Attention deficit and hyperactive disorder （ADHD） is the most common neurodevelopmental disorder of childhood. It seriously impairs academic achievement， social interaction， and vocational development， and increases the risk of accidental injury and substance abuse. In some cases， the symptoms may also exert an indirect disruptive effect on public order. Its aetiology involves interactions among genetic， perinatal environmental， and psychosocial factors that cannot be fully disentangled by single clinical studies. Therefore， a systematic evaluation of existing animal models is essential for revealing pathophysiology and developing novel therapies. Using the keywords "attention deficit and hyperactive disorder"， "models， animal"， "validity"， and their English equivalents， we systematically searched PubMed， Web of Science， CNKI， and Wanfang for publications from 2000 to 2025 （retrieving 328 publications） and added further references by citation tracking. Eighty-six rodent ADHD models that provided detailed construction protocols， behavioural assessments， neurobiological mechanisms， or pharmacological data were included and classified into spontaneous genetic， genetically engineered， and environmentally induced paradigms. Their face， construct， and predictive validity were compared. Among spontaneous genetic models， spontaneously hypertensive rats reproduce hyperactivity， impulsivity， and stimulant responses well， yet hypertension and sex differences limit specificity. Acallosal mouse strains link corpus callosum absence to ADHD-like behaviours， but neurotransmitter studies remain scarce. Genetically engineered rodents—including dopamine transporter， neurokinin-1 receptor and mediator complex subunit 23 knockout or conditional gene knockout lines—precisely dissect dopaminergic， noradrenergic， synaptic， or epigenetic pathways， yet generally lack full phenotypic coverage， social-deficit modelling， and comorbidity representation， and are accompanied by adverse effects such as growth retardation or ocular defects. Environmentally induced models employ lead， polychlorinated biphenyls， alcohol， nicotine exposures， 6-hydroxydopamine lesions， neonatal hypoxia， early social isolation， or maternal stress to recapitulate core symptoms. However， dose-schedule standardisation is lacking. Behavioural reversibility diverges from clinical persistence， and non-specific phenotypes such as anxiety or depression are common. Overall， no single paradigm simultaneously achieves high validity across all three dimensions. Currently， ADHD models have progressed from single-factor simulations to multidimensional evaluation， yet significant gaps remain in genetic-background standardisation， sex differences， cross-species translation， and syndrome-differentiation modelling under traditional Chinese medicine. Future directions should integrate genetic， environmental， and epigenetic interactions， establish life-span validation systems， and incorporate computational neuroscience alongside integrative Chinese-Western strategies to enhance clinical relevance and translational utility， thereby providing robust evidence-based support for mechanistic elucidation， drug screening and precision intervention in ADHD.

The linear ubiquitin chain assembly complex (LUBAC), composed of heme-oxidized IRP2 ubiquitin ligase 1-interacting protein (HOIP), haem-oxidized IRP2 ubiquitin ligase-1(HOIL-1), and SHANK-associated RBCK1 homology-domain-interacting protein (SHARPIN), and its specific deubiquitinating enzyme OTULIN, regulates the dynamic balance of Met1-linked linear ubiquitination and maintains ubiquitin signaling homeostasis. Their precise interaction plays a central role in the regulation of nuclear factor-κB (NF-κB) and type I interferon signaling, inflammatory response, and cell survival and death. Dysregulation of the LUBAC-OTULIN axis can lead to aberrant immune and inflammatory signaling, immunodeficiency, and dysregulation of receptor-interacting protein kinase 1-mediated apoptosis or necroptosis. Genetic defects in OTULIN and LUBAC are associated with rare autoinflammatory diseases such as OTULIN-related autoinflammatory syndrome (ORAS) and HOIP/HOIL-1/SHARPIN deficiency, respectively, with complex clinical phenotypes and gene dose correlation. Current treatments primarily rely on glucocorticoids and tumor necrosis factor inhibitors, and hematopoietic stem cell transplantation has shown potential curative value in some patients with severe ORAS. This review summarizes the molecular composition, interaction mechanisms, and pathogenic roles of the LUBAC-OTULIN axis in rare autoinflammatory diseases, providing reference for the development of targeted therapeutic strategies.

Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid–induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Objective:To develop the Motivation for Bedtime Procrastination Questionnaire for College Students(CS-MBPQ)and evaluate its validity and reliability.Methods:Based on literature analysis,interviews with severe bedtime procrastinators,and open-ended surveys with college students,the initial questionnaire was formed.A total of 389 college students were recruited to conduct item analysis and exploratory factor analysis.Additionally,691 college students were selected for confirmatory factor analysis,criterion validity testing,and internal consistency reliability analysis,and 132 of them were retested two weeks later.The subscale of behav-ioral intention from the Theory of Planned Behavior Questionnaire(TPBQ),Bedtime Procrastination Scale(BPS),and a self-made question for the frequency of bedtime procrastination were used as criterion tools.Results:The CS-MBPQ consists of 10 items,encompassing three factors:emotional need,external influence,and behavioral attitude,explaining 63.31％of the variance.Confirmatory factor analysis indicated that the three-factor structure model of CS-MBPQ fitted well(x2/df=4.90,RMSEA=0.07,CFI=0.96,TLI=0.94).The CS-MBPQ total scores and scores for each factor were positively associated with the score of intentions to sleep on time,BPS scores,and bed-time procrastination frequency(ICC=0.14-0.53,Ps＜0.05).The internal consistency reliabilities for CS-MBPQ and the three factors were 0.87,0.89,0.74,and 0.66,respectively,and the test-retest reliabilities(ICC)were 0.74,0.66,0.69,and 0.58,respectively.Conclusion:The Motivation for Bedtime Procrastination Questionnaire for College Students(CS-MBPQ)demonstrates good validity and reliability,which could be used as a tool to evaluate motivations for bedtime procrastination among Chinese college students.

Objective To investigate the requirement of blood sugar management in elderly patients with Type Ⅱ diabetes and to provide a reference for development of a program in management of blood sugar.Methods Using interpretive decriptive phenomenological research,an interview outline based on the theoretical domain framework was developed and face-to-face semi-structured interviews were conducted with 16 aged patients who had Type Ⅱ diabetes in the Department of Endocrinology and Metabolism of a Grade ⅢA hospital in Jiangxi Province.The participants were selected by purposive sampling.Colaizzi 7-step analytical method,in conjunction with Nvivo 11 software,was used to analyse,summarise and extract the themes.Results Seven themes related to the theoretical domain framework were extracted,which included knowledge,skills,environmental context and resources,behavioural adjustment,motivation and goals,emotions and self-efficacy.After refinement,nine sub-themes on major requirement for blood glucose management were extracted,which included the requirements for knowledge and skills in blood sugar management,support from the community and healthcare resources,support from the family,changes in maladaptive behaviours,individualised blood sugar management,motivation for self-management,clarity in goals of blood sugar control,emotional support and psychological adjustment,and support for strengthened beliefs(9 sub-themes).Conclusion Elderly patients with Type Ⅱ diabetes have diverse and individualised needs in management of blood sugar.In the future,healthcare staff should develop appropriate strategies or programs to meet the individual needs of patients by addressing the actual needs of patients,improving the self-management behaviours of patients so as to improve the effects of the blood sugar control.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:To explore the effect of Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) with chemotherapy on breast cancer patients who got agranulocytosis of 3 to 4 degree, agranulocytosis with fever (FN) and the influential factors of relative dose intensity (RDI) chemotherapy scheme. Meantime, the value of CD34 + and CD45 in peripheral blood on predicting agranulocytosis of 3-4 degree were investigated.Methods:A total of 104 women with breast cancer were treated at Huzhou Maternal and Child Health Hospital and Cancer Hospital of Zhejiang Province from Jan. 2022 to Sep. 2023. All subjects received primary prevention with PEG-rhG-CSF during chemotherapy. The clinical risk factors of agranulocytosis, FN and RDI were analyzed. The levels of CD34 + and CD45 in peripheral blood samples were analyzed by flow cytometry. Then the predictive value of the receiver characteristic curve (ROC) for Grade 3 to 4 agranulocytosis after primary prophylaxis with PEG-rhG-CSF for breast cancer chemotherapy was evaluated.Results:Among 104 breast cancer patients who received primary prevention of PEG-rhG-CSF during chemotherapy, 28 patients had agranulocytosis of 3 to 4 grade, 10 patients got FN, and 12 patients developed RDI<85%. The results of single factor analysis showed that CD34 +, CD45 and chemotherapy scheme were the influential factors of agranulocytosis of 3 to 4 degree, and low RDI of chemotherapy scheme ( OR=0.584, OR=0.999, OR=2.299, OR=0.100, OR=0.999, OR=3.088, P<0.05) . It also showed that CD34 + and chemotherapy scheme were the influential factors of FN ( OR=0.099, OR=2.667, P<0.05) . Multivariate Logistic regression analysis showed that CD34 +, CD45 and intensive chemotherapy were the independent risk factors of agranulocytosis of 3 to 4 degree after primary prevention with PEG-rhG-CSF ( OR=0.602, OR=0.999, OR=20.174, P<0.05) . CD34 + and intensive chemotherapy scheme were the independent influential factors of FN and RDI of chemotherapy scheme after primary prevention with PEG-RHG-CSF ( OR=0.072, OR=33.934, OR=0.086, OR=54.788, P<0.05) . The area under the curve (AUC) of CD34 + were 0.767 (95% CI:0.659-0.876) , AUC of CD45 were 0.743 (95% CI:0.644-0.842) , and the AUC of combined two indexes was 0.825 (95% CI:0.730-0.920) , which was higher than that of single index. So AUC of CD34 + and CD45 can be used for predicting agranulocytosis of grade 3 to 4 in breast cancer patients receiving primary prophylaxis with PEG-rhG-CSF. Conclusions:The levels of CD34 + and CD45 in peripheral blood of breast cancer patients with agranulocytosis of grade 3 to 4 receiving primary prevention with PEG-rhG-CSF during chemotherapy are lower. Combined detection of CD34 + and CD45 in peripheral blood can predict the occurrence of agranulocytosis of grade 3 to 4 in breast cancer patients after primary prevention with PEG-rhG-CSF. Also it can provide a reliable basis for assessing the risk of grade 3 to 4 agranulocytosis.

Objective:To explore the differences in semen parameters and the embryo outcomes in assisted reproductive technology between infertile patients with different levels of polyzoospermia and normal sperm con-centration,focusing on the relationship between polyzoospermia and sperm nucleoprotein maturity.Methods:A total of 212 couples with polyzoospermia(concentration ≥ 125 × 106/ml)who were admitted to the Insititute of Women,Children and Reproductive Health for infertility from October 12,2020 to August 25,2022 were selected.According to the concentration range,108 couples were divided into polyzoospermia group A[concentration(125-＜250)× 106ml]and 104 couples were divided into polyzoospermia group B(concentration ≥250 × 106/ml).Another 119 infertile couples with normal sperm concentration[(20-80)× 106/ml]were selected as the control group.The difference of semen parameters among the 3 groups male patient was compared,and the cor-relation between sperm concentration and the proportion of nucleoprotein-immature sperm was analyzed.The em-bryo development and pregnancy outcomes were compared between the 3 groups of women who received in vitro fertilization using intracytoplasmic sperm injection(ICSI).Results:①The age,days of abstinence,sperm concen-tration,total number of motile spermatozoa,total number of spermatozoa,total number of progressive spermato-zoa,and proportion of nuclear protein immature spermatozoa were all higher in group A and group B male patient of polyspermia compared to the control group,while the semen volume was lower compared to the control group(P＜0.01).The results of correlation analysis showed a positive correlation between sperm concentration and the proportion of nuclear protein immature spermatozoa(r=0.240,P=0.000).②The rate of diprokaryotic fertilization(2PN)was reduced after assisted reproduction in group A and group B with polyzoospermia,among which the rate of polyzoospermia in group B was lower than that in control group(P＜0.05),and the clinical pregnancy rate was lower than that in control group(51.2％vs.69.3％),and the biochemical pregnancy rate was higher than that in control group(9.3％vs.1.3％,P＜0.05).Conclusions:The total number of progressive spermatozoa and motile spermatozoa was higher in polyzoospermia patients than control group,but the nuclear protein imma-ture of spermatozoa was significantly higher than that in control group.When the sperm concentration exceeded 125 × 106/ml,the 2PN rate decreased,and when the sperm concentration exceeded 250 × 106/ml,the clinical pregnancy rate decreased significantly.Interventions should be taken before the implementation of ART to reduce the negative effects of high sperm concentration.

Objective To investigate the effect of joint of Zishen Anshen Tang and growth hormone on the clinical outcomes of in vitro fertilization embryo transfer(IVF-ET)in patients with decreased ovarian reserve function(DOR).Methods A clinical trial was conducted on 108 DOR patients who underwent IVF-ET at the Reproductive Center of from January 2023 to August 2024.They were randomly assigned to a control group and a experimental group,each with 54.The control group was given growth hormone(GH),while the experimental group was additionally given Zishen Anshen Tang.The ovulation induction status,trigger day hormone levels,egg retrieval and embryo development,and clinical outcomes were compared.Results The duration of gonadotropin(Gn)use showed no great difference between two groups(P>0.05).The experimental group had lower Gn dosage,early LH peak rate,and luteinizing hormone(LH),higher estradiol(E2),progesterone(P),egg retrieval,2PN fertilization,available embryos,number of high-quality embryos on day 3,blastocyst formation rate,clinical pregnancy rate,and cumulative pregnancy rate,and a lower cycle cancellation rate than control group(P<0.05).Conclusion The joint of Zishen Anshen Tang and growth hormone for IVF-ET in DOR patients can improve their sex hormone and have a positive impact on clinical outcomes.