BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC. METHODS: Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes. RESULTS: A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways. CONCLUSIONS The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Prognosis ; ROC Curve ; Middle Aged

ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

Objective To observe the effect of specialist team-led walking-cognition dual-task train-ing combined with active self-disclosure on control and balance abilities in elderly patients with acute ischemic stroke(AIS).Methods A total of 90 elderly AIS patients treated in our hospital from January 2022 to January 2024 were enrolled and randomly assigned into the control group and the observation group,with 45 cases in each group.The control group received routine walk-ing training,while the observation group received specialist team-led walking-cognition dual-task training combined with active self-disclosure intervention.Control ability,balance ability,walking ability,cognitive function and psychological status were compared between the two groups.Results After intervention,the scores of Sheikh Trunk Control Scale and Fugl-Meyer Assessment(FMA),and the static balance score,dynamic balance score and total score of Berg Balance Scale(BBS)were significantly increased in both the observation and the control groups(P＜0.05),and all above scores were obviously higher in the former group than the latter one(P＜0.01).The two groups also obtained notably shorter single-and dual-task walking time after intervention,but there were no statistical difference in the single-task walking time in both groups before and after intervention(P＞0.05).After intervention,the observation group had significantly shorter dual-task walking time(22.87±7.36 s vs 27.52±8.71 s,P=0.008)and lower walking time cost of dual task[(11.16±4.07)％vs(25.61±7.82)％,P=0.000]when compared with the control group.After intervention,the scores of Mini-Mental Status Examination were increased,and the scores of Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale were decreased in the two groups(P＜0.05).Conclusion Specialist team-led walking-cognition dual-task training com-bined with active self-disclosure intervention can effectively improve trunk control ability,balance ability,walking ability,cognitive function and psychological state in elderly AIS patients,has cer-tian clinical application value.

Traditional Chinese herbal medicine (TCM) has been used in China for thousands of years as an integral part of the healthcare system.The use of botanical products deriving from plants from TCM has become very spread and rooted in European Union (EU), generating a manufacturing industry of pronounced size, in particular the segment of food supplements, but recently also medical devices and cosmetics based on plants from TCM, especially in Italy. Only seven Herbal Medicinal Products (HMP) based on plants from TCM are present in EU besides more than 100 monographs on TCM plants are present in the European Pharmacopoeia. Indeed, the number of herbal monographs of European Medicine Agency (EMA) which report the main data on safety and efficacy of medicinal plants from TCM are very limited and this could be a reason for the limited number of HMP based on herbal drugs used in TCM. It is clear that those botanicals based on TCM but not classified as HMP can represent a sort of "borderline" products. Very likely, they are present on the European market because of the simpler authorization when compared with HMP. Some examples of these categories (food supplements and medical devices) containing plants from TCM and marketed in Italy are reported in this review. Consequently, it is urgent the need to clarify their categorization, also fundamental for the consumer protection. It is imperative the establishment of EU quality standards and official registration for Chinese herbal medicinal products, even if they are marketed as food supplements, medicinal devices or cosmetics because the international quality standards International Organization for Standardization Technical Committee 249-Traditional Chinese Medicine (ISO/TC249) can harmonize the quality control and promote the trading internationally. Governmental organizations together with companies producing TCM should work together to accelerate the legislation of laws pertaining to TCM, and generate an environment where TCM does not just continue to exist but truly develop.

The healing of the alveolar socket following tooth extraction is a complex process,which is influenced by multiple factors.After tooth extraction,the soft and hard tissues surrounding the extraction site undergo remodeling.During this process,systemic factors and local anatomical structure of the extraction site play a significant role.This review provides a detailed discussion of the alveolar socket healing process and its potential influencing factors.It aims to offer clinicians a comprehensive reference when assessing the healing potential of different extraction sites,thereby providing more informed and precise clinical decision-making.

Objective:To investigate the clinical characteristics of children with severe human metapneumovirus (HMPV) infection and identify the risk factors associated with critical illness.Methods:A retrospective cohort study was conducted, enrolling 157 hospitalized children with severe HMPV infection, who tested positive for HMPV nucleic acid via PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at Shanghai Children′s Hospital from January 2021 to December 2023.Clinical features, co-infections, treatment, and outcomes were collected. Based on the diagnostic criteria for severe HMPV infection, the patients were categorized into a critical illness group and a non-critical illness group. Intergroup comparisons were performed using the χ2 test or the Mann-Whitney U test. Multivariate Logistic regression analysis was employed to identify risk factors for critical HMPV infection and to establish a predictive model.The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and calibration curves. Results:Among the 157 cases of severe HMPV infection, there were 67 males and 90 females, with an onset age of 39.0 (20.0, 55.5) months. Single-pathogen infection was observed in 125 cases (79.6%), while mixed infections accounted for 32 cases (20.4%).Severe pneumonia was diagnosed in 136 cases (86.6%).The predominant manifestations of severe HMPV infection included fever 152 cases (96.8%), cough 151 cases (96.2%), and wheezing 94 cases (59.9%).Sixty-eight patients (43.3%) required non-invasive respiratory support, 58 cases (36.9%) were admitted to the intensive care unit, and 22 cases (14.0%) underwent mechanical ventilation. Of the total, 149 cases (94.9%) were discharged with improvement, 8 cases (5.1%) were discharged against medical advice, and there were no fatal cases. The cohort was further stratified into a critical illness group 31 cases and a non-critical illness group 126 cases. Compared to the non-critical illness group, the critical illness group exhibited significantly higher rates of respiratory distress, lethargy, and intercostal retractions, along with a higher proportion of underlying comorbidities, and elevated levels of C-reactive protein and procalcitonin (all P<0.05).Conversely, albumin and hemoglobin levels were significantly lower in the critical illness group (both P<0.05). ROC curve analysis revealed that the optimal cutoff value for the duration of fever in predicting severe HMPV infection was 4.5 days.The multivariate binary Logistic regression analysis revealed that prolonged fever duration (>4.5 days) ( OR=28.00, 95% CI 5.09-153.93, P<0.001), anorexia ( OR=11.72, 95% CI 1.26-108.75, P=0.030), and immune dysfunction ( OR=36.71, 95% CI 1.55-867.31, P=0.026) were independent risk factors for severe HMPV infection. A predictive model for critical illness was constructed based on these independent risk factors. ROC curve analysis demonstrated excellent discriminative ability, with an area under the curve of 0.96 (95% CI 0.92-1.00, P<0.001). The optimal predictive probability threshold was 0.17, yielding a sensitivity of 0.93 and specificity of 0.92. The calibration curve closely approximated the ideal curve, indicating good model calibration ( P=0.157). Conclusions:Severe HMPV infection is predominantly observed as a single infection and is prone to progress to severe pneumonia, with fever, cough, and wheezing as the main clinical manifestations. A subset of cases progresses to critical illness, though the overall prognosis is favorable. Prolonged fever duration (>4.5 days), anorexia, and immune dysfunction were independent risk factors for critical illness.The risk prediction model constructed for pediatric critical HMPV infection demonstrated robust discriminative ability with excellent calibration.

The healing of the alveolar socket following tooth extraction is a complex process,which is influenced by multiple factors.After tooth extraction,the soft and hard tissues surrounding the extraction site undergo remodeling.During this process,systemic factors and local anatomical structure of the extraction site play a significant role.This review provides a detailed discussion of the alveolar socket healing process and its potential influencing factors.It aims to offer clinicians a comprehensive reference when assessing the healing potential of different extraction sites,thereby providing more informed and precise clinical decision-making.

Objective:To systematically retrieve and summarize the best available evidence on aerobic exercise combined with resistance training in stroke patients.Methods:Using a structured computer-assisted search strategy based on the "6S" model, literature was retrieved top-down from clinical decision support systems, guideline databases, professional society websites, evidence-based databases, and comprehensive databases. The search included literature related to aerobic and resistance training in stroke patients, including clinical decision tools, guidelines, recommended practices, evidence summaries, systematic reviews, expert consensus documents, and randomized controlled trials (RCT) . The search was performed from the inception of each database to February 28, 2025. Two researchers independently screened the literature, assessed quality, and extracted and synthesized the evidence.Results:A total of 21 publications were included: nine guidelines, three systematic reviews, one expert consensus, and eight RCTs. A total of 32 best evidence statements were summarized across 12 dimensions: timing of training initiation, training methods, training modes, intensity formulation strategies, training dosage, rest intervals, progression principles, progression strategies, training effects, individualized modifications, safety, and adherence management.Conclusions:This study systematically identified and summarized best-practice evidence for aerobic and resistance training in stroke patients. The findings provide strong evidence-based support for developing tailored and effective exercise interventions in stroke rehabilitation.

Objective:To investigate the clinical manifestations of medically refractory hereditary movement disorders in children and the efficacy of deep brain stimulation (DBS).Methods:A case series study.The clinical and follow-up data of 20 children with medically refractory hereditary movement disorders who underwent DBS treatment at the Neurology and Functional Neurosurgery Departments of Beijing Children′s Hospital, Capital Medical University, from July 2018 to April 2024, were retrospectively analyzed.The severity of movement disorder symptoms and surgical effects were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale Movement(BFMDRS-M) or the Unified Parkinson′s Disease Rating Scale Ⅲ(UPDRS Ⅲ).Results:There were 12 males and 8 females among the 20 children, with an onset age ranging from 4 months to 12 years and 5 months.Fourteen patients had hereditary dystonia, which is related to KMT2B in 11 patients, TOR1A in 2 patients and SGCE in 1 patient.Two patients had choreoathetosis, which is related to ADCY5-related familial movement disorders.Two patients had early-onset Parkinson′s disease, which is related to ATP6AP2 in 1 patient and VPS13C in 1 patient.Two patients had neurodevelopmental disorders with involuntary movements, which is related to GNAO1 in 1 patient, and the other patient was idiopathic.All the children were given oral Levodopa, Benzhexol, Baclofen, Tiapride Hydrochloride, Clonazepam alone or in combination.Three children showed obvious dyskinesia after Levodopa treatment.The symptoms of movement disorders in all children exhibited little to no improvement.Levetiracetam and Zonisamide had unstable effects in the treatment of myoclonia.DBS surgery was performed on all the patients aged from 3 to 16 years.Electrodes were successfully inserted into bilateral globus pallidus internus in 14 cases and bilateral subthalamic nuclei in 4 cases.The target was unknown in 2 cases.No surgery-related complications were observed.The patients were followed up for 3 months to 6 years, and the last follow-up age of the patients ranged from 5 years and 7 months to 22 years and 1 month.The rate of improvement in BFMDRS-M score was 37%-100% in 16 patients and >70% in 7 patients with hereditary dystonia.The rate of improvement in UPDRS Ⅲ score was 23% in 1 patient with VPS13C-related early-onset Parkinson′s disease. Conclusions:Childhood medically refractory hereditary movement disorders are a case series that exhibits significant phenotypic and genotypic heterogeneity.DBS surgery demonstrates significant efficacy for KMT2B-, TOR1A-, and SGCE-related hereditary movement disorders.