BACKGROUND:Excessive accumulation of uric acid in the body can lead to diseases such as hyperuricemia and gout,which is a risk factor for cardiovascular and renal dysfunction.Many sports medicine organizations at home and abroad advocate the formulation of exercise prescription to prevent and treat chronic diseases,but this method has not been effectively carried out in the prevention and treatment of hyperuricemia. OBJECTIVE:Based on an overview of the formation of hyperuricemia and the regulation of uric acid by exercise and its related mechanisms,to condense a program suitable for popular exercise to prevent and assist in the treatment of hyperuricemia,and to propose precautions to be taken when exercising for patients with different stages of hyperuricemia. METHODS:PubMed and CNKI were searched for relevant literature published before October 2023 using the keywords of"uric acid,gout,aerobic exercise,strength training,high-intensity interval training,obesity"in English and Chinese,respectively.Initial screening was done by reading the titles and abstracts to exclude repetitive studies and literature with irrelevant content,and finally 64 papers were included for review. RESULTS AND CONCLUSION:The formation of hyperuricemia is caused by excessive synthesis of uric acid by the liver,insufficient excretion by the kidneys,or both.Exercise can improve the uric acid level in the body by regulating the activity of antioxidant enzymes,the expression of uric acid excretion protein and lipid metabolism.Aerobic exercise,strength training,high-intensity intermittent exercise can effectively regulate uric acid levels,reduce inflammation,promote the expression of uric acid excretion protein and lipid metabolism,and achieve good results in the prevention and treatment of hyperuricemia.Currently,there is a lack of research on the mechanisms underlying direct regulation of uric acid levels by exercise,and future studies need to explore in greater depth the possible mechanisms of regulation of uric acid levels by exercise and refine the effects of different exercise modalities on patients with different characteristics of hyperuricemia.

Objective To analyze the effect of Hedysari Radix Chinese herbal pieces treatment in acute inferior myocardial infarction patients undergoing percutaneous coronary intervention(PCI).Methods A total of 200 patients with acute inferior myocardial infarction undergoing emergency PCI admitted to department of cardiology of Shijiazhuang People's Hospital from March 31,2020 to March 31,2023 were selected as the study objects.The patients were randomly divided into a control group and a treatment group according to a digital random table method.The control group received routine treatment after PCI,and the patients drank 500 mL of warm water in the morning and afternoon every day,continuing this regimen for up to 30 days post-surgery.The treatment group took 10 g of Hedysari Radix Chinese Herbal pieces in 500 mL of boiling water in the morning and afternoon,soaking it and drinking it coolly and temperately,continuing to take it until 30 days after surgery.Blood pressure,Dopamine dosage,and duration were observed in all patients on 1-5 days after surgery.Major adverse cardiovascular event(MACE),such as cardiac death,myocardial infarction,heart failure,and re-admission were tracked in all patients within 30 days,and adverse reactions and clinical symptom improvement were followed up,using the somatic self-rating scale(SSS).Results The total Dopamine dose in the treatment group was significantly lower than that in the control group(mg:960.4±287.9 vs.1 160.4±610.5,P<0.05),and the duration of use was significantly shorter than that in the control group(hours:60.7±16.9 vs.71.6±20.4,P<0.05).The systolic blood pressure in the treatment group was significantly higher than that in the control group at 1 day after PCI[mmHg(1 mmHg≈0.133 kPa):96.8±19.5 vs.90.2±11.1,P<0.05],until 5 days after PCI(mmHg:106.3±14.4 vs.99.7±13.9,P<0.05),while the changes in diastolic blood pressure were not significant in both groups.The incidence of MACE in the treatment group was significantly lower than that in the control group within 30 days after PCI[4.0%(4/100)vs.13.0%(13/100),P<0.05],and the SSS score was also significantly lower than that in the control group(31.56±11.58 vs.40.72±18.67,P<0.05).Conclusion The effect of Hedysari Radix Chinese herbal pieces treatment can significantly improve clinical efficacy without significant adverse reactions.

The killing effect of radiation therapy on healthy cells has led to the creation of targeted radionuclide therapy,which effectively reduces the damage to surrounding normal cells.At present,alpha(α)and beta(β)radionuclides are the research hotspots of targeted therapy.Numerous preclinical and clinical studies have shown that radiation therapy not only has local anti-tumor effects,but also exerts systemic anti-tumor effects by triggering the body's immune response.This paper describes in detail the characteristics and clinical applications of commonly used radionuclides,and discusses the mechanism of radiation-triggered body immune response as well as the related research on the combined use of radiation therapy,targeted radionuclide therapy and immunotherapy.

Targeted radiation therapy using radionuclides is a favored approach for treating tumors.This procedure involves the delivery of drugs to the lesion site via carriers or interventional methods,followed by the emission of radiation energy that selectively irradiates the lesion tissue.This approach minimizes damage to normal tissue and achieves the desired therapeutic effect.Factors such as the type of therapeutic radionuclide,radiation energy,physical half-life,method of preparation,and toxicity determine their clinical application.In this paper,the characteristics and clinical application of therapeutic radionuclides were reviewed to providing reference for the clinical application of targeted therapeutic radionuclides.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

OBJECTIVE To explore the mechanism of action of Fushao Diqin Decoction in the treatment of colorectal cancer.METHODS In vitro cell experiments were conducted using Fushao Diqin Decoction to treat colorectal cancer CT-26 cells,and the cell proliferation and migration abilities were detected.Flow cytometry was used to detect the levels of reactive oxygen species(ROS)in colorectal cancer CT-26 cells,as well as the levels of iron ions(Fe2+),malondialdehyde(MDA),and the activity of su-peroxide dismutase(SOD).PCR Array and Western blot methods were used to analyze and verify the differential gene expression of ferroptosis.Balb/c mice were randomly divided into a blank control group,a model group,an oxaliplatin group(1.5 mg·kg-1·d-1),a low-dose group of Fushao Diqin Decoction(4.49 g·kg-1·d-1),a medium dose group of Fushao Diqin Decoction(8.97 g·kg-1·d-1),and a high-dose group of Fushao Diqin Decoction(17.94 g·kg-1·d-1)for in vivo animal experi-ments.The effects of Fushao Diqin Decoction on Fe2+,ROS,MDA levels,SOD activity,and Nrf2,Keap1,SLC7A11 and GPX4 ex-pression levels in mouse tumor tissues were tested.RESULTS In vitro cell experiments showed that compared with the blank control group,Fushao Diqin Decoction significantly inhibited the proliferation and migration of colorectal cancer CT-26 cells in a dose-de-pendent manner.Fushao Diqin Decoction could increase the Fe2+content(P＜0.05)and ROS level(P＜0.01)in colorectal cancer CT-26 cells,increase the MDA level in CT-26 cells of colorectal cancer(P＜0.01)and significantly reduce SOD activity(P＜0.01).Iron death PCR array analysis found that compared with the blank control group,after intervention with Fushao Diqin Decoc-tion,the expression of genes GPX4 and SLC7A11 was significantly downregulated,while the expression of GSTA1,HMOX1,Ca9,Chac1,Keap1,Sqstm1,NOX1,FTH1,Tfr1,SAT2,Pparg,and Hamp was significantly upregulated.Western blot analysis revealed that after intervention with Fushao Diqin Decoction,the expression of Keap1 protein was upregulated(P＜0.01),while the expression of Nrf2,SLC7A11,and GPX4 proteins was downregulated(P＜0.01)in colorectal cancer CT-26 cells.The results of in vivo animal experiments showed that Fushao Diqin Decoction significantly inhibited the growth of subcutaneous transplanted tumors in mice(P＜0.05),increased the degree of tumor tissue necrosis,and levels of Fe2+,ROS,and MDA(P＜0.05,P＜0.01),decreased SOD ac-tivity(P＜0.01)and upregulated Keap1 protein expression(P＜0.01),while downregulated Nrf2,SLC7A11,and GPX4 protein ex-pression(P＜0.01).CONCLUSION Fushao Diqin Decoction has an anti-colorectal cancer effect and may promote ferroptosis in colorectal cancer cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway to exert its anti-colorectal cancer effect.

Objective:To investigate corneal transparency alteration in patients with type 2 diabetes and its influencing factors.Methods:A case-control study was conducted.A total of 52 patients with type 2 diabetes mellitus (DM) (104 eyes) and 23 age-matched healthy controls (46 eyes) were enrolled as DM group and normal control group in the Second Affiliated Hospital of Anhui Medical University from October 1, 2020 to October 30, 2021.Patients with DM were further divided into non-diabetic retinopathy (non-DR) and DR groups according to their fundus conditions.Corneal densitometry (CD) was evaluated using the Pentacam.According to its built-in program, the cornea was divided into anterior, intermediate, and posterior layers and subdivided into 0-2 mm, >2-6 mm, >6-10 mm, and >10-12 mm annular regions with the corneal apex as the center of the circle.Pentacam automatically calculated the CD value of each corneal layer and region as well as the total CD value.The influencing factors of total CD value in diabetes group were analyzed by a multivariate linear regression analysis model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Anhui Medical University (No.YX2023-129[F1]).Written informed consent was obtained from each subject before any medical examination.Results:The total CD value of diabetes group was 20.24±3.10, which was significantly higher than 18.79±3.31 of normal control group ( t=-2.583, P=0.011).The CD values of the anterior layer, intermediate layer, 0-2 mm, and >2-6 mm regions were significantly higher in diabetes group than in normal control group (all at P<0.05).The CD values in the anterior layer were higher in non-DR and DR groups than in normal control group, and the CD values and total CD values in the middle and posterior layers were higher in non-DR group than in normal control group and DR group, and the differences were statistically significant (all at P<0.05).The CD values in the 0-2 mm and >2-6 mm regions were significantly higher in non-DR group than in normal control group, and the CD value in the >6-10 mm annular region was significantly higher in non-DR group than in DR group and normal control group (all at P<0.05).Multivariate linear regression analysis showed that age and glycosylated hemoglobin (HbA1c) level were the main influencing factors for the increase in CD values in diabetic patients ( β=0.266, P<0.001; β=0.423, P=0.003). Conclusions:The decrease of corneal transparency precedes the appearance of DR in patients with diabetes.Poor control of HbA1c level in diabetic patients may cause the decline of corneal transparency.

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

OBJECTIVE: To explore the clinical phenotype and genetic basis of a neonate with Au-Kline syndrome (AKS). METHODS: Clinical data and result of genetic testing of a neonate with AKS who was admitted to the Affiliated Provincial Children's Hospital of Anhui Medical University in January 2021 were retrospectively analyzed. Relevant literature was searched from the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed databases using key words "Au Kline syndrome", "Au-Kline syndrome", "HNRNPK" and "AKS". The research period was set as from January 1, 2000 to December 31, 2020. RESULTS: The male newborn has manifested feeding difficulties, hypotonia, absence of the upper jaw to the uvula and facial dysmorphism. Trio-whole exome sequencing revealed that he has harbored a frameshift c.478dupA (p.Ile160AsnfsTer7) variant of the HNRNPK gene, which was varified by Sanger sequencing to have a de novo origin. The variant has not been included in the databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). Literature retrieval has identified 14 children with AKS and de novo mutations of the HNRNPK gene. Their clinical manifestations have included growth and motor retardation, various degree of mental retardation, facial dysmorphism and a high frequency of congenital heart malformations. CONCLUSION The AKS in this child may be attributed to the c478dupA frameshifting variant of the HNRNPK gene. Diagnosis of AKS should be suspected for children with mental retardation and multiple congenital malformation syndromes including Kabuki syndrome.
Humans ; Male ; Abnormalities, Multiple/genetics* ; Genetic Testing ; Heterogeneous-Nuclear Ribonucleoprotein K/genetics* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Infant, Newborn

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease. Early brain injury (EBI) and cerebral vasospasm are the main reasons for poor prognosis of SAH patients. The specific inhibitor of histone deacetylase 6 (HDAC6), tubastatin A (TubA), has been proved to have a definite neuroprotective effect on a variety of animal models of acute and chronic central nervous system diseases. However, the neuroprotective effect of TubA on SAH remains unclear. This study aims to investigate the expression and localization of HDAC6 in the early stage of SAH, and to evaluate the protective effects of TubA on EBI and cerebral vasospasm after SAH and the underlying mechanisms. METHODS: Adult male SD rats were treated with modified internal carotid artery puncture to establish SAH model. In the first part of the experiment, rats were randomly divided into 6 groups: a sham group, a SAH-3 h group, a SAH-6 h group, a SAH-12 h group, a SAH-24 h group, and a SAH-48 h group. At 3, 6, 12, and 24 h after SAH modeling, the injured cerebral cortex of rats in each group was taken for Western blotting to detect the expression of HDAC6. In addition, the distribution of HDAC6 in the cerebral cortex of the injured side was measured by immunofluorescence double staining in SAH-24 h group rats. In the second part, rats were randomly divided into 4 groups: a sham group, a SAH group, a SAH+TubA_L group (giving 25 mg/kg TubA), and a SAH+TubA_H group (giving 40 mg/kg TubA). At 24 h after modeling, the injured cerebral cortex tissue was taken for Western blotting to detect the expression levels of HDAC6, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining to detect apoptosis, and hematoxylin and eosin (HE) staining to detect the diameter of middle cerebral artery. RESULTS: The protein expression of HDAC6 began to increase at 6 h after SAH (P<0.05), peaked at 24 h (P<0.001), and decreased at 48 h, but there was still a difference compared with the sham group (P<0.05). HDAC6 is mainly expressed in the cytoplasm of the neurons. Compared with the sham group, the neurological score was decreased significantly and brain water content was increased significantly in the SAH group (both P<0.01). Compared with the SAH group, the neurological score was increased significantly and brain water content was decreased significantly in the SAH+TubA_H group (both P<0.05), while the improvement of the above indexes was not significant in the SAH+TubA_L group (both P>0.05). Compared with the sham group, the expression of eNOS was significantly decreased (P<0.01) and the expressions of iNOS and HDAC6 were significantly increased (P<0.05 and P<0.01, respectively) in the SAH group. Compared with the SAH group, the expression of eNOS was significantly increased, and iNOS and HDAC6 were significantly decreased in the SAH+TubA group (all P<0.05). Compared with the SAH group, the number of TUNEL positive cells was significantly decreased and the diameter of middle cerebral artery was significantly increased in the SAH+TubA group (both P<0.05) . CONCLUSIONS HDAC6 is mainly expressed in neurons and is up-regulated in the cerebral cortex at the early stage of SAH. TubA has protective effects on EBI and cerebral vasospasm in SAH rats by reducing brain edema and cell apoptosis in the early stage of SAH. In addition, its effect of reducing cerebral vasospasm may be related to regulating the expression of eNOS and iNOS.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Vasospasm, Intracranial/metabolism* ; Histone Deacetylase Inhibitors/therapeutic use* ; Neuroprotective Agents/therapeutic use* ; Histone Deacetylase 6/pharmacology* ; Apoptosis ; Brain Injuries/drug therapy*