Objective To investigate the protective effect and underlying mechanisms of HydroMg, a novel sustained-release hydrogen donor, in a model of doxorubicin (DOX)-induced chronic cardiotoxicity. Methods H9C2 cells were treated with 1 μmol/L DOX and/or 1 μg/mL HydroMg, and mitochondrial membrane potential, reactive oxygen species (ROS) levels, and apoptosis were measured. In the animal experiment, mice were divided into control, HydroMg, DOX, and DOX＋HydroMg groups. The HydroMg group received intraperitoneal injection of HydroMg (100 mg/kg). Chronic cardiotoxicity was established by intraperitoneal injection of DOX (5 mg/kg every week) for four consecutive weeks; In the DOX＋HydroMg group, HydroMg (100 mg/kg) was administered intraperitoneally 4–5 h prior to each DOX injection. Cardiac function and remodeling were evaluated by echocardiography and heart weight index (HWI). The long-term survival of mice were analyzed. Subsequently, transcriptome sequencing was performed on myocardial tissues from the DOX group to identify key molecular alterations compared with controls. Results At the cellular level, HydroMg treatment effectively reversed DOX-induced mitochondrial dysfunction and oxidative stress, as evidenced by restored membrane potential, reductions in total ROS and mitochondrial superoxide levels by approximately 30% and 9%, respectively, and a decrease in the apoptosis rate from 34.13% to 18.27%. In the animal model, compared with the DOX group, HydroMg intervention increased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) by 9.62% and 5.82%, respectively, attenuated the reduction in HWI (4.41 mg/mm vs 3.53 mg/mm), and improved the 4-week survival rate (80% vs 60%). Transcriptomic analysis revealed that the core molecular features of DOX-induced cardiotoxicity, including widespread suppression of oxidative phosphorylation and antioxidant pathways. Conclusions HydroMg protects against DOX-induced chronic cardiotoxicity by alleviating oxidative stress and improving mitochondrial function, and provides a potential therapeutic strategy against DOX-related cardiotoxicity.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

Objective:To investigate the relationship between sagittal position parameters and screw loosening after unilateral biportal endoscopic (UBE) combined with percutaneous pedicle screw fixation for single-segment lumbar spinal stenosis.Methods:A total of 180 patients with single-level lumbar spinal stenosis who received UBE combined with percutaneous pedicle screw internal fixation in our hospital from June 2020 to June 2023 were enrolled. According to the postoperative follow-up, they were divided into the non-loosening group (112 cases) and the loosening group (68 cases). The demographics, operative parameters and sagittal position [pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), sagittal vertical axis (SVA)] before and after operation were compared between the two groups. The indicators with significant differences between the two groups were included in the multivariate logistic regression analysis to analyze the influencing factors of screw loosening. The dose-response relationship between sagittal position parameters and screw loosening was analyzed by restricted cubic spline model.Results:At 6 months and 1 year postoperatively, the fusion rates in the loosening group were 47.1% and 55.9%, respectively, which were significantly lower than the rates (85.7% and 100.0%) in the non-loosening group, respectively ( P<0.05). Postoperatively, the SS in the non-loosening group (36.16°±5.35°) and the loosening group (32.02°±5.54°) and the LL in the loosening group (51.26°±6.35°) were all significantly lower than preoperative values (40.51°±6.11°, 40.49°±6.08°, and 54.08°±6.21°) ( P<0.05). Meanwhile, the PT in the non-loosening group (15.24°±2.69°), TK in the non-loosening group (32.46°±7.29°), PI in the loosening group (56.82°±5.23°), PT in the loosening group (17.01°±3.64°), and TK in the loosening group (34.87°±7.21°) were all significantly higher than preoperative values (13.12°±3.19°, 30.25°±5.17°, 52.84°±5.12°, 13.15°±3.21°, and 30.26°±5.12°) ( P<0.05). Postoperatively, the loosening group had significantly lower SS (32.02°±5.54°), LL (51.26°±6.35°), and SVA (-0.87±1.06 cm) than the non-loosening group (36.16°±5.35°, 53.73°±6.27°, and -0.51±1.04 cm), respectively ( P<0.05). Conversely, the PI (56.82°±5.23°), PT (17.01°±3.64°), and TK (34.87°±7.21°) in the loosening group were significantly higher than those in the non-loosening group (53.48°±5.20°, 15.24°±2.69°, and 32.46°±7.29°), respectively ( P<0.05). Binary logistic regression analysis indicated that PT, SS, LL, and SVA were independent risk factors for screw loosening ( P<0.05). The restricted cubic spline model revealed a nonlinear dose-response relationship between sagittal parameters (PT, SS, LL, and SVA) and screw loosening ( P<0.05). With increasing PT, the odds ratio (OR) for screw loosening increased, whereas increasing SS, LL, and SVA reduced the OR for screw loosening. Conclusion:After UBE combined with percutaneous pedicle screw fixation in single-level lumbar spinal stenosis patients, sagittal position parameters PT were positively correlated with screw loosening, while SS, LL and SVA were negatively correlated with screw loosening.

Drug clinical trial is a method of experimental epidemiology to evaluate the effectiveness and safety of medicines.This article introduced the types and design thought of innovation in drug clinical trial design,and provided methodological reference for related researches.Adaptive design is a complex and innovative clinical trial design,which can be divided into group sequential design,sample size re-estimation,seamless trial,enrichment design and master protocol design(basket trial,umbrella trial,platform trial,etc.)according to the purpose of adaptability.The adaptive design has greater adjustment flexibility,which overcomes the shortcomings of conventional clinical trials to a certain extent,then improves the validity of the trial results and the strength of the evidence.The design innovation and remodeling of drug clinical trials will provide more powerful evidence-based evidence for the realization of precision medicine.

Objective To investigate Candida albicans(C.auris)colonization in patients and environmental con-tamination of non-intensive care unit(non-ICU)in a hospital,and evaluate the effectiveness of infection prevention and control measures in non-ICU.Methods In March 2024,a paraplegic patient admitted to the department of re-habilitation medicine was found to have C.auris in both urinary catheter and urine culture.The patient was immedia-tely isolated in single room,and patient transfer-in/out of non-ICU was suspended.Fungal cultures were performed on specimens from the ward environment,caregivers,doctors,nurses,and co-hospitalized patients.Mass spec-trometry and molecular biology techniques were used for strain identification and cluster analysis.Contact isolation was conducted on patient.Prevention and control measures were taken,including strict hand hygiene,1 000 mg/L chlorine-based(sodium hypochlorite)disinfection,2％chlorhexidine decolonization,and terminal disinfection of pa-tient-contact items.After discharge,these measures continued with regular C.auris surveillance.Results Five strains of C.auris were isolated from the patient's urine,urinary catheter,inguinal swab,perianal swab,and bed rail swab.Protein mass spectrometry cluster analysis confirmed clonal relatedness of all isolates.The strain showed resistance to fluconazole and amphotericin B,but susceptibility to echinocandins.No C.auris was detected from healthcare workers'hand/axillary/groin swabs.After intervention(such as decolonization and environmental disin-fection),follow-up cultures were negative for C.auris.Conclusion Based on the characteristics of admitted pa-tients,non-ICU should implement active prevention and control measures including:admission screening,contact precautions,object surface microbiological monitoring,decolonization,environmental disinfection,and community management.Hand hygiene,contact isolation,and terminal disinfection are crucial for preventing C.auris trans-mission.