To investigate the clinical characteristics and prognosis of extracranial malignant rhabdoid tumor (eMRT) in children, and to provide a reference for the clinical treatment of this disease.

Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

“Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner’s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.

In this study,the similarities and differences of plasma collection and quality control in China and abroad were analyzed by comparing the related regulations,standards,guidelines and literatures.Rational and constructive suggestions were proposed,aiming to optimize domestic plasma management and promote the improvement of plasma-related standards.There was little difference on facilities and safety control process of plasma between China and the developed countries(United States,EU and Japan),However,significant differences existed on plasma station setting,donor screening standards,collection interval,volume limits,plasma testing modes and tests,plasma quarantine standard and utilization of recovered plasma.The United States sets the industry benchmark and is worthy of reference for our country both in plasma collection and quality control.

AIM To investigate the effects of Shuyu Pills combined with evolimus on the epithelial mesenchymal transformation of triple negative breast cancer cells 4T1 and MDA-MB-231 induced by TGF-β1.METHODS The 4T1 and MDA-MB-231 cells were divided into the blank group and the induction group to induce the epithelial mesenchymal transformation with TGF-β1 cytokine treatment,followed by the assignment into the model group,the Shuyu Pills group,the everolimus group and the Shuyu Pills combined with everolimus group.CCK8 method,plate cloning method,cell scratch test and Transewll test were used to detect the proliferation,cloning formation,migration and invasion ability of the cells whose expressions of E-cadherin,N-cadherin,Vimentin,MMP9,MMP2 and pathway proteins PTEN,PI3K,Akt and mTOR were detected by Western blot.RESULTS Compared with the blank group,the induction group displayed a cell morphological change from epithelioid to stromal,decreased expression of E-cadherin protein(P＜0.01);and increased protein expressions of N-cadherin and Vimentin(P＜0.05).Compared with the model group,each group intervened with the medicine displayed decreased proliferation,clone formation,migration and invasion ability of both kinds of cells(P＜0.01);increased protein expressions of PTEN and E-cadherin(P＜0.05,P＜0.01);and decreased protein expressions of PI3K,Akt,mTOR,N-cadherin,Vimentin,MMP9 and MMP2(P＜0.05,P＜0.01);and more significantly in the Shuyu Pills combined with evolimus group(P＜0.05,P＜0.01).CONCLUSION With a more ideal effect than the single uses in inhibiting the TGF-β1-induced epithelial mesenchymal transformation of triple-negative breast cancer cells,the combination use of Shuyu Pills and everolimus may work through the regulation of PI3K/Akt/mTOR signaling pathway.

Objective To investigate the efficacy of cannabidiol(CBD)in improving renal function and protecting the kidney in mice with unilateral ureteral obstruction(UUO).Methods A total of 24 healthy,8-week-old,WTC57BL/6 male mice were divided into the Sham group,UUO group and UUO+CBD group,with 8 rats in each group.The UUO models were established by ligating one side of the ureter and removing the contralateral kidney to ensure unilateral kidney hydronephrosis.In the UUO+CBD group,5 mg/kg CBD was intraperitoneally injected immediately after the operation,once a day for 10 days.The Sham and UUO groups were given the same amount of normal saline.Blood sample was collected through the inner canthus venous plexus of the orbit 24 hours after the last administration.The levels of serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),superoxide dismutase(SOD),and malondialdehyde(MDA)were detected with an automatic biochemistry analyzer.The histopathological sections were prepared,the pathological changes of renal tissues were observed under a light microscope,and the pathological injuries were scored.Mitochondrial quantity and morphological structure changes were observed with a transmission electron microscopy.Results Compared with the Sham group,the UUO group exhibited significantly higher levels of Scr[(22.55±3.29)μmol/L vs.(12.11±3.32)μmol/L],BUN[(18.62±2.15)mmol/L vs.(10.05±1.19)mmol/L],TNF-α[(21.04±2.56)pg/mL vs.(9.26±0.47)pg/mL],IL-1β[(10.25±1.25)pg/mL vs.(5.44±0.99)pg/mL],and MDA[(31.26±1.17)nmol/mL vs.(17.12±1.39)nmol/mL],but significantly lower level of SOD[(90.26±2.11)U/mL vs.(136.54±3.05)U/mL],all P＜0.000 1.Compared with the UUO group,the UUO+CBD group showed a significant decrease in the levels of Scr[(16.82±0.89)μmol/L vs.(22.55±3.29)μmol/L],BUN[(14.35±0.99)mmol/L vs.(18.62±2.15)mmol/L],TNF-α[(16.29±0.88)pg/mL vs.(21.04±2.56)pg/mL],IL-1β[(6.23±0.95)pg/mL vs.(10.25±1.25)pg/mL],MDA[(20.36±1.23)nmol/mL vs.(31.26±1.17)nmol/mL],and renal pathological damage score[(1.88±0.64)vs.(2.50±0.76)],but a significant increase in SOD level[(117.84±1.57)U/mL vs.(90.26±2.11)U/mL],all P＜0.000 1.Under electron microscopy,mitochondrial swelling,loss of inner membrane structure,and membrane rupture were observed in the UUO group,while the UUO+CBD group showed milder morphological changes.Conclusion CBD improves renal function in UUO model mice through anti-inflammatory,antioxidant and mitochondrial protection,and is a potential therapeutic drug for renal protection in clinic.

Objective To investigate the relationship between C-reactive protein(C-RP)/albumin ratio(CAR)and peripheral artery disease(PAD)in elderly patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 elderly patients with T2DM hospitalized in the Department of Endocrinology of our hospital were enrolled in this study from December 2022 to December 2023 and divided into PAD group with ankle brachial index(ABI)≤0.9(n=78)and T2DM group with ABI>0.9(n=72).The general data,biochemical indicators and CAR were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between CAR and each biochemical index.Logistic regression analysis was used to explore the influencing factors for PAD in T2DM patients.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of CAR for PAD.Results Age,DM duration,body mass index,systolic blood pressure,diastolic blood pressure,C-RP,white blood cell count,fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),blood uric acid,low density lipoprotein cholesterol(LDL-C),and blood urea nitrogen(BUN),CAR was higher(P<0.05),while albumin,high density lipoprotein cholesterol(HDL-C),and ABI were lower in the PAD group than in the T2DM group(P<0.05).Pearson correlation analysis showed that CAR was positively correlated with FPG,TG,and BUN(P<0.05),and negatively correlated with HDL-C and ABI(P<0.05).Logistic regression analysis showed that CAR(OR 1.594,95%CI 1.236～2.062),TC(OR 1.070,95%CI 1.017～1.130),TG(OR 1.101,95%CI 1.021～1.184),HDL-C(OR 0.883,95%CI 0.813～0.965),LDL-C(OR 1.090,95%CI 1.012～1.186),FPG(OR 1.065,95%CI 1.020～1.104)were influencing factors for the occurrence of PAD in elderly patients with T2DM.ROC curve analysis showed that the area under the curve of CAR was 0.82 for predicting PAD in elderly patients with T2DM,the cut-off value was 0.35,the sensitivity was 78%,and the specificity was 85%.Conclusions CAR is correlated with ABI in elderly patients with T2DM.Given CAR is an influencing factor for the occurrence of PAD,it may serve as a potential predictor for PAD development in this population.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.