ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Objective To investigate the clinical manifestations and prognosis of patients with anti-leucine rich glioma inactivated 1（LGI1）antibody encephalitis. Methods A retrospective analysis was performed for the data of patients with anti-LGI1 antibody encephalitis who were hospitalized in Department of Neurology，Xuanwu Hospital，Capital Medical University，from September 2019 to December 2023，including clinical features，treatment，and prognosis. Results A total of 80 patients were enrolled，including 48 male patients and 32 female patients. Of all 80 patients，51（63.8%）had the initial symptom of epilepsy，13（16.3%）had the initial symptom of faciobrachial dystonic seizures，26（32.5%）had the initial symptom of cognitive impairment，and 12（15%）had the initial symptom of mental and behavioral disorders. As for comorbidities，there were 28 patients（35%）with hyponatremia，22（27.5%）with Hashimoto's thyroiditis，and 5（6.25%）with tumor. All 80 patients tested positive for serum LGI1 antibody，and 69（86.3%）tested positive for LGI1 antibody in cerebrospinal fluid. Among the 80 patients，37（46.25%）had abnormalities on magnetic resonance imaging，and 30 had abnormalities on 18F-FDG PET/CT. There were 50 patients with abnormalities on video electroencephalography. A total of 77 patients received first-line immunotherapy，and after follow-up for 1 year，19.4% of the patients had the sequela of seizure，59.7% of the patients had deterioration of the memory，and 48.6% of the patients had mental and behavioral disorders. Conclusion Epilepsy，cognitive impairment，and mental and behavior disorders are the most common manifestations of anti-LGI1 antibody encephalitis. There is generally a good prognosis after immunotherapy，with the sequelae of cognitive impairment and mental and behavioral disorders.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

BACKGROUND: Acupuncture therapy provides a complementary and alternative approach to treating major depressive disorder (MDD), but its efficacy and safety have still not been comprehensively assessed. Recently published systematic reviews remain confusing and inconclusive. OBJECTIVE: This systematic review evaluated the efficacy and safety of acupuncture therapy alone or combined with antidepressants for adult patients with mild and moderate MDD. SEARCH STRATEGY: Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, PubMed, Embase, and Cochrane Library were searched from their inceptions to March 2025. INCLUSION CRITERIA: Randomized controlled trials that compared acupuncture therapy with antidepressants, or acupuncture therapy plus antidepressants with acupuncture therapy or antidepressants for adult patients with mild and moderate MDD were included. DATA EXTRACTION AND ANALYSIS: Five reviewers independently extracted data from original literature using a standardized form, and the data were verified by two reviewers to ensure accuracy. Statistical meta-analyses, publication bias analyses, and subgroup analyses were performed by using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. RESULTS: A total of 60 eligible studies including 4675 participants were included. Low-certainty evidence showed that compared with antidepressants, acupuncture therapy (standardized mean difference [SMD] = -0.57; 95% confidence interval [CI] = [-0.87, -0.27]; I² = 86%; P = 0.006) or acupuncture therapy plus antidepressants (SMD = -1.00; 95% CI = [-1.18, -0.81]; I² = 77%; P < 0.00001) may reduce the severity of depression at the end of treatment. Low-certainty evidence indicated that compared with acupuncture therapy alone, acupuncture therapy plus antidepressants slightly reduced the severity of depression at the end of treatment (SMD = -0.38; 95% CI = [-0.61, -0.14]; I² = 18%; P = 0.002). Similar results were also found for acupuncture's relief of insomnia. The reported adverse effects of acupuncture therapy were mild and transient. For most of the subgroup analyses, acupuncture type, scale type, and the course of treatment did not show a significant relative effect. CONCLUSION Acupuncture therapy may provide antidepressant effects and relieve insomnia with mild adverse effects for adult patients with mild and moderate MDD. But the certainty of evidence was very low. More high-quality, well designed, large-scale studies with long-term follow-up are needed in the future. Please cite this article as: Kuang HJ, Yang HS, Feng YX, Tang H, Fan Q, Xu YQ, Cui S, Musil R, Luxenburger H, Zhang YX, Zhao H, Zhang YQ. Efficacy and safety of acupuncture therapies for adult patients with mild and moderate major depressive disorder: A systematic review and meta-analysis. J Integr Med. 2025; 23(5):471-491.
Humans ; Acupuncture Therapy/methods* ; Depressive Disorder, Major/therapy* ; Adult ; Antidepressive Agents/therapeutic use* ; Treatment Outcome ; Randomized Controlled Trials as Topic

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides (MOIG) on bone loss of rheumatoid arthritis (RA) rats, and the mechanism of osteoclast function and activity induced by lipopolysaccharide (LPS). RA rats were established by injecting bovin type II collagen. The Bio-ethic Committee of Zhejiang Chinese Medical University approved all experimental protocols associated with this study (IACUC-20180410-03). The collagen-induced arthritis (CIA) rats were administered drug by gavage for 8 weeks; the femoral trabecular micro-structure changes were observed in CIA rats by micro-CT; the LPS-induced osteoclasts model further observed the effect and mechanism of anti-inflammatory osteoporosis in vitro. The results indicated that MOIG could markedly increase bone mineral density (BMD) in CIA rats, improve trabecular micro-structure. In vitro studies demonstrated that MOIG could significantly inhibit osteoclastogensis and differentiation, suppress tartrate resistant acid phosphatase (TRAP) activity, F-actin ring formation, TNF receptor associated factor 6 (TRAF6) recruitment, and inhibitor of nuclear factor kappa-Bα (IκBα) degradation as well as p65 phosphorylation, thereby repressing nuclear factor kappa-B (NF-κB) signaling pathway activation. Subsequently, MOIG effectively inhibited osteoclast nuclear factor of activated T-cells c1 (NFATc1) and cellular oncogene Fos (c-Fos) expression, as well as bone resorption related protein activity including matrix metalloprotein 9 (MMP-9) and cathepsin K (CtsK). Meanwhile, MOIG also repressed the phosphorylation expression of Janus activating kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), thereby inhibiting JAK2/STAT3 signaling pathway activation. Moreover, further studies found that MOIG could suppress glycogen synthase kinase-3β (GSK-3β) activity, and GSK-3β gene silencing could markedly inhibit oetsoclast F-actin ring formation as well as the phosphorylation expression of p65 and STAT3. Of note, compared with GSK-3β gene silencing group, there was no significant difference in the group treated with both MOIG with GSK-3β gene silencing simultaneously. Thus, the results suggested that MOIG may inhibit NF-κB signaling pathway and JAK2/STAT3 signaling pathway activation via regulating GSK-3β, thereby alleviating bone destruction in RA.

Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.

Objective:To investigate the risk factors and cumulative risk of myopia in children and adolescents, providing a basis for identifying cumulative risk factors in preventing and controlling myopia.Methods:Baseline data from the mental and physical health cohort of children and adolescents established in Inner Mongolia Autonomous Region were used. A stratified random cluster sampling method was adopted to select 138 974 students from fourth to twelfth grade as participants. Distance visual exams, refractive assessments, and questionnaires were conducted on the included students. Logistic regression analysis was used to evaluate each risk factor's impact on myopia's prevalence. The number of risk factors was summed to form a cumulative risk score, and logistic regression analysis was conducted to examine the association between the cumulative risk score and the prevalence of myopia. Additionally, the association between the cumulative risk score of myopic students and their degree of refractivity was analyzed using a generalized estimating equation.Results:The study found a high prevalence of myopia among children and adolescents at baseline (70.2%). Girls exhibited a higher prevalence (74.8%) than boys (65.6%), urban areas (74.3%) surpassed suburban ones (68.6%), and the incidence was greater in high schools (80.3%) compared to middle schools (75.3%), which, in turn, was higher than in elementary schools (57.7%) (all P<0.05). Analysis of risk factors revealed that children and adolescents experiencing improper reading and writing distances ( OR=1.10, 95% CI: 1.07-1.13), excessive homework ( OR=1.09, 95% CI: 1.06-1.12), insufficient sleep ( OR=1.10, 95% CI: 1.07-1.13), having myopic father ( OR=1.98, 95% CI: 1.91-2.05), having myopic mother ( OR=2.04, 95% CI: 1.97-2.10), or using classroom chairs not matched to their height faced ( OR=1.04, 95% CI: 1.01-1.07) increased myopia risks. Additionally, the prevalence and significant odds ratio of myopia increased with the increase in cumulative risk score, with every additional unit of cumulative risk score increasing the right eye's refractive error by -0.10 D. Conclusion:The presence of multiple factors and their comprehensive score increases the prevalence of myopia in children and adolescents.

Background::Given the established genetic linkage between triggering receptors expressed on myeloid cells 2 (TREM2) and Alzheimer’s disease (AD), an expanding research body has delved into the intricate role of TREM2 within the AD context. However, a conflicting landscape of outcomes has emerged from both in vivo and in vitro investigations. This study aimed to elucidate the multifaceted nuances and gain a clearer comprehension of the role of TREM2. Methods::PubMed database was searched spanning from its inception to January 2022. The search criteria took the form of ( "Alzheimer’s disease" OR "AD" ) AND ( "transgenic mice model" OR "transgenic mouse model" ) AND ( "Triggering receptor expressed on myeloid cells" OR "TREM2" ). Inclusion criteria consisted of the following: (1) publication of original studies in English; (2) utilization of transgenic mouse models for AD research; and (3) reports addressing the subject of TREM2.Results::A total of 43 eligible articles were identified. Our analysis addresses four pivotal queries concerning the interrelation of TREM2 with microglial function, Aβ accumulation, tau pathology, and inflammatory processes. However, the diverse inquiries posed yielded inconsistent responses. Nevertheless, the inconsistent roles of TREM2 within these AD mouse models potentially hinge upon factors such as age, sex, brain region, model type, and detection methodologies.Conclusions::This review substantiates the evolving understanding of TREM2’s disease progression-dependent impacts. Furthermore, it reviews the interplay between TREM2 and its effects across diverse tissues and temporal stages.