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 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 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.

Objectives:To evaluate the imaging effects of the novel sympathetic nerve imaging agent 18F-FPMBBG in healthy volunteers and heart failure patients.Methods:Four healthy volunteers and four heart failure patients were selected to undergo 18F-FPMBBG positron emission tomography/computed tomography(PET/CT)dynamic imaging,the radioactivity distribution characteristics of 18F-FPMBBG in the heart and adjacent organs of the two groups were observed,and the uptake of 18F-FPMBBG by the left ventricular myocardium was compared in the two groups.Results:No adverse effects were observed in all subjects after intravenous injection of 18F-FPMBBG.In healthy volunteers,the heart uptake was rapid and stable,lung uptake was very low,and the blood pool and liver clearance were fast.The heart/liver uptake ratios at 30,60,and 90 minutes after injection were 2.33±0.81,3.29±0.90 and 3.80±1.07,respectively.The average standard uptake value(SUVmean)of 18F-FPMBBG in the heart failure group was significantly lower than that in the healthy volunteer group(P=0.003).The washout rate(WR)was significantly higher in the heart failure group([16.53±2.76]%vs.[3.88±4.51]%,P=0.003).Conclusions:18F-FPMBBG showed good imaging and diagnostic effects in the preliminary imaging of healthy subjects and heart failure patients,and it has the potential to become an ideal cardiac sympathetic nerve imaging agent.

Objective:To analyze the clinical and electrophysiological characteristics of patients with sensory neuronopathies (SNN), and to evaluate the significance of electrophysiological markers in the diagnosis and assessment of disease progression.Methods:A retrospective analysis was performed to evaluate the clinical manifestations, electrophysiological characteristics, and spinal cord magnetic resonance imaging (MRI) features of 8 cases diagnosed with SNN at the Third Central Hospital of Tianjin between 2015 and 2023. The neurophysiological examination mainly included limb nerve conduction study (NCS), same core needle electrode electromyography, somatosensory evoked potential (SEP), skin sympathetic reflex (SSR), and contact heat evoked potential (CHEP).Results:Among the 8 cases with SNN, 7 cases exhibited asymmetrical onset and a non-length-dependent pattern. All the 8 cases presented with severe deep sensory ataxia, accompanied by superficial sensory abnormalities and tendon areflexia. Paraneoplastic SNN were the most prevalent etiological subtype (4 cases), all of whom presented peripheral neuropathy as the initial symptom. Among these 4 cases, malignancies were identified in 3 cases and 3 cases presented with anti-Hu antibodies. Among the remaining 4 patients, 2 cases were autoimmune and the other 2 cases were idiopathic. NCS results of the 8 cases revealed decrease or absence of sensory nerve action potential (SNAP) amplitudes, with normal sensory conduction velocities. Six cases showed abnormal SEP, including 2 cases of central damage and 4 cases of peripheral damage, 5 cases had abnormal SSR, and 2 cases exhibited abnormal CHEP. Motor nerve conduction studies were normal in all 8 cases. Six patients underwent spinal MRI, and 4 exhibited abnormal signals in dorsal columns.Conclusions:The hallmark clinical manifestation of SNN is sensory ataxia, characterized by substantial impairment of superficial sensation, typically manifesting in a non-length-dependent distribution. Beyond the widespread and significant reduction in SNAP amplitudes, SNN may also exhibit additional electrophysiological impairments, such as those observed in SEP, SSR and CHEP.SEP combined with spinal cord MRI can improve the detection rate for damages in the central sensory conduction pathway.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

Objectives:To evaluate the imaging effects of the novel sympathetic nerve imaging agent 18F-FPMBBG in healthy volunteers and heart failure patients.Methods:Four healthy volunteers and four heart failure patients were selected to undergo 18F-FPMBBG positron emission tomography/computed tomography(PET/CT)dynamic imaging,the radioactivity distribution characteristics of 18F-FPMBBG in the heart and adjacent organs of the two groups were observed,and the uptake of 18F-FPMBBG by the left ventricular myocardium was compared in the two groups.Results:No adverse effects were observed in all subjects after intravenous injection of 18F-FPMBBG.In healthy volunteers,the heart uptake was rapid and stable,lung uptake was very low,and the blood pool and liver clearance were fast.The heart/liver uptake ratios at 30,60,and 90 minutes after injection were 2.33±0.81,3.29±0.90 and 3.80±1.07,respectively.The average standard uptake value(SUVmean)of 18F-FPMBBG in the heart failure group was significantly lower than that in the healthy volunteer group(P=0.003).The washout rate(WR)was significantly higher in the heart failure group([16.53±2.76]%vs.[3.88±4.51]%,P=0.003).Conclusions:18F-FPMBBG showed good imaging and diagnostic effects in the preliminary imaging of healthy subjects and heart failure patients,and it has the potential to become an ideal cardiac sympathetic nerve imaging agent.

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective To describe and analyze the epidemiological characteristics of scrub typhus in Huai'an, Jiangsu Province from 2006 to 2024 and explore the long-term incidence trend and distribution of high-risk areas, and to formulate targeted prevention and control strategies. Methods The scrub typhus case report data of Huai'an from 2006 to 2024 in the Chinese Disease Prevention and Control Information System were extracted for descriptive analysis. Results A total of 898 cases of scrub typhus were reported in Huai'an, with an average annual incidence rate of 0.96 per 100 000 from 2006 to 2024. There was a turning point in the incidence trend of scrub typhus in 2011. From 2006 to 2011, the annual percentage change (APC) was 47.09% (95% CI: 7.53 - 859.39), and the upward trend was statistically significant (P < 0.05). From 2012 to 2024, the APC was -2.12% (95% CI: -29.09 - 3.75), and the downward trend was not statistically significant. October and November were the high-incidence months, and the total concentration from 2006 to 2024 was 0.93, indicating that scrub typhus had strict seasonality. The circular distribution method estimated that the peak period of the epidemic was from October 11th to November 25th, and the peak day of incidence was November 3rd. Jinhu County was a high-incidence area. The ratio of male to female cases was 1.03. The age group with the highest reported incidence was 40 to < 80 years old. The occupation with the highest proportion was farmers, accounting for 78.03%. Conclusion From 2006 to 2024, scrub typhus in Huai'an shows a peak every 3 - 4 years. Middle-aged and elderly farmers are the key population at risk, and Jinhu County is a key area. In the future, targeted health education should be carried out to effectively control the prevalence of scrub typhus.