Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Objective:To investigate whether repeated tirofiban injections can continuously inhibit platelet aggregation in the arterial duct and affect its closure in neonatal canines.Methods:Four 24-month-old pregnant beagles underwent cesarean sections in two batches (two dogs per batch) 1-2 days before the expected delivery date at the Xuzhou Medical University Animal Experiment Center. The first litter of 21 neonates served as the control group (receiving 10 ml/kg normal saline) and were randomly divided into 1-h ( n=7, injected immediately after birth), 4-h ( n=7, injected at 0 h and 2 h after birth), and 12-h subgroups ( n=7, injected at 0 h, 2 h, 4 h, 6 h, 8 h, and 10 h after birth). The second litter of 18 neonates served as the experimental group (receiving 10 ml/kg tirofiban) with identical subgroup assignments ( n=6 per subgroup). Echocardiography was performed at 1 h, 4 h, and 12 h after birth to measure arterial duct inner diameter, maximum shunt velocity, and left atrial diameter/aortic root diameter (LA/Ao) ratio. Plasma platelet-derived growth factor (PDGF) was detected by enzyme-linked immunosorbent assay, while platelet membrane glycoprotein Ⅱb-Ⅲa in the arterial duct was assessed by Western blot and immunohistochemistry. Data were analyzed using t-tests, one-way ANOVA, Chi square tests, or Fisher's exact test. Results:No significant bleeding tendency occurred in either group. Two control neonates (one each in the 4-h and 12-h subgroups) died. In both control and experimental 1-h subgroups, all arterial ducts remained open, with no significant differences in ductal diameter, shunt velocity, or LA/Ao between groups (all P>0.05). In the 4-h subgroups, all experimental neonates had patent ducts arteriosus, while two controls exhibited closure; the experimental group had larger ductal diameters [(1.05±0.05) vs. (0.55±0.44) mm, t=－2.75, P<0.05)] and higher LA/Ao ratios (1.31±0.09 vs. 1.14±0.03, t=－4.90, P<0.05), but lower maximum shunt velocities [(107.06±17.47) vs. (153.74±12.78) cm/s, t=4.54, P=0.002). In the 12-h subgroups, all the controls had closed arterial ducts, while four of six experimental neonates exhibited closure, though the difference in closure rate was not statistically significant (6/6 vs. 4/6, Fisher's exact test, P=0.455). Plasma PDGF and glycoprotein Ⅱb-Ⅲa levels did not differ between two 1-h subgroups (all P>0.05). However, the 4-h and 12-h experimental subgroups showed lower PDGF levels [(373.5±13.1) vs. (880.3±80.2) pg/ml, t=10.81; (356.7±35.0) vs. (1 111.2±125.3) pg/ml, t=9.74; both P<0.05] and reduced glycoprotein Ⅱb-Ⅲa expression (0.32±0.07 vs. 0.80±0.23, t=3.29; 0.42±0.07 vs. 0.92±0.26, t=3.24; both P<0.05) compared to controls. Conclusion:Repeated tirofiban injections sustainably inhibit platelet aggregation in the arterial duct of neonatal canines and delay ductal closure, suggesting that intraductal platelet aggregation may be one factor influencing this process.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective To determine the diagnostic criteria of quantitative syndrome differentiation of toxin syndrome of diabetic kidney disease.Methods The questionnaire scale was developed through literature research and expert consultation.Points were assigned for the 5 major symptoms in 294 patients with DKD,and according to the TCM syndrome differentiation standard of toxic syndrome syndrome formulated by experts,it is divided into toxic syndrome group and non-toxic syndrome group.The symptom items were screened from the aspects of sensitivity,differentiation and representativeness by statistical method,and the weight value of the items was given by factor analysis.The threshold and the best diagnosis model were determined under the ROC curve.Finally,through the verification group data to verify the scale model,evaluate the diagnostic ability of the scale,and finally construct the diagnostic standard scale model of DKD toxin syndrome.Results 14 symptom items were selected as TCM related symptoms of DKD toxin syndrome,and the diagnostic threshold was determined to be 140.The diagnostic criteria of quantitative syndrome differentiation of DKD toxin syndrome were as follows:total score=fatigue * 10+edema * 10+turbid urine * 10+sore waist and knees * 10+dizziness * 10+tongue purple * 10+dark complexion * 9+limb numbness * 8+loose stools * 7+dry mouth * 4+dry eyes * 4+frequent urination at night * 3+abdominal distension * 3+greasy moss * 3.The degree of each item without this symptom should be multiplied by weight value by 0,mild by weight by 1,moderate by weight by 2,severe by weight by 3,and the total score≥140 could be diagnosed as toxin syndrome.The verification results showed that the sensitivity of the study group was 92.24%,the specificity was 96.19%,the Kappa value was 0.882,and the sensitivity,specificity and Kappa value of the verification group were 87.50%,96.97%and 0.836,respectively.Conclusion The standard scale of DKD toxin syndrome differentiation and diagnosis is constructed,and it has good diagnostic ability,which provides certain application value for clinical and scientific research.

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 explore the the possibility and potential mechanism of Coptis chinensis in treating caries based on network pharmacology and molecular docking technology.Methods:The active ingredients of Coptis chinensis and the targets of the active in-gredients and caries were obtained through a variety of databases.The intersection targets of Coptis chinensis and caries were obtained by VENNY.Based on the target of the intersection,the protein-protein interaction(PPI)networks relationship diagram was formed on the STRING platform.The core target diagram was formed through the Cytoscape software,and the Coptis chinensis-active ingre-dient-target network diagram was constructed.The intersection targets are analyzed by GO and KEGG.The core targets of Coptis chinensis active ingredients in treating caries was analyzed by molecular docking.Results:The 11 Coptis chinensis active ingredi-ents,465 targets of Coptis chinensis active ingredients and 1 160 targets of caries were obtained from the database.After analysis,71 targets of Coptis chinensis-caries intersection and 12 core targets were obtained.The potential therapeutic effect of Coptis chinensis on caries involved relaxin,phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt),mitogen activated protein kinase(MAPK),ras-re-lated protein 1(RAP1)and other signaling pathways.Berberine,one of the main active components of Coptis chinense,had strong binding activity on epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9)and other core targets.Coptis chinen-sis and its active components can play a role in the treatment of caries through EGFR,MMP9 and PI3K-AKT,MAPK and other path-ways.Conclusion:Coptis chinensis and its active components can regulate several targets and signaling pathways such as EGFR,MMP9,PI3K-AKT and MAPK.Coptis chinensis may play a role in the prevention and treatment of caries through multiple pathways.

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.