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 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.

Objective:To explore the effect of comfort nursing intervention in hospice care for advanced cancer patients at home, and to provide reference for hospice care for advanced cancer patients at home.Methods:A randomized controlled trial was conducted. A total of 105 patients with advanced cancer who were treated in the Cancer Hospital Affiliated to Harbin Medical University from January to February 2023 were selected as the research objects. According to the random number table, they were divided into control group of 53 cases and intervention group of 52 cases. The control group received routine nursing methods, while the intervention group received comfort nursing interventions on this basis. The intervention lasted for 4 weeks. The changes in palliative care outcomes, quality of life and death anxiety were compared between the two groups before and after intervention.Results:Totally 105 cases were included, 53 cases in the control group and 52 cases in the intervention group. In the control group, there were 25 males, 28 females, aged (58.96 ± 10.71) years old; in the intervention group, there were 22 males, 30 females, aged (59.82 ± 10.53) years old. Before intervention, there was no statistically significant difference in palliative care outcomes, quality of life and cancer death anxiety scores between the two groups of patients (all P>0.05). After intervention, the total score of palliative care outcomes in the intervention group was (13.34 ± 5.88) points, significantly lower than (16.15 ± 5.72) points in the control group, with a statistically significant difference ( t = 2.48, P<0.05). The overall health status score of quality of life was (68.55 ± 9.34) points in the intervention group, higher than (63.01 ± 9.28) points in the control group ( t = 3.05, P<0.05). The total score of cancer death anxiety was (8.85 ± 2.72) points, significantly lower than (10.59 ± 3.14) points of the control group, with a statistically significant difference ( t = 3.04, P<0.05). Conclusions:The application of comfort nursing mode in home based hospice care can improve the quality of hospice care for advanced cancer patients, reduce their level of death anxiety, and is of great significance for improving the quality of life of advanced cancer patients.

Objective To investigate the clinical and pathological features of adenoid basal cell carcinoma(ABC),adenoid cystic carcinoma(ACC),and basaloid squamous cell carcinoma(BSCC)with basaloid charac-teristics and improve the diagnostic and differential diagnostic ability of clinicians and pathologists for these lesions.Methods A retrospective study was conducted on the clinical and pathological data of 4 cases of ABC,1 case of ACC,and 3 cases of BSCC diagnosed and treated at Shenzhen Maternal and Child Health Hospital,Southern Medical University from April 2018 to December 2022.Pathological slides were reviewed and relevant literature was analyzed and summarized.Results All three types of tumors were common in postmenopausal women and were associated with high-risk HPV infection.ABC was a low-grade cancer and patients were often clinically asymp-tomatic.It was usually detected incidentally during cervical screening due to cytological abnormalities,or after cervical cone biopsy or hysterectomy for HSIL.It presented as superficial cervical infiltration and clinical staging was often early.ACC and BSCC were intermediate to high-grade cancers and they often presented with postmenopausal vaginal bleeding.A visible mass was observed on the cervix.The clinical staging was intermediate to advanced.The three types of lesions could coexist.Careful observation of the morphological characteristics and immunohistochemical staining could help with differential diagnosis.None of the 8 patients experienced recurrence or metastasis during follow-up.Conclusion Cervical ABC,ACC and BSCC are rare and they originate from reserve cells.They share the similarities in clinical and pathological morphology,but differ in treatment and prognosis.So,accurate differen-tiation among them has important clinical significance.

BACKGROUND:Abnormal activation of osteoclasts plays an important role in the bone destruction due to spinal tuberculosis.During the pathogenesis of osteoporosis,miR-155 knockdown activates adenosine phosphate-dependent protein kinase(AMPK)by increasing the expression of leptin receptors,thereby inhibiting osteoclast differentiation and bone resorption.However,the role of miR-155/leptin receptor(LEPR)/AMPK axis in the bone destruction due to spinal tuberculosis remains unclear. OBJECTIVE:To investigate the role and mechanism of miR-155/LEPR/AMPK axis in tuberculin-induced osteoclast formation. METHODS:RAW264.7 cells were cultured and treated with different concentrations of purified protein derivative(PPD)(1.0,2.5,5.0,10.0 IU/mL)and transfected with negative control(NC)sequence or miR-155 inhibitor,NC siRNA sequence or LEPR siRNA sequence.Tartrate resistant acid phosphatase staining was used to detect the number of osteoclasts.Fluorescence quantitative PCR was used to detect the expression of miR-155.Western blot was used to detect the expression of LEPR and p-AMPK.Double luciferase reporter gene was used to verify miR-155 targeting LEPR. RESULTS AND CONCLUSION:Compared with the control group,the number of osteoclasts and the expression level of miR-155 significantly increased,while the expression level of LEPR and p-AMPK significantly decreased in 2.5,5.0,and 10.0 IU/mL PPD groups(P＜0.05).Compared with NC+5.0 IU/mL PPD group,the number of osteoclasts and the expression level of miR-155 significantly decreased,while the expression level of LEPR and p-AMPK significantly increased in the miR-155 inhibitor+5.0 IU/mL PPD group(P＜0.05).Compared with the NC group,the fluorescence activity of LEPR wild-type double luciferase reporter gene was increased in the miR-155 inhibitor group,and decreased in the miR-155 mimic group(P＜0.05).Compared with si-NC+miR-155 inhibitor+5.0 IU/mL PPD group,the expression level of miR-155 had no significant change,the number of osteoclasts significantly increased,and the expression levels of LEPR and p-AMPL significantly decreased in si-LEPR+miR-155 inhibitor+5.0 IU/mL PPD group(P＜0.05).To conclude,tuberculin can induce osteoclast formation by increasing miR-155 expression and inhibiting downstream LEPR expression and AMPK activation.