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.

ObjectiveTo investigate the effect of Dingzhi Xiaowan （DZXW） in post-stroke cognitive impairment （PSCI） model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group， model group， low-dose DZXW group （1.43 g·kg^-1）， and high-dose DZXW group （2.56 g·kg^-1）， with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage， and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein （APP）， amyloid 42 （Aβ₄₂）， acetylcholinesterase （AChE）， and superoxide dismutase （SOD） were measured by enzyme-linked immunosorbent assay （ELISA）. Deoxyribonucleotide end transferase-mediated nick end labelling （TUNEL） assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor 1-alpha （HIF-1α）， B-cell lymphoma 2 （Bcl-2） homologous structural domain protein （Beclin1）， sequestosome 1 （p62）， microtubule-associated protein light chain 3 （LC3）， Bcl-2， and Bcl-2-associated X protein （Bax） in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly increased in the model group （P<0.01）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly decreased （P<0.01）. Compared with the model group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity rate， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups （P<0.05）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly higher （P<0.05）. ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Acute kidney injury(AKI)is characterized by high morbidity,high mortality,high disability rate and high treatment cost,its pathological mechanism has not been fully elucidated and there is a lack of ef-fective treatment methods.Klotho,a kidney-specific protective protein,is mainly expressed in renal tubular ep-ithelial cells,regulates the AKI progression and mitigates the renal injury through multiple pathways,inclu-ding the regulation of the renin-angiotensin-aldosterone system(RAAS),antioxidant stress,anti-inflamma-tion,modulation of cell death and anti-fibrotic effects.At present,the Klotho-based strategies for AKI preven-tion and treatment remain in the preclinical stage,requiring further investigation.This article reviews the mo-lecular regulatory mechanisms of Klotho in AKI and its diagnostic and therapeutic potential,aiming to provide new idea for the pathological mechanisms and clinical translation of AKI.

Objective To explore the feasibility of automatic segmentation of clinical target volume(CTV)and organs at risk(OARs)for cervical cancer using AccuLearning(AL)based on geometric and dosimetric indices.Methods Seventy-five CT localization images with manual contouring data of postoperative cervical cancer were enrolled in this study.Sixty cases were randomly selected to trained to generate automatic segmentation model by AL,and the CTV and OARs of the remaining 15 cases were automatically contoured.Radiotherapy plans on the automatic segmentation contours were imported on the CT images of manual contours.The efficiency,Dice similarity coefficient(DSC),Hausdorff distance(HD)and dosimetric parameters were compared between the two methods.Results The time of automatic segmentation was significantly shorter than that of the manual contour(P<0.05).The DSC of all structures were≥0.87.The HD of bowel bag and rectum were about 10 mm,and that of the rest of OARs were less than 5 mm.CTV(D98,V90% ,V95% ,Dmean,HI),bowel bag(V50)and bladder(V50)had significant differences in dosimetric comparison(P<0.05).Conclusion The automatic segmentation model based on AL can improve the efficiency of radiotherapy.Automatic segmentation of OARs has the potential of clinical application,while that of CTV still needs to be further modified.

Objective To explore the correlation between intestinal dose and acute radiation enteritis(ARE)in patients with cervical cancer received concurrent chemoradiotherapy,and optimize the dose limit of intestinal tissue.Methods 158 cervical cancer patients received concurrent chemoradiotherapy from 2014 to 2019 were selected in this study.According to CTCAE 5.0,patients with ARE≥grade 2 were classified as ARE≥grade 2 group,otherwise classified as ARE0.7,P<0.05).Conclusions For patients with cervical cancer received concurrent chemoradiotherapy,the dose of bowelbag V5 and V40 should be considered to rationally optimize the dose of bowelbag in the radiotherapy plan,so as to reduce the incidence of ARE≥grade 2.

Objective:To evaluate the effect of pre-infusion of hypertonic saline on the postoperative cognitive function in elderly patients.Methods:This was a prospective study. Seventy-six patients of both sexes, aged≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, who underwent elective shoulder arthroscopic surgery under brachial plexus block combined with general anesthesia from June 2022 to January 2023 in our hospital, were selected and divided into 2 groups ( n=38 each) by the random number table method: hypertonic saline group and normal saline group. At 30 min before anesthesia induction, 3% hypertonic saline of 4 ml/kg was intravenously infused in hypertonic saline group, and normal saline 4 ml/kg was intravenously infused in normal saline group. The occurrence of intraoperative cerebral desaturation events was recorded. Venous blood samples were collected at 24 h postoperatively, and the plasma concentrations of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha and S-100β were measured by enzyme-linked immunosorbent assay, and the expression of neutrophil CD11b was detected by flow cytometry. Rey auditory verbal learning test, trail making test, digit symbol substitution test, and stroop color-word test were performed at 1 day before surgery and 5 days after surgery, and the postoperative cognitive dysfunction was assessed using the Z-score method. Results:Compared with normal saline group, the concentrations of plasma IL-6, tumor necrosis factor-alpha and S-100β and expression of neutrophil CD11b were significantly decreased in hypertonic saline group, and the incidence of cognitive dysfunction and cerebral desaturation events was decreased in hypertonic saline group ( P<0.05). Conclusions:Pre-infusion of hypertonic saline can reduce inflammatory responses and improve postoperative cognitive function in elderly patients.

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system, seriously threatening the health and development of human beings. AD pathogenesis is related to amyloid β-protein accumulation, microtubule-associated protein Tau accumulation and hyperphosphorylation in the brain. C-abl kinase can affect signal pathways related to Aβ and Tau proteins, promote neuroinflammatory response and respond to oxidative stress signals; and its overexpression can lead to neuronal damage, resulting in clinical manifestations such as cognitive and memory decline. This paper reviews the relationship between c-abl kinase and AD pathogenesis, and feasibility and limitations of c-abl kinase inhibitors in AD, in order to provide new ideas for AD treatment.

Objective To assess the feasibility of utilizing the ExacTracDynamic surface monitoring system(ETD)for setup and body surface monitoring in patients with thoracic tumors undergoing intensity-modulated radio-therapy(IMRT).Methods Patients receiving IMRT for thoracic tumors were included in this study.The enrolled patients were alternatively assigned to either conventional cross curve positioning(control group)or surface monitoring system-assisted positioning(experimental group).ETD X-ray images were utilized for calibration purposes prior to radiotherapy,enabling the determination of setup errors.A region of interest(ROI)was delineated on the body surface above the sternum,and real-time body surface monitoring was performed based on this ROI during radiotherapy.Post-radiotherapy X-ray images were obtained to verify patient position.Data regarding left-right(X),head-foot(Y),abdomen-back(Z),pitch,roll,and yaw directions were recorded and analyzed.Results A total of 60 patients were enrolled,with 754 fractions of radiotherapy in the control group and 718 fractions in the experimental group.The setup errors in the X and Z directions were significantly smaller in the experimental group compared to the control group(P<0.05).Moreover,there was a significant reduction in the number of setup errors≤0.50 cm for X,Y,and Z directions,as well as≤1.00° for Roll angle in the experimental group compared to the control group(P<0.05).Additionally,differences were observed between surface monitoring and X-ray image verification regarding position deviation along Y and Z directions(P<0.05),although these deviations remained within submillimeter levels on average.Conclusion Surface monitoring system-assisted positioning can enhance radiotherapy setup accuracy among thoracic tumor patients,particularly along X and Z directions.Furthermore,when setting ROI above sternum on body surface area,surface monitoring provides better reflection of target area's position deviation.

Objective To survey the levels and distributed status of serum vitamin D in children in Hanzhong city of Shaanxi,and provide a basis for the prevention of children with vitamin D deficiency.Methods A total of 6 780 children aged 1 to 6 years from March 2019 to February 2021 in Children's Health Clinic of Hanzhong Center Hospital for physical examination were selected as subjects.The levels of serum 25-hydroxyvitamin D[25(OH)D],serum 25-hydroxyvitamin D2[25(OH)D2]and serum 25-hydroxyvitamin D3[25(OH)D3]were measured by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the factors of ages and sexes and seasons were analyzed.Results The levels of serum 25(OH)D,25(OH)D2 and 25(OH)D3 in all children were 38.24±9.84 ng/ml,2.31±3.91 ng/ml and 35.93±9.93 ng/ml,respectively.The vitamin D deficiency rate,insufficiency rate and adequacy rate were 2.75％(186/6 780),18.29％(1 240/6 780)and 78.96％(5 354/6 780),respectively.The levels of serum 25(OH)D and 25(OH)D3 in children aged 1～2,2～3 and 3～6 years were gradually decreased with the growth of age,while the rate of vitamin D deficiency was increased,with significant differences(F=1 153.499,1 165.341,1 374.051,all P＜0.05).There were no significant differences in distributed status of serum of vitamin D and the levels of serum 25(OH)D,25(OH)D2 and 25(OH)D3 levels among different genders(t/x2=0.727,1.271,0.222,2.659,all P＞0.05).The levels of serum 25(OH)D and 25(OH)D3 in winter were lower than those in spring,summer and autumn,and the differences were statistically significant(q=6.853,7.281,6.801;5.341,6.225,5.989,all P＜0.01).The vitamin D deficiency rate in winter was higher than that in spring,summer and autumn(6.60％,2.64％,1.91％,1.66％).and the differences were statistically significant(x2=31.733,52.252,57.756,all P＜0.01).Conclusion A high incidence of vitamin D deficiency or insufficiency was found in children aged 3 to 6 in Hanzhong city.It was necessary to strengthen outdoor activities in winter,encourage monitoring of serum vitamin D levels,and supplement vitamin D if necessary.