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.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To investigate the efficacy and safety of combination regimen containing daratumumab in multiple myeloma (MM) patients. METHODS: The clinical data of 14 newly diagnosed MM patients and 58 relapsed refractory MM patients treated with combination regimen containing daratumumab from November 2020 to March 2023 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. The efficacy and safety of combination regimen were analyzed. RESULTS: The median age of the 72 patients was 62 (38-78) years, including 35 males and 37 females. The overall response rate (ORR) of patients receiving first-line, second-line, and third-line or above treatment was 92.9% (13/14), 68.2% (30/44), and 42.9% (6/14), respectively. The median progression-free survival (PFS) was not reached, 15.4 months, and 9.7 months in three groups, respectively (all P <0.05), while the median overall survival (OS) was all not reached. Among relapsed refractory patients, the ORR of those treated with DVd, DPd and DRd regimen was 50.0% (12/24), 40.0% (4/10) and 100% (10/10), the median PFS was 2.8 months, 10.3 months and not reached, and the median OS was 15.4 months, not reached and not reached, respectively. Furthermore, the PFS and OS in the DRd group were superior to those in the other two groups (all P <0.05). Cox univariate and multivariate analysis showed that lactate dehydrogenase (LDH) ≥250 U/L and extramedullary disease were independent adverse prognostic factors for PFS, and LDH ≥250 U/L was also an independent adverse prognostic factor for OS. Hematologic adverse reactions were mainly lymphopenia (87.5%) and thrombocytopenia (52.8%), while non-hematologic adverse reactions were mainly infusion-related reactions (19.4%) and infections (11.1%). CONCLUSIONS The combination regimens containing daratumumab can be used as first-line treatment for patients with newly diagnosed MM. In patients with relapsed refractory MM, early use of regimens containing daratumumab may improve treatment response rate and prolong PFS. The DRd regimen has better therapeutic response and survival advantages. LDH is an independent prognostic factor affecting PFS and OS in MM patients.
Humans ; Multiple Myeloma/drug therapy* ; Middle Aged ; Aged ; Male ; Female ; Antibodies, Monoclonal/administration & dosage* ; Adult ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.