Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

OBJECTIVE: To investigate the effect of miR-483-5p on hepatocellular carcinoma (HCC) cells proliferation and stemness, as well as the attenuating effect of Pien Tze Huang (PZH). METHODS: Differentially expressed miRNA between HepG2 cells and hepatic cancer stem-like cells (HCSCs) were identified by a miRNA microarray assay. miR-483-5p mimics were transfected into HepG2 cells to explore the effects of miR-483-5p on cell proliferation and stemness. HepG2 cells and HCSCs were treated with PZH (0, 0.25, 0.50 and 0.75 mg/mL) to explore the effects of PZH on the proliferation and stemness, both in non-induced state and the state induced by miR-483-5p mimics. RESULTS: miR-483-5p was significantly up-regulated in HCSCs and its overexpression increased cell proliferation and stemness in HepG2 cells (P<0.05). PZH not only significantly inhibited proliferation in HepG2 cells, but also significantly suppressed the cell proliferation and self-renewal of HCSCs (P<0.05). The effects of miR-483-5p mimics on proliferation and stemness of HepG2 cells were partially abolished by PZH. CONCLUSIONS miR-483-5p promotes proliferation and enhances stemness of HepG2 cells, which were attenuated by PZH, demonstrating that miR-483-5p is a potential molecular target for the treatment of HCC and provide experimental evidence to support clinical use of PZH for patients with HCC.
Humans ; MicroRNAs/metabolism* ; Cell Proliferation/drug effects* ; Liver Neoplasms/drug therapy* ; Carcinoma, Hepatocellular/drug therapy* ; Hep G2 Cells ; Neoplastic Stem Cells/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gene Expression Regulation, Neoplastic/drug effects*

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To explore the effects of different glucose concentrations on the synthesis and secretion of bone collagen in osteoblasts and the impact of diabetes on bone quality in mice.Methods(1)Primary osteoblasts were extracted from the skulls of neonatal mice via collagenase digestion and cultured in four groups under different glucose concentrations:normal glucose(5.5 mmol/L),moderate glucose(11.5 mmol/L),moderate-high glucose(16.5 mmol/L),and high glucose(25 mmol/L).EdU staining was performed to evaluate cell proliferation,while the Transwell assay was used to assess cell migration.Immunofluorescence and Western blotting were performed to detect and quantitatively analyze the content of type Ⅰ collagen(Col-1).Alizarin red S(ARS)staining and alkaline phosphatase(ALP)staining were applied to assess the effects of different glucose concentrations on osteogenic differentiation.(2)Six-week-old male C57BL/6 mice were randomly divided into control group and model group(5 in each group).The model group was fed a high-fat diet for 4 weeks followed by streptozotocin(STZ)injection to establish a diabetic mouse model.The osteogenic differentiation capacity of primary osteoblasts from both groups was assessed.(3)Micro-computed tomography(Micro-CT)was employed to analyze femoral bone mineral density(BMD),bone volume/tissue volume(BV/TV),trabecular number(Tb.N),and trabecular separation(Tb.Sp).Three-point bending test was conducted to evaluate mechanical parameters including maximum load,Young's modulus,fracture energy,and stiffness.RT-qPCR was employed to assess the expression of osteogenic differentiation genes(Alp,Opn,Col1a1,and Lox).Masson staining and Mallory staining were used to evaluate Col-1 content in trabecular bone.Results(1)EdU and Transwell assay results demonstrated that with the gradual increase in glucose concentration,the proliferation and migration abilities of osteoblasts were significantly decreased(P<0.001),and the protein expression levels of Col-1 and lysyl oxidase(LOX)were significantly reduced(P<0.01 or P<0.001).ARS and ALP staining revealed that calcium salt deposition and ALP activity in osteoblasts were significantly decreased with increasing glucose concentration(P<0.05 or P<0.001).(2)Compared with control group,mice in model group exhibited typical"three polies and one weight loss"symptoms(polyuria,polydipsia,polyphagia,and weight loss)of diabetes,and ARS and ALP staining showed a significant reduction in osteoblasts(P<0.001).(3)Micro-CT and three-point bending test results indicated that,compared with control group,mice in model group showed microarchitectural deterioration of bone,decreased Tb.N,increased Tb.Sp,and significantly reduced maximum load,Young's modulus,fracture energy,and stiffness(P<0.05).RT-qPCR results showed that the relative mRNA expression levels of osteogenic differentiation genes(Alp,Opn,Col1a1,and Lox)were significantly decreased in model group compared with control group(P<0.01 or P<0.001).Masson and Mallory staining indicated a significant reduction in collagen content in model group compared with control group(P<0.01).Conclusions High-glucose environment inhibits osteoblast proliferation,differentiation,and migration.Diabetic mice exhibit reduced bone quality and increased bone fragility,potentially mediated by decreased lysyl oxidase and collagen levels.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective:To explore effect of Yishen Paidu Formula on inflammatory response in chronic renal failure(CRF)rats and role of Calcineurin/nuclear factor of activated T cell(NFAT).Methods:CRF rat model was constructed,and randomly grouped into model group,low,medium and high doses Yishen Paidu Formula groups,with 10 rats in each group,another 10 rats were fed normally as a blank group;general situation of rats was recorded;urine protein quantification kit was applied to detect 24-hour urine protein level of CRF rats in each group;serum creatinine and urea nitrogen levels of CRF rats were detected;ELISA was applied to detect serum IL-1β,IL-6 and TNF-α levels in CRF rats;pathological changes of renal tissue were observed by HE staining;Western blot was applied to detect expressions of fibroblast growth factor 23(FGF23),Klotho protein,Calcineurin,NFAT protein in renal tissue of CRF rats in each group.Results:Compared with blank group,levels of creatinine,urea nitrogen in serum,24 h urine protein in urine,IL-1β,IL-6,TNF-α in serum,and protein levels of FGF23,Calcineurin,NFAT in kidney tissue were obviously increased in model group,level of Klotho protein was obviously decreased(P<0.05).Compared with model group,levels of creatinine,urea nitrogen in serum,24 h urine protein in urine,IL-1β,IL-6,TNF-α in serum,and protein levels of FGF23,Calcineurin,NFAT in kidney tissue were obviously decreased in low,medium and high doses Yishen Paidu Formula groups,level of Klotho protein was obviously increased,which were more significant with dosage increase(P<0.05).Conclusion:Yishen Paidu Formula may alleviate inflammatory response in CRF rats by inhibiting Calcineurin/NFAT signaling pathway.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore effect of Yishen Paidu Formula on inflammatory response in chronic renal failure(CRF)rats and role of Calcineurin/nuclear factor of activated T cell(NFAT).Methods:CRF rat model was constructed,and randomly grouped into model group,low,medium and high doses Yishen Paidu Formula groups,with 10 rats in each group,another 10 rats were fed normally as a blank group;general situation of rats was recorded;urine protein quantification kit was applied to detect 24-hour urine protein level of CRF rats in each group;serum creatinine and urea nitrogen levels of CRF rats were detected;ELISA was applied to detect serum IL-1β,IL-6 and TNF-α levels in CRF rats;pathological changes of renal tissue were observed by HE staining;Western blot was applied to detect expressions of fibroblast growth factor 23(FGF23),Klotho protein,Calcineurin,NFAT protein in renal tissue of CRF rats in each group.Results:Compared with blank group,levels of creatinine,urea nitrogen in serum,24 h urine protein in urine,IL-1β,IL-6,TNF-α in serum,and protein levels of FGF23,Calcineurin,NFAT in kidney tissue were obviously increased in model group,level of Klotho protein was obviously decreased(P<0.05).Compared with model group,levels of creatinine,urea nitrogen in serum,24 h urine protein in urine,IL-1β,IL-6,TNF-α in serum,and protein levels of FGF23,Calcineurin,NFAT in kidney tissue were obviously decreased in low,medium and high doses Yishen Paidu Formula groups,level of Klotho protein was obviously increased,which were more significant with dosage increase(P<0.05).Conclusion:Yishen Paidu Formula may alleviate inflammatory response in CRF rats by inhibiting Calcineurin/NFAT signaling pathway.