Objective To apply the World Health Organization(WHO)International Classification of Functioning,Disability and Health(ICF)to a comprehensive analysis of the functional characteristics of children with attention deficit hyper-activity disorder(ADHD)and to develop a functionally oriented,individualized exercise rehabilitation protocol. Methods International Classification of Diseases(ICD-11)and ICF were utilized to systematically analyze the body structure,physical function,activities and participation,and environmental factors of children with ADHD.Based on the ICF's bio-psycho-social model of function,disability and health,combined with the theory of somat-ic and mental interaction,and referring to the WHO 2020 Guidelines on Physical Activity and Sedentary Behav-iour,particularly the sections relevant to disabled adolescents,a function-oriented exercise rehabilitation protocol suitable for children with ADHD was formulated. Results The dysfunctions of children with ADHD were mainly manifested in the area of mental functions(b1),which was highlighted by attention functions(b140),energy and drive functions(b130)and higher-level cognitive func-tions(b164).In terms of activities and participation,limitations were primarily observed in learning and applying knowledge(d1),general tasks and demands(d2),communication(d3),and interpersonal interactions and relation-ships(d7).In addition,environmental factors such as products and technology(e1),support and relationships(e3),and attitudes(e4)affected the progression of the disorder.According to the guidelines,physical activity could be categorised into motor skill-based activities,fitness-based activities and sport-based activities.Children with ADHD were recommended to perform at least 60 minutes of moderate to high intensity fitness activities(e.g.,aerobic exercise)and motor skill activities(e.g.,basic movement exercises)a day,and at least three times a week of high intensity activities such as strength/resistance training and athletic competitions.The protocol should also ensure an accessible environment and adaptive assistive technology to promote the overall functional rehabilitation of children with ADHD. Conclusion Based on the ICF theoretical framework,combined with the theory of mind-body interaction,and with refer-ence to the WHO 2020 Guidelines on Physical Activity and Sedentary Behaviour,a functionally oriented exercise rehabilitation protocol was constructed,focusing on the children's attentional function,learning and mental func-tions.

Objective:To compare the localization accuracy of interictal 18F-FDG and 18F-flumazenil (FMZ) PET/CT imaging for focal cortical dysplasia (FCD). Methods:A retrospective analysis was conducted on 22 patients (12 males, 10 females; age 8-36 years) with pathologically confirmed FCD who underwent surgical resection at Huashan Hospital, Fudan University from July 2021 to June 2023. All patients underwent 18F-FDG and 18F-FMZ PET/CT scans before surgery. Surgical pathological diagnosis was used as the gold standard. Visual scoring was used to analyze the images. The accuracy of the two imaging methods in the localization of FCD was compared, and subgroup analysis (FCD Ⅱa, FCD Ⅱb) of different pathological type was further performed. Paired- t test, χ2 test or Fisher′s exact test was used to analyze the data. Results:The visual score of 18F-FMZ PET/CT was higher than that of 18F-FDG (3.00±0.82 vs 2.27±0.92; t=4.17, P=0.020). The accuracy of interictal 18F-FMZ PET/CT was 77.27%(17/22), which was higher than that of 18F-FDG PET/CT (36.36%, 8/22; χ2=7.50, P=0.006). Subgroup analysis showed that within the cohort of patients diagnosed with FCD Ⅱa ( n=18), 18F-FMZ PET/CT outperformed 18F-FDG in terms of accuracy for localization (15/18 vs 6/18; P=0.006). Conclusion:Compared to 18F-FDG, 18F-FMZ PET/CT demonstrates clearer and more accurate identification of lesion borders, and exhibits higher precision, which provides valuable guidance for preoperative localization.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Autophagic flux refers to a series of dynamic process of autophagic bilayer membrane formation, autophagosome formation, autophagolysosomes formation and degradation. The etiology of cataract is complex, including congenital abnormalities in lens development due to genetic mutations, oxidative damage due to aging, abnormalities in glucose metabolism due to diabetes, and proliferation of lens epithelial cells(LECs)stimulated by postoperative inflammatory factor, all of which are associated with the development of cataracts. A growing number of research in recent years have discovered that altering the status of LECs can contribute to the pathophysiological process of cataract by regulating autophagic flux. This review summarized the impacts of autophagic flux regulation on cataract.

Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes, and multi-target drugs provide a promising therapy idea for the treatment of cancer. Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs. In this paper, 50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database, and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time. Through the multi-target anti-cancer prediction system, some dominant fragments that act on multiple tumor-related targets were analyzed, which could be helpful in designing multi-target anti-cancer drugs. Anti-cancer traditional Chinese medicine (TCM) and its natural products were collected to form a TCM formula-based natural products library, and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system. As a result, alkaloids, flavonoids and terpenoids were predicted to act on multiple tumor-related targets. The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments. In conclusion, the multi-target anti-cancer prediction system is very effective and reliable, and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs. The anti-cancer natural compounds found in this paper will lay important information for further study.
Antineoplastic Agents/pharmacology* ; Bayes Theorem ; Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; Neoplasms/drug therapy*

ObjectiveTo establish a population pharmacokinetic （PPK） model of teicoplanin in septic patients from Intensive Care Unit （ICU） and to explore its pharmacokinetic characteristics and related covariates. MethodsThe study included 66 septic patients hospitalized in the department of critical care medicine from November 2017 to February 2020. After intravenous dosing of teicoplanin in septic patients， the trough concentration of teicoplanin was determined by high performance liquid chromatography （HPLC） and the concentration-time data was analyzed by non-linear mixed effect model. The pharmacokinetic parameters and residual errors were evaluated. The influence of covariates on model parameters was tested by forward addition and backward elimination. The predictive performance of the final model was assessed by internal validation. ResultsA two-compartment model best described the teicoplanin concentration-time data. The PPK parameter estimates were central clearance of 0.45 L/min， peripheral clearance of 0.72 L/min， central volume of distribution of 39.74 L and peripheral volume of distribution of 152.41 L. Creatinine， total protein， and lactate were found to significantly affect central clearance of teicoplanin （P<0.05）. ConclusionThe two-compartment PPK model of teicoplanin established in this study could be used for individualized treatment in septic patients from ICU due to its good stability and high predictive accuracy.

OBJECTIVE: To investigate the combined anti-inflammatory effect of activating blood circulation and detoxifying Chinese medicines in unstable angina (UA) patients. METHODS: This study was an open-labeled, randomized controlled trial conducted in 5 centers in Beijing. A total of 154 patients were randomized into two groups at a 1:1 ratio by random numbers. Based on the conventional treatment, patients in the activating blood circulation (ABC) group were treated with Guanxin Danshen Droping Pill (, 0.4 g, thrice daily), and patients in the activating blood circulation and detoxifying (ABCD) group were treated with Guanxin Danshen Droping Pill (0.4 g, thrice daily) and Andrographis tablet (0.2 g, thrice daily) for 4 weeks. The primary outcome was the serum level of high sensitive C reaction protein (hs-CRP), and the secondary outcome index included the serum levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble CD40 ligand (sCD40L), thrombomodulin (TM), the score of angina pectoris, the score of blood stasis syndrome, and the score of Chinese medicine symptoms, observed at week 0 and week 4. RESULTS: A total of 144 patients completed the trial (ABC group, n=70; ABCD group, n=74). There were no significant differences in the clinical baseline characteristics between the two groups. When compared with the ABC group, ABCD group showed better performance in reducing the level of inflammatory factors, especially hs-CRP (P<0.05), IL-6 (P<0.01) and TNF-α (P<0.01). In term of clinical symptoms, ABCD group played a better role in improving the scores of angina pectoris and blood stasis syndrome than ABC group (all P<0.05). CONCLUSIONS The combination of Guanxin Danshen Dropping Pill and Andrographis tablet exert significant anti-inflammatory effect on UA patients, which is superior to single Guanxin Danshen Dropping Pill. (Registration No. ChiCTR-TRC-13004072).
Angina Pectoris/drug therapy* ; Angina, Unstable/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; China ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Percutaneous Coronary Intervention

Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.
Aconitum ; Gene Expression Profiling ; Genes, Plant/genetics* ; Real-Time Polymerase Chain Reaction ; Reference Standards ; Reverse Transcriptase Polymerase Chain Reaction

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method:BALB/c mice were randomly divided into six groups according to their weight grade： normal group， HCoV-229E infection group， cold and damp group， a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome， and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar （0.128，0.064 g·kg^-1） was administrated by gavage for 3 days from the day of infection. The observation indexes included： general state observation of mice， inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in the lung tissues of mice. Serum levels of motilin（MTL）， gastrin （GAS）， and cytokines interleukin（IL）-10，IL-6， tumor necrosis factor-α（TNF-α）and interferon-γ（IFN-γ） in lung tissue of mice were determined by enzyme-linked immunosorbent assay（ELISA）. The percentages of CD4⁺ T lymphocytes，CD8⁺ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group， model group mice lung index increased significantly （P<0.01）， nucleic acids significantly increased expression of lung tissue in mice （P<0.01）， significantly higher serum MTL content in mice， GAS content significantly decreased （P<0.05，P<0.01）， lung tissue cells in the immune factor TNF-α， IL-10 and IL-6 were significantly increased （P<0.01）， peripheral blood lymphocyte CD4⁺ T cells in mice， The percentages of CD8⁺ T cells and B cells were significantly decreased （P<0.01）. Compared with model group， in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower （P<0.01）， the lung tissue of mice express nucleic acid decreased significantly （P<0.01）， MTL content decreased significantly （P<0.01）， the lung tissue of mice in the IL-6， IL-10， the TNF-α， IFN-γ levels were significantly lower （P<0.01）， in vitro cultivation bezoar high dose group can significantly increase the CD4⁺ T cell percentage （P<0.05）， in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation， pulmonary interstitial edema， as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice， improving the pathological damage of the lung tissue， adjusting the immune effective and inhibiting the clearing of inflammatory factors， and to provide a laboratory basis for clinical medication.

Isopentenyl diphosphate isomerase (IDI) is a key enzyme in the regulation of triterpenes biosynthesis and plays an important role in ginsenoside biosynthesis. In this study, two IDI genes, PvfIDI1 (GenBank No. MZ736417) and PvfIDI2 (GenBank No. MZ736418) were cloned from Panax vietnamensis var. fuscidiscus. The open reading frame of both PvfIDI1 and PvfIDI2 was 924 bp encoding 307 amino acids. The molecular weights of PvfIDI1 and PvfIDI2 were 34.84 kDa and 34.66 kDa, respectively, with theoretical pIs of 6.01 and 5.66. Bioinformatic analysis indicated that PvfIDI1 and PvfIDI2 contained two conserved sequences: TNTCCSHPL and WGEHELDY. Phylogenetic analysis showed that PvfIDI1 and PvfIDI2 were closely related to Panax notoginseng IDI. Expression analysis showed that both PvfIDI1 and PvfIDI2 genes are expressed in root, rhizome, stem and leaf of P. vietnamensis var. fuscidiscus. However, PvfIDI1 is highly expressed in the rhizome and PvfIDI2 is highly expressed in the stem. PvfIDI1 and PvfIDI2 recombinant proteins were expressed in E. coli; a functional coloration experiment showed that PvfIDI1 and PvfIDI2 could promote the accumulation of lycopene, indicating that both PvfIDI1 and PvfIDI2 encode functional IDI enzymes. The cloning and functional studies on PvfIDI1 and PvfIDI2 provide a foundation for the further study of IDI and the regulation of ginsenoside biosynthesis in P. vietnamensis var. fuscidiscus.