Alzheimer's disease (AD) is the commonest neurodegenerative disease that causes memory decline, cognitive dysfunction and behavior disorders in the aged people. Primary pathological hallmarks of AD include amyloid-β (Aβ), neurofibrillary tangles (NFTs), gliosis, and neuronal loss. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have important physiological functions, especially in aspects of controlling the resting membrane potential, pacemaker activity, memory formation, sleep and arousal. This article reviews the structure, distribution, regulation of HCN channels and the role of HCN channels in the pathological mechanisms of AD, aiming to provide drug therapeutic targets for the prevention and treatment of AD.
Humans ; Alzheimer Disease/physiopathology* ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/physiology* ; Animals ; Amyloid beta-Peptides/metabolism*

This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

Gegen Qinlian Decoction(GQD) is a classic prescription for the clinical treatment of ulcerative colitis(UC). This study, based on the differences in efficacy observed in UC mice under different level of bile acids treated with GQD, aims to clarify the impact of bile acids on UC and its therapeutic effects. It further investigates the expression of bile acid receptors in the liver of UC mice, and preliminarily reveals the mechanism through which GQD affects bile acid synthesis in the treatment of UC. A UC mouse model was established using dextran sulfate sodium(DSS) induction. The efficacy of GQD was evaluated by assessing the general condition, disease activity index(DAI) score, colon length, and histopathological changes in colon tissue via hematoxylin and eosin(HE) staining. ELISA and Western blot were used to evaluate the inflammatory response in colon tissue. The total bile acid(TBA) level and liver damage were quantified using an automatic biochemistry analyzer. The expression levels of bile acid receptors and bile acid synthetases in liver tissue were detected by Western blot and RT-qPCR. The results showed that compared with the model group, GQD treatment significantly improved the DAI score, colon shortening, and histopathological damage in UC mice. The levels of pro-inflammatory factors TNF-α and IL-6 in the colon were significantly reduced. Serum TBA levels were significantly decreased, while alkaline phosphatase(ALP) levels significantly increased. After administration of cholic acid(CA), UC symptoms in the CA + GQD group were significantly aggravated compared with the GQD group. The DAI score, degree of weight loss, colon injury, serum TBA, and liver injury markers all increased significantly. However, compared with the CA group, the CA + GQD group showed a marked reduction in TBA levels and a significant improvement in UC-related symptoms, indicating that GQD can alleviate UC damage exacerbated by CA. Further investigation into the expression of bile acid receptors and synthetases in the liver showed that under GQD treatment, the expression of farnesoid X receptor(FXR) and small heterodimer partner(SHP) significantly increased, while the expression of G protein-coupled receptor 5(TGR5) and cholesterol 7α-hydroxylase(Cyp7A1) significantly decreased. These findings suggest that GQD may affect bile acid receptors and synthetases, inhibiting bile acid synthesis through the FXR/SHP pathway to treat UC.
Animals ; Colitis, Ulcerative/genetics* ; Bile Acids and Salts/biosynthesis* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Male ; Humans ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Colon/metabolism* ; Disease Models, Animal ; Liver/metabolism* ; Mice, Inbred C57BL

Parkinson's disease is a neurodegenerative disease that mostly occurs in middle-aged and elderly people. It is characterized by progressive loss of dopaminergic neurons in the substantia nigra and aggregation of Lewy bodies, resulting in a series of motor symptoms and non-motor symptoms. Depression is the most important manifestation of non-motor symptoms, which seriously affects the quality of life of patients. Clinicians often use antidepressant drugs to improve the depressive symptoms of patients with Parkinson 's disease, but it is still urgent to solve the problems of drug side effects and drug resistance caused by such methods. Repetitive transcranial magnetic stimulation is a safe and non-invasive neuromodulation technique that can change the excitability of the corticospinal tract, induce the release of dopamine and other neurotransmitters, and further improve the depressive symptoms of patients with Parkinson 's disease. Based on this, this paper discusses and summarizes the research progress on the efficacy and potential mechanism of repetitive transcranial magnetic stimulation for improving depression in Parkinson 's disease at home and abroad, in order to provide reference for related clinical application research.
Humans ; Parkinson Disease/psychology* ; Transcranial Magnetic Stimulation/methods* ; Depression/etiology*

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

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 explore the current situation of the clean operating rooms in Guangdong provincial hospitals of traditional Chinese medicine or integrated Chinese and western medicine to provide references for standardizing the construc-tion of the clean operating room.Methods A questionnaire was designed according to GB 50333-2013 Architectural technical code for hospital clean operating department and WS/T 368-2012 Management specification of air cleaning technique in hospitals,and a questionnaire survey and field investigation were conducted from March to October 2021 on the operating rooms of 64 secondary and above hospitals of traditional Chinese medicine or integrated Chinese and western medicine in Guangdong province,which involved in the basic situation of the operating rooms,general requirements for constructing clean operating rooms,requirements for the layout of clean operating rooms and architectural decorations of the clean operating rooms.Results Of the 64 hospitals surveyed there were 51 ones(79.7％)with clean operating rooms.Tertiary hospitals were mainly equipped with Class Ⅲ clean operating rooms(45.8％),secondary hospitals were provided with general operating rooms(35.0％)and Class Ⅲ clean operating rooms(29.2％),and the differences in the types and classes of the operating rooms in levels of hospitals were statistically significant(P＜0.001).The proportions of tertiary hospitals configured with clean operating rooms and the highest configuration of Class I clean operating rooms were also significantly higher than those of secondary hospitals(94.3％vs 62.1％and 88.6％vs 44.8％,respectively),with statistically significant differences(P＜0.05).There were 66.7％hospitals equipped with negative pressure operating rooms;more than 1/2(56.9％)of the hospitals had the service time of their clean operating rooms longer than 10 years.All the tertiary hospitals did not have air shower rooms in their walkways,while 16.7％secondary hospitals did,with the difference being statistically significant(P＜0.05).Most of the building decorations of clean operating rooms in all the hospitals complied with the specifications(compliance rate＞80.0％),and the difference was not statistically significant between the secondary and tertiary hospitals(P＞0.05);the compliance rate of the decrations of the tertiary hospitals was 78.8％for the requirements of general principle,which was obviously lower than that of the secondary hospitals(100％),with the differences being statistically significant(P＜0.05).Conclusion The clean operating rooms in Guangdong provincial hospitals of traditional Chinese medicine or integrated Chinese and western medicine behave well in configuration,while have some defficiencies in general requirements,layout and building,and necessary guidance,supervision and management have to be involved in to standardize the construction of clean operating rooms.[Chinese Medical Equipment Journal,2024,45(10):77-83]

Objective To observe the effects of matrine on the proliferation,migration,and invasion of human neuroblastoma cells,and to investigate its potential mechanism.Methods This study was divided into AS experimental group(SK-N-AS cells treated with IC50 concentration of matrine),AS blank group(SK-N-AS cells cultured under normal conditions),AS control group(SK-N-AS cells treated with an equal amount of dimethyl sulfoxide),DZ experimental group(SK-N-DZ cells treated with IC50 concentration of matrine),DZ blank group(SK-N-DZ cells cultured under normal conditions),and DZ control group(SK-N-DZ cells treated with an equal amount of dimethyl sulfoxide).Scratch assay and Transwell chamber were used to measure the effect of matrine on the migration and invasion.The expression of E-cadherin,N-cadherin and Vimentin were tested by Western blot.Results After different intervention,the migration percentages of AS blank group,AS control group,AS experimental group,DZ blank group,DZ control group and DZ experimental group were(66.32±3.12)％,(65.27±3.44)％,(23.73±0.79)％,(46.25±4.68)％,(44.15±5.60)％and(16.77±3.52)％,respectively;the number of invasive cells were 870.45±19.32,865.32±23.39,492.74±16.81,1 198.10±43.71,1 203.03±71.91 and 891.69±42.62,respectively;the expression levels of E-cadherin protein were(100.00±11.72)％,(105.65±13.11)％,(477.20±29.71)％,(100.00±12.54)％,(97.78±12.77)％and(240.53±12.23)％,respectively;the expression levels of N-cadherin protein were(100.00±15.44)％,(103.90±10.76)％,(43.52±9.96)％,(100.00±10.12)％,(104.95±10.49)％and(38.39±8.70)％,respectively;Vimentin protein expression levels were(100.00±9.51)％,(97.39±11.33)％,(59.13±10.25)％,(100.00±13.20)％,(96.27±11.01)％and(47.67±9.48)％,respectively.There were statistically significant differences in the above indexes between the AS group and the AS blank group(P＜0.01,P＜0.001),and there were statistically significant differences between the above indexes in the DZ group and the DZ blank group(P＜0.01,P＜0.001).Conclusion Matrine inhibits the proliferation,migration,and invasion of neuroblastoma SK-N-AS and SK-N-DZ cells,potentially through suppressing epithelial-mesenchymal transition.