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

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.

OBJECTIVE To investigate the effect of pachymic acid （PA） on renal function and fibrosis in chronic renal failure （CRF） rats and its potential mechanism based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. METHODS Using male SD rats as subjects， the CRF model was established by 5/6 nephrectomy； the successfully modeled rats were divided into model group， PA low-dose， medium-dose and high-dose groups （5， 10， 20 mg/kg PA）， high-dose PA+ROCK pathway activator lysophosphatidic acid （LPA） group （20 mg/kg PA+1 mg/kg LPA）， with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein， once a day， for 12 consecutive weeks. During the experiment， the general condition of rats was observed in each group. After the last administration， the serum renal function indexes （blood urea nitrogen， serum creatinine， uric acid） of rats in each group were detected， the renal histopathological changes were observed； the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] and inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6）， the positive expression rates of connective tissue growth factor （CTGF） and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins （RhoA， ROCK1） and fibrosis- related proteins （transforming growth factor-β1， bare corneum homologs 2， α-smooth muscle actin） were determined. RESULTS Compared with the sham operation group， the rats in model group had reduced diet， smaller body size， listless spirit and sluggish response， reduced and atrophied glomeruli， dilated renal tubules with chaotic structure， and a large number of inflammatory cells infiltrated interstitium； the serum levels of renal function indexes， renal tubule injury score， renal fibrosis area proportion， the levels of MDA and inflammatory factors， the positive expression rates of CTGF and collagen Ⅰ， and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased， while SOD level was significantly decreased （P＜0.05）. Compared with the model group， the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees，and the above quantitative indexes were significantly improved in a dose-dependent manner （P＜0.05）. LPA could significantly reverse the improvement effect of PA on the above indicators （P＜0.05）. CONCLUSIONS PA can improve renal function and alleviate renal fibrosis in CRF rats， which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.

OBJECTIVE To investigate the effect and mechanism of Astragalus polysaccharide （APS） on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis （PD）. METHODS Rats were randomly divided into normal control group （Control group）， model group （PD group）， 70 mg/kg APS group （APS-L group）， 140 mg/kg APS group （APS-H group）， and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α （HIF-1α） agonist DMOG group （APS-H+DMOG group）， with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， the peritoneal ultrafiltration （UF）， mass transfer of glucose （MTG）， the levels of serum creatinine （Scr） and blood urea nitrogen （BUN） were detected in rats； peritoneal histomorphology and peritoneal fibrosis （peritoneal thickness and proportion of collagen fiber deposition） were observed； the microvascular density and the expression levels of α-smooth muscle actin （α-SMA）， laminin （LN）， HIF-1α and vascular endothelial growth factor （VEGF） proteins were detected in peritoneal tissue of rats. RESULTS Compared with Control group， the mesothelium of rats in the PD group was loosely arranged and shed， inflammatory cells infiltrated， the peritoneal thickness and proportion of collagen fiber deposition were increased significantly （P＜0.05）. The levels of MTG， Scr and BUN in serum， microvascular density and the expressions of α-SMA， LN， HIF-1α and VEGF proteins were significantly increased， while the level of UF was significantly decreased （P＜ 0.05）； compared with PD group， the levels of above indexes were significantly reversed in APS-L and APS-H groups （P＜0.05）， and the improvement of APS-H group was better than APS-L group （P＜0.05）. Compared with APS-H group， the levels of above indexes in APS-H+DMOG group were all reversed （P＜0.05）. CONCLUSIONS APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.

This work was aimed at predicting and verifying B-cell epitopes of SARS-CoV-2 E protein through bioinformatics methods,and clarifying the dominant B cell epitopes with mouse polyclonal antibody serum prepared through SARS-CoV-2 re-combinant E protein immunization and human positive serum vaccinated with inactivated SARS-CoV-2 vaccine.The structural and B-cell linear epitopes of SARS-CoV-2 E protein were predicted with SOPMA,Expasy,SWISS-MODEL,IEDB database,and Bepid-2.0 software.Candidate epitopes were expressed as GST-tagged recombinant protein fragments in an E.coli sys-tem,and their immunoreactivity with mouse and human poly-clonal positive serum against SARS-CoV-2 E protein was de-tected by western blotting and indirect ELISA,respectively.The epitope prediction results showed that E protein contained linear B cell epitopes Ser6-Val14 and Tyr57-Pro71,and the conformational epitopes of Glu8-Val12,Leu39-Tyr59,and Ser60-Leu65.The GST tagged recombinant E protein fragments of E1 and E3,containing Ser6-Val14 and Tyr57-Pro71 epitopes,respectively,as well as E2 without an epitope sequence as a control,were expressed in an E.coli expression system and successfully purified with an Ni-NTA column.Western blotting and indirect ELISA analysis indicated that all mouse and human SARS-CoV-2 positive sera positively reacted with only E1 and E3 proteins,but negatively reacted with E2 protein,thus indicating that the corresponding epitope prediction with Ser6-Val14 and Tyr57-Pro71 was correct.This study successfully predicted and preliminarily identified two linear B cell epitopes of SARS-CoV-2 E protein,thus providing a reference for the preparation of new coronavirus vaccines and the analysis of immune response characteristics.

Developing geriatric department is an important measure to address the aging population. In recent years, there had been some progress in the construction of geriatric departments in hospitals of China, but there was still significant room for improvement in the context of rapid aging. At present, the geriatric departments in hospitals were mainly facing problems and difficulties such as low attention within the hospital, shortage of geriatric medical professionals, imperfect payment systems, inapplicable performance evaluation indicators, and low social awareness. This study suggested that we should further strengthen the construction of geriatric departments in hospitals, accelerate the construction of geriatric medicine talent teams, promote the reform of payment methods related to geriatric medicine services, optimize the performance evaluation methods of geriatric medicine departments, and enhance the social identity of geriatric medicine departments, so as to provide references for promoting the sustainable and high-quality development of geriatric medicine departments in hospitals of China.

Nowadays,with the continuous deepening and development of vocational education teaching reform,medical higher vocational education always takes moral education as the fundamental task.As an independent type of education,vocational education should always deepen the integration of industry and education and the integration of science and education.Through the teaching research of"problem chain+course ideological and political case",this study innovates the coordinated education team of drug nursing curriculum,the collaborative education method and the collaborative education evaluation,and improves the teaching effect.