Objective To explore the risk factors for acute thrombosis of arteriovenous fistulae(AF)in maintenance hemodialysis(MHD)patients and the construction of a Nomogram prediction model.Methods A total of 418 patients who underwent MHD treatment in the outpatient clinic of the Third Affiliated Hospital of Xinxiang Medical University from December 2020 to December 2022 were selected for the study.The patients were divided into the acute thrombosis group(n=32)and non-acute thrombosis group(n=386)according to whether acute thrombosis of AF was formed or not.The influencing factors affecting acute thrombosis of AF in MHD patients were analyzed using univariate and multivariate analysis.A Nomogram predic-tion model was established based on their independent risk factors,and Bootstrap was used to validate the efficacy of the Nomo-gram model.Results The complicated diabetes,complicated hypotension,puncture failure on dialysis,calcium-phosphorus product,hypersensitive C-reactive protein(hs-CRP),total cholesterol(TC),and low density lipoprotein-cholesterol(LDL-C)levels in patients in the acute thrombosis group were significantly higher than those in the non-acute thrombosis group(P＜0.05);logistic regression analysis showed that diabetes,hypotension,puncture failure on dialysis,calcium-phosphorus product elevation,high hs-CRP and high LDL-C level were the independent risk factors affecting acute thrombosis of AF in patients undergoing MHD(P＜0.05);the Nomogram model was constructed based on the 6 independent risk factors,and the consistency index(C-index)of the model was 0.893(95％confidence interval:0.833-0.928);in addition,its calibration curve and the standard curve were well fitted,the area under the curve was 0.918.Conclusion Diabetes,hypotension,puncture failure during dialysis,calcium-phosphorus product elevation,and high levels of hs-CRP and LDL-C are the risk factors for acute thrombosis of AF in patients undergoing MHD,and the Nomogram model constructed based on the independent risk factors has excellent predictive ability in predicting the occurrence of acute thrombosis of AF in patients undergoing MHD,which can help in the early screening of patients with high risk of clinical acute thrombosis.

Objective To investigate the effect of hyperbaric oxygen(HO)combined with ginkgo biloba extract(GBE)in elderly patients with vascular dementia.Methods A total of 132 elderly patients with vascular dementia who visited the Ninth People's Hospital of Zhengzhou from January 2019 to December 2022 were selected as the research subjects,and they were divided into the observation group and control group using a random number table method,with 66 patients in each group.Both groups of patients received routine treatment,while the control group received HO therapy once a day;patients in the observation group were treated with HO combined with GBE once a day;both groups of patients were treated continuously for one month.The cognitive function and activities of daily living of two groups of patients before and after treatment were evaluated using the Montreal Cognitive Assessment(MoCA)scale and Barthel index,and the clinical efficacy of the two groups of patients after treatment was evaluated based on the MoCA score and Barthel Index.Transcranial Doppler ultrasound was used to detect the average blood flow velocity(ABFV)of the anterior cerebral artery(ACA),posterior cerebral artery(PCA),middle cerebral artery(MCA)and vertebral artery(VA)in the two groups of patients before and after treatment.Results There was no statistically significant difference in MoCA score and Barthel index between the two groups of patients before treatment(P＞0.05).After treatment,the MoCA score and Barthel index of both groups of patients were higher than those before treatment(P＜0.05),and the MoCA score and Barthel index in the observation group were higher than those in the control group(P＜0.05).After treatment,the total effective rates of the control group and the observation group were 84.85％(56/66)and 95.45％(63/66),respectively,and the total effective rate of the observation group was significantly higher than that of the control group(x2=4.181,P＜0.05).There was no statistically significant difference in the ABFV of the ACA,PCA,MCA and VA between the two groups of patients before treatment(P＞0.05).After treatment,the ABFV of the ACA,PCA,MCA and VA in the two groups of patients was higher than that before treatment(P＜0.05),and the observation group was higher than the control group(P＜0.05)in terms of the ABFV of the ACA,PCA,MCA and VA.The total incidence of adverse reactions in the control group and observation group during treatment was 16.67％(11/66)and 18.18％(12/66),respectively,and there was no statistically significant difference in the total incidence of adverse reactions between the two groups of patients(x2=0.218,P＞0.05).Conclusion The combination of HO and GBE can significantly improve cerebral blood flow status and cognitive dysfunction in patients with vascular dementia and enhance their activities of daily living with good overall efficacy and high safety.

5-hydroxytryptamine(5-HT)is a monoamine neurotransmitter,which plays a key role in regulating gastroin-testinal motility,antioxidation and immunomodulation.Inflammatory bowel disease(IBD)is characterized by repetitive epi-sodes of inflammation of the gastrointestinal tract,and its pathogenesis hasn't been illustrated completely.In recent years,the role of 5-HT in the development of IBD has drawn attention gradually.Therefore,this article reviews the advances of 5-HT in the pathogenesis of IBD and focuses on the pathways of autophagy,oxidative stress,inflammatory reaction,endoplasmic reticu-lum stress and gut microbiota through which 5-HT causes IBD,with the hope of providing insights for identifying novel prognos-tic biomarkers and exploring new therapies.

Radix et Rhizoma Rhei is one of the major Chinese medicinal herbs,with a long medicinal history and extensive clinical application.It has the effects of purgation,clearing heat and fire,cooling blood and detoxifying,expelling stasis and channeling meridian,diuresis and retreating yellow,etc.Its chemical constituents mainly include anthraquinones,anthrones,stilbenes,benzophenones,polysaccharides,tannins,and volatile oils.The pharmacological effects mainly include purgation,anti-inflammation,anti-tumor,lipid regulation,renal protection,liver protection,and anti-angiogenesis.This article summarizes the main chemical constituents and modern pharmacological effects of Radix et Rhizoma Rhei,aiming to provide a reference for the research of clinical use and pharmacological effects of Radix et Rhizoma Rhei.

Programmed cell death protein ligand-1(PD-L1)is an important immune checkpoint molecule that plays an important role in regulating the body's immune response.Several clinical studies have shown that the expression level of PD-L1 in tumors is closely related to the efficacy of immune checkpoint inhibitors.Due to the spatial and temporal heterogeneity of tumors,immunohistochemical methods commonly used in clinical practice cannot accurately and comprehensively reflect the ex-pression level of PD-L1 in patients.Given that nuclear-medicine molecular imaging technology can noninvasively,real-time,dy-namically and visually monitor the expression level of PD-L1 in vivo at the molecular level,this article mainly focuses on the re-search of peptide-based radiolabeled molecular probes targeting PD-L1,with the aim of providing guidance for the search of no-vel peptide molecular probes for immunoimaging as well as for the screening of immunotherapy-suitable patients and evaluation of therapeutic efficacy,and other clinical applications.

Ubiquitin-specific proteases(USPs)are one of the many subfamilies of the deubiquitinating enzyme family,with a variety of functional structural domains and biological functions,which can regulate ubiquitination through the dissocia-tion of ubiquitin from protein substrates,thereby regulating apoptosis,proliferation,metastasis,as well as gene transcription,mesenchymal transition,and immune responses.Ubiquitin is a small protein that marks proteins for degradation and is present in most eukaryotic cells,which hydrolyses proteins through a complex chain reaction of ubiquitination.There are different sites of ubiquitination complex chain reactions,and USPs can act on them and affect ubiquitination in organisms,playing different roles in protein degradation.USPs are expressed in a variety of tumors and participate in tumorigenesis and development through a series of mechanisms,which can be used as cancer therapeutic targets.This article reviews the progress of research on the role of USPs in gastric cancer,in order to provide information for the development of new drugs targeting USPs for the treatment of gastric cancer.

Objective To investigate the changes in microglia phenotype after cerebral ischemia reperfusion(1R)injury and the effects of adenosine on nerve injury of cerebral IR injured rats.Methods Thirty-six healthy male Sprague Dawley rats were randomly divided into the sham operation(Sham)group,IR group,and adenosine pretreatment(AP)group,with 12 rats in each group.Before modeling,rats in the AP group were intraperitoneally injected with 2 mL of adenosine injection daily for 3 consecutive days,and rats in the Sham group and IR group were intraperitoneally injected with 2 mL of normal saline daily for 3 consecutive days.The middle cerebral artery occlusion models of rats in the IR group and AP group were constructed by using the suture-occluded method,and only the carotid artery of rats was isolated in the Sham group without ligation of blood vessels.At 2 hours after modeling,the neuroethology of rats in each group were evaluated according to a 5-point neurobehavioral scale.At 24 hours after restoring the blood perfusion in the middle cerebral artery,the rats in each group were executed,and their brain tissues were removed.The morphological changes of the brain tissues in the ischemic penumbra region were observed after hematoxylin-eosin(HE)staining.The co-expression of M1-type microglia markers and M2-type microglia markers was detected by immunofluorescence staining.The relative expression levels of pro-inflammatory factors inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α)and interleukin(IL)-1β released by M1-type microglia,and anti-inflammatory factors IL-4,IL-10 and transforming growth factor-β(TGF-β)released by M2-type microglia were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Results The neurobehavioral scores of rats in the IR group and AP group were significantly higher than those in the Sham group,and the neurobehavioral score of rats in the IR group was significantly higher than that in the AP group(P＜0.05).HE staining results showed that the brain cells of rats in the Sham group were structurally complete and tightly arranged,with visible nuclei and no interstitial edema;the brain cells of rats in the IR group were structurally damaged and irregularly arranged,with loose cytoplasm and vacuoles in the cytosome;the structure of brain cells of rat in the AP group was better than that in the IR group,and there were many regularly-arranged normal cells,with complete nuclei.Immunofluorescence staining results showed that the number of M1-type and M2-type microglia in the ischemic penumbra region of rats in the IR group and AP group was significantly higher than that in the Sham group;the number of M1-type microglia in the IR group was significantly higher than that in the AP group,and the number of M2-type microglia was significantly lower than that in the AP group(P＜0.05).qRT-PCR results showed that the relative expression levels of pro-inflammatory cytokines TNF-α,IL-1β,iNOS and anti-inflammatory cytokines IL-4,IL-10,TGF-β in the IR group and AP group were significantly higher than those in the Sham group(P＜0.05);the relative expression levels of pro-inflammatory factors TNF-α,IL-1β and iNOS in the AP group were significantly lower than those in the IR group(P＜0.05),while the relative expression levels of anti-inflammatory factors IL-4,IL-10 and TGF-β were significantly higher than those in the IR group(P＜0.05).Conclusion AP can promote the polarization of microglia from M1 type to M2 type,inhibit the release of pro-inflammatory factors,increases the expression of anti-inflammatory factors,and thus has a neuroprotective effect on rats after cerebral IR injury.

Objective To explore the protective effect and related mechanism of microRNA(miR)-375-5p on heart failure(HF)rats.Methods Fifty male Sprague Dawley rats were randomly divided into the sham operation group,HF group,miR-NC group,miR-375-5p group and miR-375-5p+Compound C(CC)group,with 10 rats in each group.The rats in the HF group,miR-NC group,miR-375-5p group and miR-375-5p+CC group were intraperitoneally injected with adriamycin solution to prepare HF models,and the rats in the sham operation group were intraperitoneally injected with an equal amount of NaCl solution.On the next day after modeling,the rats in the miR-375-5p group were intravenously injected with 100 μL of miR-375-5p mimics via tail vein;the rats in the miR-NC group were intravenously injected with 100 μL of miR-NC mimics via tail vein;the rats in the sham operation group and HF group were intravenously injected with an equal volume of normal saline via tail vein;the rats in the miR-375-5p+CC group were intravenously injected with 100 μL of miR-375-5p mimics and adenosine monophosphate-activated protein kinase(AMPK)inhibitor CC(0.2 mg·kg-1)via tail vein;and the rats in each group were administered once daily for 4 consecutive weeks.The cardiac function parameters of rats in each group were detected by color Doppler ultrasound;the expression levels of miR-375-5p in myocardial tissues of rats in each group were detected by reverse transcription polymerase chain reaction;the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,malondial-dehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in serum of rats in each group were measured by enzyme-linked immunosorbent assay;the pathological changes in myocardial tissues of rats in each group were observed by hematoxylin-eosin staining;the myocardial cell apoptosis of rats in each group was detected by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling assay;and the relative expression levels of phosphorylated-AMPK(p-AMPK),AMPK and sirtuin 3(SIRT3)proteins in myocardial tissues of rats in each group were measured by Western blot.Results Compared with the sham operation group,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),serum SOD activity,GSH level,p-AMPK/AMPK,miR-375-5 p expression level,and relative expression level of SIRT3 protein in myocardial tissues of rats in the HF group,miR-NC group and miR-375-5p group significantly decreased,while the left ventricular end-diastolic dimension(LVEDD),left ventricular end-systolic dimension(LVESD),myocardial cell apoptosis rate,and serum levels of TNF-α,IL-6,IL-1β and MDA significantly increased(P＜0.05).There was no significant differences in LVEF,LVFS,LVEDD,LVESD,myocardial cell apoptosis rate,serum levels of TNF-α,IL-6,IL-1β,MDA and GSH,SOD activity,p-AMPK/AMPK,miR-375-5p expression level,and relative expression level of SIRT3 protein in myocardial tissues of rats between the miR-NC group and the HF group(P＞0.05).Compared with the HF group,LVEF,LVFS,serum SOD activity,GSH level,p-AMPK/AMPK,miR-375-5p expression level,and relative expression level of SIRT3 protein in myocardial tissues of rats in the miR-375-5p group significantly increased,while the LVEDD,LVESD,myocardial cell apoptosis rate,and serum levels of TNF-α,IL-6,IL-1β and MDA significantly decreased(P＜0.05).Compared with the miR-375-5p group,LVEF,LVFS,serum SOD activity,GSH level,p-AMPK/AMPK,miR-375-5p expression levels,and relative expression level of SIRT3 protein in myocardial tissues of rats in the miR-375-5p+CC group significantly decreased,while the LVEDD,LVESD,myocardial cell apoptosis rate,and serum levels of TNF-α,IL-6,IL-1β and MDA significantly increased(P＜0.05).Myocardial cells of rats in the sham operation group were regularly arranged,with obvious nuclei and no inflammatory cell infiltration;myocardial cells of rats in the HF group were altered morphologically and arranged irregularly,with enlarged cell gaps,lighter staining,myocardial fibrosis,and a large number of inflammatory cell infiltration.There was no significant difference in the pathological changes of myocardial tissues between the HF group and the miR-NC group.Compared with the HF group,myocardial cells of rats in the miR-375-5p group were arranged orderly,and the degree and extent of necrocytosis were reduced.The pathological changes in myocardial cells of rats were similar between the miR-375-5p+CC group and the HF group.Conclusion miR-375-5p can inhibit the apoptosis of myocardial cells in rats with HF,which may be related to its activation of the AMPK/SIRT3 signaling pathway.

Objective To investigate the effect and mechanism of shikonin on the proliferation,migration,invasion and apoptosis of human gastric cancer MGC803 cells.Methods The MGC803 cells in the logarithmic growth phase were randomly divided into the blank control group,shikonin group,shikonin+insulin-like growth factor-1(IGF-1)group,and shikonin+LY294002 group.Cells in the blank control group were cultured in drug-free medium,cells in the shikonin group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1,cells in the shikonin+IGF-1 group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1 and IGF-1 with a final concentration of 10 μmol·L-1,and cells in the shikonin+LY294002 group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1 and LY294002 with a final concentration of 30 μmol·L-1.After 24 h of culture,the cell proliferation was detected by cell counting kit-8,the cell apoptosis was detected by flow cytometry,the cell migration was detected by scratch assay,and the cell invasion was detected by Transwell assay.The expression levels of B cell lymphoma-2(Bcl-2),Bcl-2 related X protein(Bax),cytochrome C(Cyt C),cleaved caspase-3,cleaved caspase-9,phosphoinositide 3 kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(PKB),and phosphorylated PKB(p-PKB)proteins were measured by using Western blot.Results The MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin group were significantly higher than those in the blank control group(P＜0.05);the MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin+IGF-1 group were significantly lower than those in the shikonin group(P＜0.05);and the MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin+LY294002 group were significantly higher than those in the shikonin group(P＜0.05).The MGC803 cell scratch healing rate and the number of invasive cells in the shikonin group were significantly lower than those in the blank control group(P＜0.05);the MGC803 cell scratch healing rate and the number of invasive cells in the shikonin+IGF-1 group were significantly higher than those in the shikonin group(P＜0.05);and the MGC803 cell scratch healing rate and the number of invasive cells in the shikonin+LY294002 group were significantly lower than those in the shikonin group(P＜0.05).The relative expression level of Bcl-2 protein in MGC803 cells in the shikonin group was significantly lower than that in the blank control group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly higher than those in the blank control group(P＜0.05);the relative expression level of Bcl-2 protein in MGC803 cells in the shikonin+IGF-1 group was significantly higher than that in the shikonin group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly lower than those in the shikonin group(P＜0.05);and the relative expression level of Bcl-2 protein in MGC803 cells in the shikonin+LY294002 group was significantly lower than that in the shikonin group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly higher than those in the shikonin group(P＜0.05).The relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin group were significantly lower than those in the blank control group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin group and the blank control group(P＞0.05);the relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin+IGF-1 group were significantly higher than those in the shikonin group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin+IGF-1 group and the shikonin group(P＞0.05);and the relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin+LY294002 group were significantly lower than those in the shikonin group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin+LY294002 group and the shikonin group(P＞0.05).Conclusion Shikonin can inhibit the proliferation,migration and invasion and promote the apoptosis of human gastric cancer MGC803 cells,which may be related to its inhibition of the PI3K/PKB signaling pathway.

Objective To explore the effect of semaglutide on myocardial injury markers and cardiovascular and cerebrovascular events in patients with type 2 diabetes mellitus(T2DM).Methods A total of 100 patients with T2DM admitted to Xingtai Third Hospital from January to December 2021 were selected as the research subjects,and they were divided into the control group and the observation group by using the random number table,with 50 patients in each group.The patients in both groups were given lifestyle interventions,including reasonable diet,moderate exercise,smoking cessation and alcohol restriction.On this basis,the patients in the control group were given the conventional hypoglycemic drug metformin,and the patients in the observation group were given metformin and semaglutide injection.The patients in both groups were treated for 12 months.Before and after treatment,fasting venous blood was collected from the patients in the two groups,and the levels of glycated hemoglobin(HbA1c)were measured by high-performance liquid chromatography,the fasting plasma glucose(FPG),2-hour postprandial glucose(2hPG),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured by using the glucose oxidase method,and the levels of serum cardiac troponin Ⅰ(cTnⅠ),myoglobin(Myo),and lactate dehydrogenase(LDH)were measured by using the electro-chemiluminescence or enzyme-linked immunosorbent assay.The systolic blood pressure(SBP)and diastolic blood pressure(DBP)in the right upper arm of patients were measured by using an electronic blood pressure monitor.The cardiovascular and cerebrovascular events such as myocardial infarction,unstable angina,heart failure,cardiogenic shock,arrhythmia,ischemic stroke,and hemorrhagic stroke during treatment of patients in two groups were recorded.Results Before treatment,there was no statistically significant difference in the levels of FPG,2hPG,and HbA1c of patients between the two groups(P＞0.05).After treatment,the levels of FPG,2hPG,and HbA1c of patients in the two groups were significantly lower than those before treatment(P＜0.05);and the levels of FPG,2hPG,and HbA1c of patients in the observation group were significantly lower than those in the control group(P＜0.05).Before treatment,there was no statistically significant difference in SBP and DBP of patients between the two groups(P＞0.05).There was no statistically significant difference in SBP and DBP of patients before and after treatment in the control group(P＞0.05);after treatment,the SBP and DBP of patients in the observation group were significantly lower than those before treatment and in the control group(P＜0.05).Before treatment,there was no statistically significant difference in the levels of TC,TG,LDL-C,and HDL-C of patients between the two groups(P＞0.05).There was no statistically significant difference in the levels of TC,TG,LDL-C,and HDL-C of patients before and after treatment in the control group(P＞0.05);after treatment,the levels of TC,TG,and LDL-C of patients in the observation group were significantly lower than those before treatment,while the level of HDL-C was significantly higher than that before treatment(P＜0.05);after treatment,the levels of TC,TG,and LDL-C of patients in the observation group were significantly lower than those in the control group,while the level of HDL-C was significantly higher than that in the control group(P＜0.05).During the treatment period,the incidence of cardiovascular and cerebrovascular events of patients in the control and observation groups was 18.0％(9/50)and 4.0％(2/50),respectively;the incidence of cardiovascular and cerebrovascular events of patients in the observation group was significantly lower than that in the control group(x2=4.320,P＜0.05).Before treatment,there was no statistically significant difference in levels of cTnⅠ,Myo,and LDH of patients between the two groups(P＞0.05).There was no statistically significant difference in the levels of cTnⅠ,Myo,and LDH of patients before and after treatment in the control group(P＞0.05);after treatment,the levels of cTnⅠ,Myo,and LDH of patients in the observation group were significantly lower than those before treatment and in the control group(P＜0.05).Conclusion Semaglutide can obviously reduce blood glucose and pressure,improve blood lipids,reduce the incidence of cardiovascular and cerebrovascular events,and alleviate the degree of myocardial injury in patients with T2DM.