Children， as a special group， frequently experience of off-label drug use worldwide. Common reasons for off-label drug use in children include the lack of data on pediatric patients during the clinical trial stage of drug development， delayed updates to drug instructions， and the non-standard professional behavior of some doctors. Off-label drug use in children is a double-edged sword. It could save lives and provide a way to explore additional functions of drugs， while it may also lead to the phenomenon of hyper-indication abuse， increasing the risk of adverse drug events. Regulating off-label drug use in children can safeguard the best treatment rights and interests of children. It is recommended to encourage pharmaceutical enterprises to conduct research and development of pediatric new drugs， simplify the approval process for drug instructions amendments， accumulate evidence-based medical evidence for off-label drug use in children， standardize the process of off-label drug use in children in medical institutions， continuously improve the standardized diagnosis and treatment capabilities of pediatricians， and actively cooperate with the families of pediatric patients in diagnosis and treatment， so as to comprehensively safeguard the rights and interests of both doctors and patients.

Purpose: Gold-standard urodynamic examination is widely used in the diagnosis and treatment of lower urinary tract dysfunction. The purpose of urodynamic quality control is to standardize urodynamic examination and ensure its clinical reference value. In our study, we attempted to use a deep learning (DL) algorithm model, mainly for the recognition of typical urodynamic signal, to help physicians complete high-quality urodynamic examinations. Methods: Urodynamic image data from 2 cohorts of adult patients with neurogenic bladder were used: (1) 300 patients with neurogenic bladder in our center from 2012 to 2018 (1,960 images used to train and validate the DL model); and (2) 100 patients with neurogenic bladder from 2020 to 2021 (695 images used to test the performance of the DL model). This resulted in a total of 2,655 images to train, validate and test the DL algorithm to predict the urdynamic signals. Results: Yolov5l had the best detection performance and the highest comprehensive index score (F1, 0.81; mean average precision, 0.83). Our study is a retrospective single-center study, and the generalization ability of the model has not been verified. Conclusions DL algorithms can help operators identify typical urodynamic signals in real time, improve the interpretation and quality of urodynamic examination, and benefit patients.

Purpose: Gold-standard urodynamic examination is widely used in the diagnosis and treatment of lower urinary tract dysfunction. The purpose of urodynamic quality control is to standardize urodynamic examination and ensure its clinical reference value. In our study, we attempted to use a deep learning (DL) algorithm model, mainly for the recognition of typical urodynamic signal, to help physicians complete high-quality urodynamic examinations. Methods: Urodynamic image data from 2 cohorts of adult patients with neurogenic bladder were used: (1) 300 patients with neurogenic bladder in our center from 2012 to 2018 (1,960 images used to train and validate the DL model); and (2) 100 patients with neurogenic bladder from 2020 to 2021 (695 images used to test the performance of the DL model). This resulted in a total of 2,655 images to train, validate and test the DL algorithm to predict the urdynamic signals. Results: Yolov5l had the best detection performance and the highest comprehensive index score (F1, 0.81; mean average precision, 0.83). Our study is a retrospective single-center study, and the generalization ability of the model has not been verified. Conclusions DL algorithms can help operators identify typical urodynamic signals in real time, improve the interpretation and quality of urodynamic examination, and benefit patients.

Purpose: Gold-standard urodynamic examination is widely used in the diagnosis and treatment of lower urinary tract dysfunction. The purpose of urodynamic quality control is to standardize urodynamic examination and ensure its clinical reference value. In our study, we attempted to use a deep learning (DL) algorithm model, mainly for the recognition of typical urodynamic signal, to help physicians complete high-quality urodynamic examinations. Methods: Urodynamic image data from 2 cohorts of adult patients with neurogenic bladder were used: (1) 300 patients with neurogenic bladder in our center from 2012 to 2018 (1,960 images used to train and validate the DL model); and (2) 100 patients with neurogenic bladder from 2020 to 2021 (695 images used to test the performance of the DL model). This resulted in a total of 2,655 images to train, validate and test the DL algorithm to predict the urdynamic signals. Results: Yolov5l had the best detection performance and the highest comprehensive index score (F1, 0.81; mean average precision, 0.83). Our study is a retrospective single-center study, and the generalization ability of the model has not been verified. Conclusions DL algorithms can help operators identify typical urodynamic signals in real time, improve the interpretation and quality of urodynamic examination, and benefit patients.

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Objective:To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association.Methods:In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups.Results:A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio ( HR)=1.16, 95% CI: 1.06-1.27], a 12% higher risk of ischemic stroke ( HR=1.12, 95% CI: 1.01-1.24), and a 39% higher risk of hemorrhagic stroke ( HR=1.39, 95% CI: 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion:Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Euglycemic diabetic ketoacidosis(euDKA)is a rare acute metabolic disorder syndrome,its characteristics include metabolic acidosis with a high anion gap,positive ketones in blood or urine,and blood glucose＜13.9 mmol/L.Due to low blood sugar level,euDKA is easy to be missed or delayed treatment in clinical work,resulting in serious consequences.In recent years,many cases of euDKA have been reported,but its inducements and pathogenesis are not fully understood.This article reviews the common inducements and pathogenesis of euDKA.