods Using the convenience sampling method,1 323 obstetrics and gynaecology nurses from 11 tertiary hospitals in 9 cities were selected from December 2022 to March 2023,and were randomly divided into a training set and a test set according to 7∶3 ratio.Compassion Fatigue Scale,Five Facet Mindfulness Questionnaire and Emotional Intelligence Scale were used for the survey.A total of 3 types of risk prediction models were constructed for the factors affecting the compassion fatigue of obstetrics and gynaecology nurses,namely,Logistic Regression,Decision Tree,and Random Forest.The accuracy,precision,specificity,sensitivity,Fl score and AUC were used to compare the predictive performance of the 3 models.Results Finally 1 276 maternity nurses completed the survey.All 3 models showed that nature of employment,years of experience,mindfulness and emotional intelligence were independent risk factors for compassion fatigue in obstetrics and gynaecology nurses(P＜0.05).The results of model comparison showed that the accuracy of Logistic regression,decision tree and random forest were 0.804,0.806,0.796;the precision was 0.821,0.827,0.823;the sensitivity was 0.956,0.949,0.939;the Fl score was 0.883,0.884,0.877;the AUC was 0.704(95％CI:0.701～0.713),0.760(95％CI:0.751～0.771),0.742(95％CI:0.723～0.762)respectively.Conclusion The risk prediction model of factors affecting compassion fatigue among obstetrics and gynaecology nurses constructed by decision tree performed the best,and the predictive performance was better than that of the random forest and logistic regression models.The multi-model effectively predicts the risk of compassion fatigue in obstetrics and gynecology nurses,explores the interaction of influencing factors in multiple dimensions,and it can inform the early identification and prevention of compassion fatigue and the development of related interventions.

OBJECTIVE To investigate the changes of air aerosols in the digestive endoscope cleaning and disinfec-tion room under real working conditions and observe the purification effects of aerosols under different ventilation and disinfection modes.METHODS Under the real working conditions(with both the air conditioner and recircu-lating air disinfection machine under the working mode),the air samples were collected every 1 hour from 8:00 to 16:00 from the digestive endoscope cleaning and disinfection room of Ren Ji Hospital,Shanghai Jiao Tong U-niversity School of Medicine from May 2023 to Oct.2023;the contents of particulate matters(PM)and microor-ganisms in the air were detected.At the busiest moment of the cleaning and disinfection room,the air was respec-tively sampled from the cleaning and disinfection room with the working condition modes of air condition systems,recirculating air disinfection machine or natural ventilation before the starting of systems and after the work for 0.5 hour,1 hour and 2 hours.The contents of PMs and microorganisms were detected.RESULTS The PM0.5 con-centrations during various time periods met the Grade 9 ISO clean room standard(≤35,200 particles/L)under the real working conditions,and the content of airborne viable particles also conformed to the Class Ⅲ environmental requirements(≤500 CFU/m3).All of the three ventilation and disinfection methods showed certain effects on purification of the con-tents of PM0.5 and microorganisms after the ventilation for 2 hours,the contents of PMs and microorganisms of the air disinfection machine group decreased most remarkably,followed by the air conditioner group,the natural ventilation group the least.There were no significant differences in the PM concentration and the content of microorganisms among the three groups at the time points;there were only significant differences in the PM concentration and the content of mi-croorganisms of the air disinfection machine group after the ventilation for 2 hours,0.5 hour and 1 hour(P＜0.05).CONCLUSIONS Both the air conditioning systems and recirculating air disinfection machine under the working con-dition mode have certain effect on purification of the contents of PM and microorganisms,and the specific effect need to be further studied.The implementation of multicenter dynamic surveillance with the help of intelli-gent techniques may provide reference for the optimization of ventilation and disinfection strategies.

The incidence of apoplexy remains persistently high among the older population.Based on the traditional Chinese medicine principle of"treating the elderly by focusing on the fu",this paper explores the holistic connotation of"fu".It proposes that the onset of apoplexy in the elderly is characterized by obstruction,stagnation,depression,and sluggishness,which should be treated from six fu viscera,xuanfu,and collaterals.The interconnected hierarchical network of these three systems,serving as macro-and micro-channels for qi and fluid metabolism,plays a central role in both disease development and treatment.The failure of the six fu viscera to descend and the upward invasion of turbid yin are identified as prerequisites for apoplexy onset,whereas yang qi stagnation and xuanfu blockage act as key pathogenic drivers,and the core mechanisms involve phlegm-stasis-toxin accumulation,and dysfunction of the collaterals and fu.In the treatment,acute phase requires unblocking fu viscera and restoring xuanfu patency;chronic phase focuses on dredging collaterals and opening xuanfu;and recovery phase emphasizes tonifying combined with regulating xuanfu.The understanding of"treating the elderly by focusing on the fu"emphasizes that the pathogenesis of the disease should be changed to individual conditions;"six fu viscera-xuanfu-collaterals"exhibits a pathological mechanism characterized by the transmission and reception of pathogenic factors,as well as progressive mutual involvement;in clinical practice,treatment should meticulously assess the severity and nuances of the condition,prioritizing method that emphasizes unobstructed flow;additionally,therapy should be essential to protect stomach qi and integrate therapeutic attacks within a framework of supplementation.These principles offer valuable reference for the differentiation and treatment of apoplexy.