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1.
Article in Chinese | WPRIM | ID: wpr-1017187

ABSTRACT

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation, namely the Warburg effect. Even under aerobic conditions, tumor cells mainly rely on glycolysis to provide energy. Therefore, glucose transporter protein 1(GLUT1), which is involved in the process of glucose metabolism, plays an important role in tumorigenesis, development and drug resistance, and is considered to be one of the important targets in the treatment of malignant tumors. In recent years, research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism, among which the role of GLUT1 is the most critical. In this paper, the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine(TCM) active ingredient nano-delivery system in tumor therapy, aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention(EPR) effect. In summary, the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

2.
Article in Chinese | WPRIM | ID: wpr-1018708

ABSTRACT

Objective To explore the prognostic factor and its predictive value of patients with Wilson disease-related acute-on-chronic liver failure(WD-ACLF).Methods The clinical data of 70 patients diagnosed as WD-ACLF admitted to the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 1,2017 to January 1,2022 were retrospectively collected.According to the 12-week prognosis,patients were divided into survival group(n=36)and death group(n=34).The data of the two groups were analyzed by univariate and multivariate logistic analysis to screen the prognostic risk factors and evaluate their predictive value.The model coefficient is omnibus tested,and the model-fitting degree is evaluated by the Hosmer-Lemeshow test.ROC curve was used to analyze the prognostic value for WD-ACLF between the new model and chronic liver failure-sequential organ failure assessment(CLIF-SOFA)score,model for end-stage liver disease(MELD)score and Child-Turcotte-Pugh(CTP)score.Results A total of 70 WD-ACLF patients were enrolled in present study,including 36 cases in survival group[22 males and 14 females with median age of 30.0(17.3,40.0)]and 34 cases in death group[25 males and 9 females with median age of 34.0(28.8,41.0)].Univariate analysis showed that the course of disease,prothrombin time(PT),activated partial thromboplastin time(APTT)were shorter in survival group than that in death group,the white blood cells(WBC),international normalized ratio(INR),aspartate transaminase(AST),total bilirubin(TBIL),blood urea nitrogen(BUN),creatinine(Cre)and ceruloplasmin(CER)levels and the proportion of infection,ascites,and upper gastrointestinal bleeding were lower in survival group than those in death group,however,the proportion of infection,ascites and upper digestive bleeding in the survival group were lower than those in the death group.Meanwhile,the red blood cells(RBC),hemoglobin(Hb),Na+ and total cholesterol(TC)level in the survival group were higher than those in the death group(P<0.05 or P<0.01).The results of multivariate logistic regression analysis showed that disease course(OR=1.176,95%CI 1.043-1.325),INR(OR=7.635,95%CI 1.767-32.980),TBIL(OR=1.012,95%CI 1.003-1.021),and upper gastrointestinal bleeding(OR=11.654,95%CI 1.029-131.980)were independent risk factors affecting the prognosis of WD-ACLF(P<0.05).Based on the results of logistic regression analysis,a joint model for predicting the prognosis of WD-ACLF was established.The AUC of the model for evaluating the prognosis of WD-ACLF was 0.941,which was greater than the CLIF-SOFA score(AUC=0.802),MELD score(AUC=0.897),and CTP score(AUC=0.722).Conclusions The course of disease,TBIL,INR,and upper gastrointestinal bleeding are risk factors that affect the prognosis of WD-ACLF.The prognosis model established based on this can more accurately predict the prognosis of WD-ACLF patients,and its predictive value is superior to CLIF-SOFA score,MELD score,and CTP score.

3.
Article in Chinese | WPRIM | ID: wpr-1019593

ABSTRACT

This article introduced the basic theory of quantile regression and its application in medical and public health research for methodological reference.We fit the quantile regression model to cross-sectional data from the National Health and Nutrition Examination Survey to estimate the association between sleep duration and depression levels at different quantiles of depression levels.The method showed that among people with low levels of depression,sleep duration was not significantly associated with depression level.While among people with higher levels of depression,the association of sleep duration with depression level became much more pronounced.The real data analysis shows that quantile regression can provide a comprehensive analysis of association between exposure and continuous outcome,and identify subgroups that are more sensitive to exposure,providing recommendations for targeted interventions.The method showed promising application value in medical and public health research.

4.
Journal of Practical Radiology ; (12): 646-649,669, 2024.
Article in Chinese | WPRIM | ID: wpr-1020275

ABSTRACT

Objective To evaluate the application efficacy of low-dose test method combined with variable helical pitch(VHP)technology in computed tomography angiography(CTA)of lower extremity arteries.Methods Eighty patients with CTA imaging of bilateral lower extremity arteries were selected and divided into group A and group B on average.VHP technology was used in group A,and conventional fixed pitch scanning was used in group B.The objective and subjective image quality of the two groups were compared,and the radiation dose and contrast agent dosage of the two groups were recorded and compared.Results The subjective image quality evaluation of group A was significantly better than that of group B,and the difference was statistically significant(Kappa test,P<0.05).In the objective image quality evaluation,the CT value and signal-to-noise ratio(SNR)value of the common iliac artery,popliteal artery and anterior tibial artery in group A were higher than those in group B at the same level,and the differences were statistically significant(P<0.05);The effective dose(ED)value in group A was(6.74±1.20)mSv,and that in group B was(7.93±1.78)mSv(P<0.05).The dosage of contrast agent in group A was significantly lower than that in group B[(73.97±12.15)mL in group A,(82.50±2.61)mL in group B](P<0.05).Conclusion Low-dose test method combined with VHP technology not only can reduce the radiation dose and contrast agent dosage,but also can effectively improve the success rate and image quality of lower extremity arteries examination,which is worthy of clinical application.

5.
Article in Chinese | WPRIM | ID: wpr-1023985

ABSTRACT

Objective:To investigate the iodine nutrition status of key population in Fuzhou City, and to provide scientific basis for adjusting intervention strategies.Methods:From March to October 2021, a survey was conducted on iodine nutrition status of key population in 12 counties (cities, districts) of Fuzhou City. Each county (city, district) was divided into 5 sampling areas according to the east, west, south, north and middle directions. One township (street) was selected from each area, and 40 non-boarding children aged 8 - 10 (age balanced, half male and half female) from one primary school and 20 pregnant women (early, middle and late pregnancy balanced) were selected as survey subjects. Household salt samples and random urine samples were collected, and the salt iodine and urine iodine levels were tested by direct titration and arsenic and cerium catalytic spectrophotometry, respectively. Children's thyroid volume was measured by B-ultrasonography. At the same time, in cooperation with Fuzhou Maternal and Child Health Hospital, the thyroid stimulating hormone (TSH) testing results of heel blood of full-term natural delivery newborns in Fuzhou City in 2021 were collected.Results:A total of 2 400 children were monitored for salt iodine, urine iodine and goiter. The median salt iodine was 24.40 mg/kg, with an iodine salt coverage rate of 93.04% (2 233/2 400), a qualified rate of iodized salt of 97.40% (2 175/2 233), and a consumption rate of qualified iodized salt of 90.62% (2 175/2 400). The median urine iodine was 181.47 μg/L. The rate of goiter was 1.04% (25/2 400). A total of 1 200 pregnant women were monitored for salt iodine and urine iodine. The median salt iodine was 24.10 mg/kg, the coverage rate of iodized salt was 91.08% (1 093/1 200), the qualified rate of iodized salt was 97.90% (1 070/1 093), and the consumption rate of qualified iodized salt was 89.17% (1 070/1 200). The median urine iodine was 128.10 μg/L. The median TSH level in the heel blood of 14 242 newborns was 3.38 mU/L, and the proportion of TSH level > 5 mU/L was 30.96% (4 410/14 242).Conclusions:In 2021, children in Fuzhou City are at an appropriate level of iodine, but pregnant women are insufficient of iodine. We should continue to maintain comprehensive prevention and control measures mainly based on salt iodization, provide health education for pregnant women, and strengthen monitoring of TSH level in newborns.

6.
Article in Chinese | WPRIM | ID: wpr-1024058

ABSTRACT

Objective To study the effect of silica in soil on the extraction of biological evidence DNA at the crime scene using the silica bead method.Methods Mud suspension and diluted blood were mixed to prepare biological samples mixed with dust and soil,which is to simulate biological evidence at the crime scene.Cell lysis was performed using heating lysis and guanidine salt chemical lysis,respectively.DNA was extracted using the silica bead method,amplified by PCR using Identifiler Plus kit and detected by capillary electrophoresis.The electrophoresis results were compared.Using mud suspension instead of silica beads to extract diluted blood DNA to validate the effect of silica in soil on the extraction of biological evidence DNA at crime scene using silica beads method.Results The complete STR loci were obtained after the extraction and amplification of 4 μL,20 μL dilute blood mixed with mud and lysed with heating cracking,whoes average peak heights arel 969.7±376.9 RFU and 9 706.7±349.8 RFU.For the 4 μL dilute blood mixed with mud guanidine salt chemical lysis,it cannot obtain complete STR loci after extraction and amplification.20 μL dilute blood mixed with mud guanidine salt was chemically cleaved and amplified to obtain complete STR loci with an average peak height of 1 899.8±801.3 RFU.After extraction and amplification by mud suspension instead of silica beads to extract 20 μL diluted blood DNA,complete STR loci were obtained.Conclusion Silicon dioxide in soil can bind to DNA in the presence of guanidine salts,leading to a decrease in the efficiency of recovering on-site biological evidence DNA using the silicon bead method.

7.
Chinese Journal of Immunology ; (12): 122-126, 2024.
Article in Chinese | WPRIM | ID: wpr-1024727

ABSTRACT

Objective:To investigate whether IL-7-secreting oncolytic herpes simplex virus(HSV)could activate CD8+T cells and inhibit the growth of hepatocellular carcinoma.Methods:The expression of IL-7 was detected by Western blot.The in vitro cleavage of tumor cells by tumor oncolytic virus HSV and HSV-IL-7 were detected by crystal violet staining.The tumor inhibition ability of HSV-IL-7 and HSV were detected in subcutaneous transplanted tumor model.Levels of IL-7,IFN-γ and TNF-α in serum and tumor tissues were determined by ELISA.The infiltration of CD8+T cells in tumor tissues was detected by immunohistochemistry.Flow cytometry was used to detect Granzyme B secretion in CD8+T cells infiltrated by tumor.Results:Tumor cells infected with HSV-IL-7 expressed high level of IL-7.Both HSV and HSV-IL-7 can effectively lyse B16-F10,CT-26 and H22 tumor cell lines in a dose-dependent manner in vitro.HSV-IL-7 could significantly inhibit the growth of H22 hepatoma cells in vivo(P<0.01)and prolong the survival time of tumor-bearing mice(P<0.001).HSV-IL-7 could significantly increase the IL-7 content in tumor sites(P<0.000 1),and effectively increase the number of tumor infiltrating CD8+T cells(P<0.001).HSV-IL-7 significantly enhanced Granzyme B secretion of tumor-infiltrating CD8+T cells and IFN-γ and TNF-α in tumor tissues(P<0.000 1).Conclusion:HSV-IL-7 has well tumor inhibition activity in vivo and in vitro.It also can activate the anti-tumor activity of CD8+T cells in vivo by secreting IL-7,inhibit tumor growth and prolong the survival time of tumor-bearing mice.

8.
Article in Chinese | WPRIM | ID: wpr-1025409

ABSTRACT

Objective:To analyze the clinicopathological features of gastric oxyntic gland neo-plasms.Methods:Forty-nine cases of stomach oxyntic gland neoplasms including oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG)diagnosed in the Sec-ond Hospital of Shandong University from January 2016 to December 2020 were selected.The clini cal information,endoscopic appearance,histological features and immunophenotype were analyzed retrospectively,and followed up.Results:Age of the gastric oxyntic gland neoplasm patients ranged from 19 to 83 years old,with an average age of(57.3±2.4)years old.The male-to-female ratio was 24:25.Most of the lesions were located in the gastric body(27/49)and fundus(15/49).There were four endoscopic phenotypes:flat bulging,polypoid,flat and depression.In some lesions,there were dilated dendritic vessels.48 cases were single onset.The mean maximum diameter of lesions was(3.9±0.5)mm(1.0~7.0 mm).Seven cases showed submucosal invasion,and the inva-sion depth was less than 500 μm.The tumor consists of the dense glandular and the glandular con-nects to form a strip shape,which is irregularly branched and labyrinthlike under the microscope.These tumor cells were well differentiated and the morphology was similar to oxyntic gland cells.The chief cells were the predominant cells.The nucleus was mildly enlarged with slight pleomorphism and the mitosis was uncommon.The oxyntic gland neoplasms of the stomach were diffusely posi-tive for Mucin-6(MUC6)(100%)and Pepsinogen Ⅰ(83%),focally positive for H+/K+-ATPase(58%).Conclusions:The stomach oxyntic gland neoplasm is a new histology type with unique clinico-pathological features.The incidence of this neoplasm is low and the prognosis is good but it still needs long-term follow-up.

9.
Article in Chinese | WPRIM | ID: wpr-1039129

ABSTRACT

Magnetic cell sorting technology is a highly specific and rapid cell sorting technology using superparamagnetic nanocomposites for cell sorting, which is widely used in immunology, stem cytology, oncology, clinical medicine and other fields. Magnetic cell sorting technology is divided into positive isolation, negative isolation/untouched cell isolation, depletion, multi-step isolation and automated cell separation systems. In this review, we firstly give a brief introduction to the classification and application of magnetic cell sorting technology, then discuss several new techniques and challenges based on magnetic cell sorting in recent years, such as improving the sorting efficiency by improving the structure of magnetic materials and magnetic field structure. The necessity of biological evaluation of magnetic cell sorting products was emphatically analyzed. Through the biological evaluation, the advantages and disadvantages of magnetic cell sorting products can be understood, and the research and development ability could be improved. Therefore, 10 biological evaluation technical parameters related to magnetic cell sorting products were proposed: yield, purity, sterility, cytotoxicity, cell morphology, viability, light scattering characteristics of cells, fluorescent antibody labeling ability of cells, cell activation and cell proliferation. The 10 biological evaluation technical parameters play an important role in promoting the standardized application of magnetic cell sorting.

10.
Chinese Medical Ethics ; (6): 206-210, 2024.
Article in Chinese | WPRIM | ID: wpr-1012877

ABSTRACT

In order to build a global community of health for all, it is necessary to deeply understand the influencing factors of cross-cultural communication between medical professionals and patients. Factors such as different health beliefs, cultural values and communication mediators influence cross-cultural communication between medical professionals and patients, and then affect the medical satisfaction and treatment compliance. Medical education should adopt the learning concept of constructivism, advocate maintaining a humble cultural attitude, incorporate more patient perspectives and adopt cross-cultural teaching mode to improve the cross-cultural communication competence of medical students and medical staff, so as to establish a relationship based on communication and understanding.

11.
Chinese Medical Ethics ; (6): 649-653, 2024.
Article in Chinese | WPRIM | ID: wpr-1012956

ABSTRACT

Ethical sensitivity is a behavioral concept emerging in recent years, which has attracted high attention from all sectors of society. Ethical sensitivity not only affects the clinical decision-making, doctor-patient relationship and medical quality of medical staff, but also provides the possibility to identify, predict and solve ethical problems in clinical. Combined with previous studies, this paper analyzed the current situation of ethical sensitivity of medical personnel in China, and took pediatric medical staff as an example to analyze the factors affecting the ethical sensitivity of medical staff from clinical practice and related theories, including age, working years, occupational categories, education level, work environment, empathy ability, etc. At the same time, this paper analyzed the causes of the ethical sensitivity of medical staff from the perspective of clinical practice and related systems, and put forward corresponding countermeasures, so as to improve the ethical sensitivity of medical staff and help to build a harmonious doctor-patient relationship.

12.
Chinese Journal of Nursing ; (12): 461-464, 2024.
Article in Chinese | WPRIM | ID: wpr-1027869

ABSTRACT

To summanze the nursing points of enterostomy among 6 children with small intestinal transplantation,which could provide references for clinical nursing.Key points:to set up a multidisciplinary team and develop an observation plan about enterostomy;to monitor the blood circulation of enterostomy closely,so as to identify the vascular complications as soon as possible;to closely observe the excrement of enterostomy and being vigilant for rejection reaction;to select reasonable nursing supplies based on the situation of enterostomy;to treat the abdominal incision fluid leakage timely,and pay attention to protect the skin around the enterostomy and take measures to control infection;furthermore,to attach great importance to continuous nursing care and improve the quality of home care.After above careful treatment,all the 6 children survived;they were discharged from hospital 3~4 months later after the operation of enterostomy restoration.Followed up 2~4 months,6 children recovered well.

13.
Article in Chinese | WPRIM | ID: wpr-1018678

ABSTRACT

Objective To explore the pattern of early expression and secretion of tissue factor(TF)in vascular endothelial cells induced by heat stress.Methods Thirty SPF-rated C57BL/6 male mice were randomly divided into five groups:the control group and groups of indicated recovery time,including 0,3,6,and 9 h in room temperature after heat stress(n=6).Mice in the heat stress groups were exposed to an animal incubator to reach 42.5℃for core body temperature for heat stroke.We analyzed the histopathological changes in the liver,lung,and kidney tissues with HE staining.We measured the TF mRNA in mice tissues by RT-qPCR and the plasma concentration of TF in mice with a commercial ELISA kit.Human umbilical vein endothelial cells(HUVECs)were placed in a culture incubator to build an in vitro heat stress model.HUVECs were divided into five groups,including a control group and groups of indicated recovery time,including 0,3,6,and 9 h after heat stress.We quantified the expression of TF mRNA and protein in HUVEC cells by RT-qPCR,Western blotting,and immunofluorescence and measured the secreted TF with a commercial ELISA kit.Results No significant pathological injury was observed in the tissues of the control group.Mice treated with heat stress had various degrees of structural injuries and hemorrhagic and inflammatory changes in multiple tissues.Compared to control group,the expression of TF mRNA significantly increased in the kidney of heat stress-treated mice with 0 and 3 h recovery time(1.719±0.018,1.241±0.178 vs.1.000±0.063),the lung with 3 h recovery time(2.444±0.511 vs.1.000±0.106)and the liver with 6 h recovery time(7.312±0.618 vs.1.000±0.147)(P<0.05).The concentration of TF in plasma also sustainedly elevated in mice with 0,3,6,and 9 h recovery time after heat stress as compared to control group[(132.426±17.920)pg/ml,(119.400±10.267)pg/ml,(107.374±13.495)pg/ml,(163.767±22.810)pg/ml vs.(75.479±13.831)pg/ml,respectively,P<0.01].The expression levels of TF mRNA were higher in heat stress HUVECs with 6 h and 9 h recovery time than the control cells(1.905±0.354,2.564±0.297 vs.1.000±0.097,P<0.01).Secreted TF in the supernatant from HUVECs treated with heat stress and different recovery time also increased significantly[(36.309±4.101)pg/ml,(38.425±5.484)pg/ml,(41.655±4.380)pg/ml,(43.586±4.718)pg/ml vs.(14.996±0.254)pg/ml,P<0.01].Conclusion Heat stress increased early expression and secretion of TF in vascular endothelial cells.Vascular endothelial cells may be a main source of circulating TF in heat stroke.

14.
Article in Chinese | WPRIM | ID: wpr-1020288

ABSTRACT

Objective:To summarize the nursing experience of liver transplantation in a patient with acute liver failure, renal injury, shock, hepatic encephalopathy and hyperlactic acidemia caused by K-amine poisoning.Methods:A case of severe K-amine poisoning admitted to the First Affiliated Hospital of Zhejiang University Medical College on June 29, 2022 was treated by multidisciplinary team cooperation. The treatment scheme of blood purification combined with liver transplantation was adopted, individualized nursing measures were implemented, including fluid resuscitation, blood purification, prevention and treatment of complications such as brain edema and infection of hepatic encephalopathy, immunosuppressive treatment after liver transplantation, occupational protection, health education and follow-up management.Results:After careful treatment and nursing, the liver and kidney function of the patient recovered smoothly and was discharged on the 33rd day after liver transplantation.Conclusions:In view of the rapid progress of acute liver failure caused by K-amine poisoning and the involvement of multiple organs, blood purification combined with liver transplantation successfully saved the lives of patients under the cooperation of multidisciplinary teams. Do a good job in disease monitoring and individualized nursing to improve the long-term survival rate of patients.

15.
Article in Chinese | WPRIM | ID: wpr-1024074

ABSTRACT

Sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infections.Platelet-related indicators are closely related to the prognosis of sepsis,including platelet(PLT)count,mean plate-let volume(MPV),platelet distribution width(PDW)and platelet aggregation rate(PAR),which can serve as im-portant evaluation indicators for the occurrence and development of sepsis.This paper elaborates the value of plate-let-related indicators in evaluating the prognosis of patients with sepsis,aiming to help clinicians understand the clinical value of monitoring platelet-related indicators in sepsis patients and accurately identify high-risk sepsis pa-tients.

16.
Article in Chinese | WPRIM | ID: wpr-1008651

ABSTRACT

The human use experience of traditional Chinese medicine(TCM) is of great significance for the development of new traditional Chinese medicine. In 2023, the National Medical Products Administration(NMPA) issued the Special Regulations on Registration Management of Traditional Chinese Medicine, which explicitly encouraged the conduct of high-quality human use experience research on TCM clinical practice to obtain sufficient evidence for registration support. It also required that human use experience research should comply with relevant requirements and undergo registration verification. The quality of human use experience research on TCM directly determines the reliability of the evidence. This article discussed the quality requirements for human use experience research on TCM from the perspectives of basic requirements, organizational management, key pharmaceutical information, scientific research, risk management, ethical compliance, and study implementation and proposed differential treatment in quality requirements and registration verification focus based on different research purposes, stages, and types of studies. While ensuring the authenticity of data, retrospective studies should pay particular attention to the integrity of the data, and prospective studies should focus on the normativity of the data, which may affect the research conclusions. Human use experience research, as part of drug registration materials, falls within the scope of relevant regulatory oversight. Researchers should have a strong awareness of regulations to avoid serious quality issues. The standardized conduct of human use experience research on TCM requires joint efforts from regulatory authorities, applicants, research institutions, and researchers to establish a research quality management system based on the clinical characteristics of TCM.


Subject(s)
Humans , Medicine, Chinese Traditional , Prospective Studies , Reproducibility of Results , Retrospective Studies , Pharmaceutical Preparations , Drugs, Chinese Herbal/therapeutic use
17.
Article in English | WPRIM | ID: wpr-1007879

ABSTRACT

OBJECTIVE@#To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.@*METHODS@#Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice.@*RESULTS@#DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA).@*CONCLUSION@#DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.


Subject(s)
Animals , Mice , Alzheimer Disease/therapy , AMP-Activated Protein Kinases/metabolism , Amyloid beta-Protein Precursor/metabolism , Antioxidants/metabolism , Disease Models, Animal , Hippocampus/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Mammals/metabolism , Mice, Inbred C57BL , Mice, Transgenic , NF-E2-Related Factor 2/metabolism , Presenilin-1/metabolism , TOR Serine-Threonine Kinases/metabolism
18.
Acta Pharmaceutica Sinica ; (12): 2541-2550, 2023.
Article in Chinese | WPRIM | ID: wpr-999003

ABSTRACT

As an important component of nucleosomes on the chromatin of eukaryotic cells, histones play an important role in the development and progression of tumour diseases by regulating epigenetic post-translational modifications such as acetylation and methylation. In addition, development of inhibitors targeting methyltransferase and deacetylase provides novel therapeutic strategies for cancer treatment. Mass spectrometry-based proteomics can reveal the global changes of histone modifications under the action of drugs during disease progression, which in turn provides important support for revealing drug action mechanism, drug resistance mechanism, and investigating novel drug combination strategies. This article focuses on the progress and status of proteomic research on a variety of histone modifying enzyme inhibitors, including methyltransferase inhibitors and histone deacetylase inhibitors, which will help to understand the current and further utilization of proteomics in studying histone modifications.

19.
Acta Pharmaceutica Sinica ; (12): 1267-1274, 2023.
Article in Chinese | WPRIM | ID: wpr-978705

ABSTRACT

Using beta-2 adrenergic receptor, 5-hydroxytryptamine and angiotensin II type 1 receptor as control, we here established a method for rapid prediction of the initial position amino acids of N-terminal, C-terminal, intracellular loops, extracellular loops and transmembrane (TM) regions in G protein-coupled receptors (GPCRs), and successfully predicted the structure of Mas-related G protein-coupled receptors X3 (MRGPRX3). To achieve this purpose, nanoluciferase (Nluc) was inserted into the different sites of these GPCRs′ sequence by sequence and ligation-independent cloning (SLIC) method, and the luminescence value were measured to distinguish the different parts of GPCRs. The results showed that luminescence values of NLuc luciferase at TM region were less than 100 000, and the values were higher than 1 000 000 at N terminal, C terminal, or extracellular loops and intracellular loops, and the values were between 100 000 and 500 000 at junction. The predicted MRGPRX3 structure was analyzed in detail and was compared with AlphaFold predicted structure. In conclusion, this method could provide useful information of GPCR structure model for the ligand virtual screening, and could provide certain experimental basis for structural pharmacology.

20.
China Tropical Medicine ; (12): 353-2023.
Article in Chinese | WPRIM | ID: wpr-979685

ABSTRACT

@#Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with <ULN accounted for 32.38%, 35.03% and 36.07% of significant liver tissue injury, respectively. And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%, 41.85% and 50.30%, respectively. The optimal ALT critical values were 33 U/L for overall patients, 25 U/L for females, 45 U/L for males, 45 U/L for ≤30 years olds, 33 U/L for>30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.

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