Objective : To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods : Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results : Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

Preeclampsia (PE) is a severe gestational disorder characterized by hypertension and proteinuria, with a subset of cases exhibiting an immune-driven phenotype marked by placental overexpression of proinflammatory cytokines and chronic inflammatory damage, profoundly impacting fetal development. To elucidate the pathophysiology of this PE subtype, we established an inflammation-driven PE mouse model via lipopolysaccharide (LPS) intraperitoneal injection, systematically evaluating histopathological changes in maternal heart, liver, lung, kidney, and placenta, and integrating transcriptomic profiling to uncover molecular mechanisms. LPS administration robustly induced maternal hypertension and proteinuria, hallmarks of PE, without significantly altering organ or fetal weights. Histological analyses revealed pronounced inflammatory damage in the maternal lung, kidney, and placenta, with the lung exhibiting the most severe pathology, characterized by inflammatory cell infiltration, alveolar wall thickening, and interstitial edema-challenging the conventional focus on placental and renal primacy in PE. Placental labyrinth and junctional zones displayed extensive structural disruption and necrosis, indicating functional impairment. Transcriptomic analysis identified 27 inflammation-related genes consistently upregulated across tissues, with protein-protein interaction networks pinpointing Il1β, Il6, Ccl5, Ccl2, Cxcl10, Tlr2, and Icam1 as hub genes. Quantitative PCR validation confirmed Tlr2 as a central regulator, evidenced by significant upregulation of Tlr2 in lung, kidney, and placenta of LPS-induced PE mice, while Cxcl10 exhibited placenta-specific upregulation, suggesting a synergistic inflammatory axis in placental pathology. These findings highlight the lung as a critical, yet underappreciated, target in inflammation-driven PE, reframe the multi-organ inflammatory landscape of the disease, and nominate Tlr2 and Cxcl10 as potential diagnostic biomarkers and therapeutic targets, offering new avenues for precision intervention in PE.
Animals ; Female ; Pregnancy ; Mice ; Pre-Eclampsia/genetics* ; Inflammation ; Lipopolysaccharides/adverse effects* ; Disease Models, Animal ; Transcriptome ; Placenta/pathology* ; Phenotype

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective : To investigate the therapeutic effects and underlying mechanisms of cannabidiol(CBD) and its nano-formulations on depression-like behaviors in mice. Methods : A murine model of acute anxiety and depression was established by intraperitoneal administration of lipopolysaccharide(LPS). A total of 55 mice were randomly assigned into several groups: for the long-term study, a control group(Con), a model group(LPS), a cannabidiol group(CBD), a nano-cannabidiol group(NCBD), and a sertraline(SER) group, each consisting of 7 mice. In the short-term study, mice were divided into four groups: the Con group, LPS group, CBD group, and NCBD group, with 5 mice in each group. Except for the Con group and LPS group, which were given distilled water, the remaining groups were administered 25 and 50 mg/kg of cannabidiol and its nano-formulationviaoral gavage. The open field and forced swimming tests were employed to assess anxiety-and depression-like behaviors inmice. Luxol Fast Blue myelin staining was employed to evaluate myelin sheath morphology in the prefrontal cortex, and immunofluorescence staining was utilized to quantify the protein expression levels of silencing information regulator(SIRT2), ionized calcium binding adaptor molecule-1(Iba-1), and interleukin-1β(IL-1β) in the prefrontal cortex. Results : In the long-term experiment, the LPS group exhibited a significant reduction in shuttle times(P<0.05), an increase in immobility time(P<0.01), and a decrease in the number and length of myelin sheaths(P<0.05) compared to the Con group. Compared to the LPS group, the depressive behaviors in the CBD, NCBD, and SER groups were significantly alleviated(P<0.01), and the number and length of myelin sheaths increased(P<0.05). In the short-term experiment, compared to the Con group, the LPS group exhibited significantly increased anxiety-and depression-like behaviors(P<0.05), downregulated SIRT2 expression(P<0.01), and upregulated Iba-1 and IL-1β expression(P<0.01). The CBD and NCBD groups demonstrated a reduction in anxiety and depression-like behaviors(P<0.05), an increase in SIRT2 expression(P<0.01), and a decrease in Iba-1 and IL-1β expressions(P<0.05) compared to the LPS group. Conclusion CBD and its nano-formulations effectively mitigate anxiety and depression-like behaviors in mice. The underlying mechanisms may be associated with the reversal of SIRT2 protein expression, demyelination changes, microglial activation, and the levels of inflammatory factors in the prefrontal cortex.

Objective To evaluate the efficacy of Compound Fipronil Spot-on Solution in repelling canine ticks.Methods A total of 140 dogs infested with ticks were randomly selected from regions in southern and northern China and assigned to four groups:southern test drug group,southern control drug group,northern test drug group,and northern control drug group.Each group comprised 35 dogs.Each dog was administered the prescribed dose.The number of ticks was counted on days 1,7,14,21,and 28 following the administration.The negative conversion and average reduction rates of the tick population were then subjected to statistical analyse.Results The mean efficacy of the test drug was 100%in both the southern and northern cohorts,28 days post-treatment.The control drug showed comparable efficacy,reaching a mean reduction of 100%in both regions by the same time point.No additional clinical manifestations or adverse events were observed across all treated dogs.Conclusions Compound Fipronil Spot-on Solutions effectively treats and prevents ticks in dogs in different regions of China.A single dose remains effective for up to 28 days,thus providing a convenient,effective solution.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective To evaluate the efficacy,safety and economics of romiplostim for treating primary immune thrombocytopenia(ITP)by rapid health technology assessment,and to provide an evidence-based basis for policy makers and clinical practice.Methods PubMed,Cochrane Library,Embase,CNKI,WanFang Data and VIP databases and the official websites of health technology assessment agency were electronically searched to collect high-quality clinical evidence and pharmacoeconomics evaluation literature of romiplostim for the treatment of ITP from inception to January 18,2024.Two researchers independently screened the literature,extracted information,and accessed the quality of included the literature,the extracted results were categorized and evaluated.Results A total of 14 literature were included,in which 8 systematic reviews/Meta-analysis and 6 pharmacoeconomic studies.In terms of efficacy,treatment with romiplostim significantly elevated platelet response rate,sustained platelet response rate,and mean platelet count in patients with ITP compared with placebo(P＜0.05).Romiplostim did not show a significant advantage in elevating patients'platelet response rate and sustained platelet response rate compared with other agents used to treat ITP(P＞0.05).In terms of safety,the incidence of serious adverse events was statistically lower with romiplostim compared to placebo(P＜0.05),while no significant differences were seen in the incidence of adverse events,bleeding events and thrombotic events(P＞0.05).There were no significant differences in the incidence of adverse events,serious adverse events,bleeding events,or thrombotic events when comparing romiplostim to other drugs for the treatment of ITP(P＞0.05).From an economic standpoint,most studies considered eltrombopag to be more economic advantages than romiplostim.Conclusion Romiplostim has good efficacy and safety in the treatment of ITP,and no advantage was shown in terms of economy.

Objective To investigate the therapeutic effect of transcutaneous auricular vagus nerve stimulation(taVNS)on overweight/obesity patients,and to explore its central mechanism.Methods Twenty-six overweight/obesity patients were randomly divided into two groups,12 cases in the taVNS test group(shortened as the taVNS group)and 14 cases in the lifestyle intervention control group(shortened as the control group).The patients in the control group were treated with online lifestyle intervention of calorie-restricted diet(CRD),and the patients in the taVNS group were treated with taVNS on the basis of the intervention for the control group.The taVNS was performed on unilateral acupoints of spleen and endocrine,twice(in the morning and at evening)per day,for five days a week.The treatment for the two groups covered four weeks.The obesity indicators such as body weight,body mass index(BMI)and waist circumference of the patients in the two groups were observed before and after treatment.Moreover,the resting-state cerebral functional magnetic resonance imaging(fMRI)data of the patients were collected after treatment,and then the regulatory effect of taVNS on the regional homogeneity(ReHo)of local cerebral area of the patients was observed.Results(1)During the trial,one case in each group dropped off,and a total of 24 patients(including 13 cases in the control group and 11 cases in the taVNS group)were finally included in the statistical analysis of the observation indicators.(2)After treatment,the body weight,BMI and waist circumference of patients in the taVNS group were decreased compared with those before treatment(P＜0.05),while the obesity indicators in the control group only showed a downward trend compared with those before treatment,the differences being not statistically significant(P＞0.05).The improvement of the obesity indicators of body weight,BMI,and waist circumference in the taVNS group was significantly superior to that in the control group,and there were statistically significant differences in the post-treatment indicators and in the pre-and post-treatment difference values of the indicators between the two groups(P＜0.05 or P＜0.01).(3)After treatment,the taVNS group had greater ReHo values in the left prefrontal lobe and medial frontal gyrus than the control group,and the control group had greater ReHo value in the right parietal lobe than the taVNS group,which indicated that compared with the control group,the ReHo of the left prefrontal lobe and medial frontal gyrus in the taVNS group was increased and the ReHo of the right parietal lobe was decreased(Pvoxel＜0.001,Pcluster＜0.05,corrected by FWE level).Conclusion As a non-invasive treatment method,taVNS exerts certain efficacy for the treatment of overweight/obesity patients.The central response mechanism for treatment of obesity is probably related with the modulation of taVNS on the functional areas of left prefrontal lobe,medial frontal gyrus,and right parietal lobe of the patients.

Health communication is the most core element in health education and health promotion.This paper summarizes and analyzes the research in China related to the evaluation of health communication effects through different media.It finds that the current evaluation indicators of communication effects are generally focused on changes in awareness rates.Traditional media and new media,as different types of communication mediums with their own advatages and limitations,do not have unified indicators to scientifically evaluate their communication effects in China,Due to the interdisciplinary nature of health communication,qualitative research methods(such as the Delphi method)have not been fully applied by researchers in the field of public health in China.This paper aims to sort out and compare various effects evaluation indicatorsof health communication with different media from current research through a literature review,and to provide evidences for improving a comprehensive and practical effect evaluation system of health communication in the future.