Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective To construct a swallowing dynamic model for simulating dysphagia caused by reduced tongue movement am-plitude.Methods A swallowing dynamic model was established based on medical imaging data from CT and videofluoroscopic swallowing study(VFSS).The finite element method was used to simulate soft tissues,while the smoothed parti-cle hydrodynamics method(SPH)was used to simulate bolus.The model's posture at each time point was com-pared with the imaging data of VFSS from twelve patients with dysphagia,and a normalization method was used for quantitative evaluation of the model's validity.By adjusting the tongue movement amplitude under different viscosity conditions,the role of tongue movement in the swallowing process was investigated,and the swallow-ing safety and efficiency were assessed.Results The tongue posture and bolus trajectory presented by the swallowing dynamic model were consistent with the VFSS imaging.The brightness in the epiglottis area in VFSS images correlated with the equivalent brightness of SPH particles in the simulation results(r=0.97).As the tongue movement amplitude reducing by 20%,the num-ber of aspirated particles,swallowing efficiency and the average velocity of bolus particles in the oropharyngeal cavity all performed well.Pudding-like fluids exhibited favorable swallowing characteristics even when tongue movement amplitude reducing significantly.Conclusion The swallowing dynamic model can simulate the human swallowing process,providing good support for re-habilitation training of patients with dysphagia and the development of specialized medical foods,demonstrating significant potential for clinical applications.

Objective To explore the functional connectivity(FC)changes of hippocampus and amygdala in type 2 diabetes mellitus(T2DM)patients with erectile dysfunction(DMED),and the central pathological neural mechanisms underlying DMED.Methods 61 T2DM patients who visited Department of Endocrinology,Nanjing First Hospital,Nanjing Medical University from January 2020 to December 2021 were selected and divided into a simple T2DM group(n=30)and a combined DMED group(n=31).Another 47 healthy individuals were selected as control group(NC).The international erectile function scale(IIEF-5)was used to evaluate the erectile function.Resting-state functional magnetic resonance imaging(rs-fMRI)data were acquired from all participants.MRI data were preprocessed by the DPABI software package.Bilateral hippocampus and amygdala were selected as regions of interest(ROI)and the whole brain FC values were calculated.The FC values of brain regions between groups were tested by two-sample t-test with REST software package.Results Left hippocampus as ROI:compared with the NC group,FC values of the left superior temporal gyrus increased in the T2DM group,FC values of the left superior frontal gyrus,left inferior temporal gyrus,left posterior central gyrus and rectus gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left inferior parietal gyrus,left supramarginal gyrus,left middle occipital gyrus and right posterior central gyrus decreased in the DMED group.Right hippocampus as ROI:compared with the NC group,FC values of the right middle temporal gyrus and right rolandic operculum increased while FC values of the right calcarine fissure decreased in the T2DM group;FC values of bilateral anterior cingulate gyrus,right middle temporal gyrus and left rectus gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus,left inferior parietal gyrus and right inferior temporal gyrus decreased in the DMED group.Left amygdala as ROI:compared with the NC group,FC values in the left parahippocampal gyrus,left fusiform gyrus and right insula increased in the T2DM group;FC value of the left middle temporal gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus and left supramarginal gyrus decreased in the DMED group.Right amygdala as ROI:compared with the NC group,FC values of the left insula,right parahippocampal gyrus,right superior temporal gyrus and right supramarginal gyrus increased while FC values in the right caudate decreased in the T2DM group;FC values of the right middle frontal gyrus,left rectus gyrus and left middle occipital gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus and left inferior parietal gyrus decreased in the DMED group.Conclusions DMED patients have abnormalities in the hippocampus,amygdala and other brain regions,especially the frontal lobe functional cortex,which may be related to changes in their brain function.

Clinical practice guideline adaptation(hereinafter referred to as"guideline adaptation")is the consolidation and revision of existing high-quality guidelines so that the recommendations are better suited to the specific needs of different regions,thereby guiding optimal clinical practice.Currently,the guideline adap-tations is increasing in number internationally,but their reporting quality still needs to be improved.In 2022,the RIGHT-Ad@pt guideline adaptation reporting checklist was released.It provides a detailed description of the guideline adaptation process and reporting content,which will significantly enhance the rigor,transparency,and standardization of guideline adaptations.This paper interprets and analyzes the 34 items on the checklist,with the aim of providing reference for guideline adapters to standardize the reporting process.

Objective:To explore the clinical value of multi-parameter combined monitoring in guiding low-molecular-weight heparin (LMWH) therapy for intensive care unit (ICU) patients.Methods:A retrospective case-control study was conducted. A total of 381 patients who received LMWH therapy with anti-Ⅹa activity monitoring in the ICU of West China Hospital, Sichuan University between January 31st, 2022, and November 30th, 2023, were enrolled in this study. The cohort comprised 264 males and 117 females, with the age of 58 (48, 71) years old. Clinical data and relevant laboratory parameters were collected, including anti-Ⅹa activity, antithrombin activity (AT), thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PIC), conventional coagulation parameters such as activated partial thromboplastin time (APTT), and indicators of hepatic/renal impairment such as alanine aminotransferase (ALT) and creatinine( CREA). Patients were stratified into three groups based on thrombotic event: thrombosis-controlled, progressive thrombosis, and bleeding group. Single-factor and adjusted multifactorial Logistic regression analysis were used to identify independent predictors of anti-xa activity levels.Results:Among 381 patients, thrombosis was controlled in 213 (55.9%) patients, progressed in 81 (21.3%) patients , and bleeding events occurred in 87 (22.8%) patients. The patients whose anti-Ⅹa activity levels lay entirely within the target range(0.2-0.4 IU/ml): Only 35 (16.4%) cases in the thrombosis-controlled group, 16 (19.7%) cases in the progressive thrombosis group, and 16 (18.4%) in the bleeding group. No significant differences in anti-Ⅹ a levels activity among the three groups ( H=1.678, P=0.432). Both single-factor and adjusted multifactorial Logistic regression identified low AT activity as an independent risk factor for failure to achieve target anti-Ⅹ a activity levels (AT nadir, OR=1.031,95% CI 1.016-1.046, P<0.05). Compared with the progressive thrombosis and bleedinggroup, the thrombosis-controlled group exhibited significantly higher proportion of TAT values below the cut-off value ( H=8.519, P=0.014), and a higher proportion of TAT/PIC ratios below the cut-off ( H=15.56, P<0.001). Patients with bleeding demonstrated significantly lower AT activity ( H=14.968, P=0.001), prolonged APTT ( H=6.815, P=0.033), higher ALT ( H=13.774, P=0.001), and higher CREA ( H=14.068, P=0.001) compared with the thrombosis-controlled or progressive thrombosis group. Conclusion:Laboratory monitoring is required for low-molecular-weight heparin (LMWH) therapy in ICU patients. While anti-Ⅹa activity reflects the anticoagulant effect of LMWH, the utility of anti-Ⅹ a activity for predicting thrombotic or hemorrhagic risks in LMWH treated ICU patients is limited. Reductions in TAT levels and TAT/PIC ratios are associated with a lower risk of thrombotic progression. Furthermore, abnormalities in conventional coagulation tests and standard hepatic/renal function parameters occur more frequently in patients experiencing hemorrhagic events.

Purpose To investigate the clinicopathological characteristics of the gastric oxyntic gland adenoma(GOGA).Methods We collected 18 samples of GOGA,histopathological features and immunohistochemical staining were assessed.Main features of pathological diagnosis,treatment methods and follow-up were retrospectively analyzed.Results There were 18 patients,including 9 females and 9 males,aged from 36 to 86 years old.The endoscopic im-age showed a flat lesion with whitish in color or a polypoid protrusions.The size ranged from 0.3 cm to 0.8 cm.Hema-toxylin and eosin staining showed irregular glandular structures in the mucosal lamina propria,with branched and anas-tomosed patterns.The tumour demonstrating composed of chief cells hyperplasia with mild nuclear atypia.All lesions were confined to the mucous lamina propria.There was no atrophic within the peripheral gastic mucosa.Immunohisto-chemical examination showed positive for Pepsinogen-Ⅰ and MUC6.Gene mutation were analyzed in 2 cases using next generation sequence technology,and no KRAS and GNAS mutation had been detected.Endoscopic surgical treatment was performed in 11 cases,and biopsy forceps removal was carried out in 7 cases.No recurrence or metastasis was ob-served during the follow-up period of 1 to 58 months.Conclusion GOGA is a rare lesion,and appears to behave bio-logically benign.A full understanding of its histological morphology and biological behavior can improve the diagnostic ability of clinincans,and facilitate further research in the future.

Objective To investigate the value of whole lung CT radiomics combined with clinical and conventional CT features for differentiating non-tuberculous mycobacterial pulmonary disease(NTM-PD)and pulmonary tuberculosis(PTB).Methods Fifty-three NTM-PD(NTM-PD group)and 111 PTB(PTB group)patients diagnosed by mycobacteria culture were retrospectively collected.The patients were divided into training set(n=115,including 37 cases of NTM-PD and 78 cases of PTB)and test set(n=49,including 16 cases of NTM-PD and 33 cases of PTB)at the ratio of 7∶3.Patients'clinical and pulmonary CT manifestations of lesions were analyzed using univariate and multivariate logistic regression,and the independent impact factors for differentiating NTM-PD and PTB lesions were screened.The best radiomics features were extracted and screened based on whole lung CT.Based on independent impact factors,the best radiomics features and their combination,clinical-CT,radiomics and combined models were constructed with random forest,and the differential efficacy of each model was evaluated.Results Patients'age(OR=0.264),gender(OR=0.956),immunoglobulin G(OR=3.416),C reactive protein(OR=3.418)and bronchiectasis shown on CT(OR=0.285)were all independent impact factors for differentiating NTM-PD and PTB.Twelve best radiomics features were screened based on whole lung ROI.The AUC of combined model in training set and test set was 0.915 and 0.901,respectively,both higher than that of clinical model(AUC=0.832,0.801,Z=1.340,3.710,both P＜0.05)and radiomics model(AUC=0.877,0.821,Z=-2.520,-5.240,both P＜0.05).Conclusion Whole lung CT radiomics combined with clinical and conventional CT features could effectively distinguish NTM-PD and PTB.

Objective:Given the insufficiency of current clinical biomarkers for early diagnosis of esophageal adenocarcinoma(EAC),this study developed a panel of serum protein biomarker assays using liquid-phase chip technology and preliminarily validated the detection capabilities of these markers for EAC.Methods:Collected serum samples from 48 patients with EAC and 33 age-matched healthy controls(HC).The levels of squamous cell carcinoma antigen(SCCA),human cytokeratin 19 fragment(Cyfra21-1),hepatocyte growth factor(HGF)and IL-8 in serum were analyzed by liquid chip technology.The diagnostic efficacy of a single indicator and a combination of four indicators were evaluated by receiver operation characteristic(ROC)curve.Results:The detection ranges of SCCA,Cyfra21-1,HGF and IL-8 were 0.24～1 000 ng/ml,45.72～100 000 pg/ml,21.95～16 000 pg/ml,and 0.61～10 000 pg/ml,respectively.The liquid chip technology shows a strong correlation with clinical chemiluminescence immunoassay(r=0.949 4,P<0.000 1)and ELISA technology(r=0.955 1,P<0.000 1).Compared to the HC group,serum levels of SCCA and HGF were signifi-cantly elevated in the EAC group(P<0.01),IL-8 was significantly decreased(P<0.05),while Cyfra21-1 shows no significant difference(P>0.05).In the early EAC group,serum HGF was significantly higher than in the HC group(P<0.01).ROC curve analysis shows that among individual markers,HGF exhibits the best diagnostic efficacy for early EAC with an area under the curve(AUC)of 0.761,while the AUC for the combination of the four biomarkers was 0.857,both superior to the clinical biomarkers SCCA(AUC=0.604)and Cyfra21-1(AUC=0.515).Conclusion:Liquid chip technology is used to jointly detect SCCA,Cyfra21-1,HGF,and IL-8 in human serum.In the early diagnosis of EAC,the diagnostic efficacy of the combined use of these four biomarkers is superior to that of the commonly used clinical tumor markers SCCA and Cyfra21-1.This advantage stems from the high throughput and high sensitivity characteristics of liquid-phase chip technology.Consequently,this combined detection method holds significant clinical application and is expected to provide a more accurate and reliable tool for the early diagnosis of EAC.

With the rapid advancement and iterative development of new artificial intelligence technologies, there remains a regulatory vacuum in corresponding governance measures among governments worldwide. Simultaneously, a technological and governance gap exists between developing countries and developed economies. In response, the World Health Organization (WHO) has released "Ethics and Governance of Artificial Intelligence for Health: Guidance on Large Multi-Modal Models" to assist governments in strengthening governance capabilities in this field. This paper provides an in-depth analysis of the Guidance, aiming to identify challenges and risks associated with the application of multimodal large models in healthcare. Guided by ethical principles for advancing health through artificial intelligence, the paper examines the three-tier governance framework and recommendations outlined in the Guidance. Additionally, it evaluates the current state of AI governance in China, offering insights and reference points for improving AI governance in China′s healthcare sector.

Objective·To investigate the genetic etiology of a rare and complex case clinically suspected to be methylmalonic acidemia(MMA),but with negative whole exome sequencing(WES)results,using a multi-omics sequencing approach.Methods·DNA and RNA samples were extracted from the peripheral blood of the proband and both parents.Targeted MMA-related gene Panel sequencing and WES were first performed.Subsequently,RNA sequencing(RNA-seq)and whole genome sequencing(WGS)were conducted to comprehensively analyze the child's genetic variants,their origins and potential inheritance patterns.Results·No pathogenic variants associated with the patient's phenotype were identified through the MMA Panel or standard WES analysis.Extended analysis of WES suggested the possibility of uniparental disomy(UPD)of chromosome 4.WGS revealed a homozygous splice-site variant(c.-66+2T>C)in the non-coding region of the metabolism of cobalamin associated A(MMAA)gene.The variant was located in the 5'untranslated region(5'UTR),specifically at the second base downstream of the splice donor site of exon 1(reference sequence:NM_172250).In genomic coordinates(hg19),the variant was located at base 146540561 on chromosome 4(chr4:146540561).Sanger sequencing confirmed that the mother was heterozygous for this variant,while the father did not carry it.RNA-seq showed no detectable expression of the MMAA gene on chromosome 4 in the patient.This was further confirmed by reverse transcription real time quantitative PCR,indicating nearly absent mRNA expression,suggesting that the non-coding splice-site variant affected transcriptional expression.Conclusion·A homozygous splice-site variant(c.-66+2T>C)in the non-coding region of the MMAA gene—outside the coverage of WES—is likely the pathogenic cause in this case,presumably resulting from maternal UPD of chromosome 4.