Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 377
Filter
1.
Cancer Med ; 13(12): e7388, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38924330

ABSTRACT

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate , Biliary Tract Neoplasms , Biomarkers, Tumor , ROC Curve , Humans , Male , Female , Middle Aged , Biliary Tract Neoplasms/diagnosis , Biliary Tract Neoplasms/blood , Antigens, Tumor-Associated, Carbohydrate/blood , Biomarkers, Tumor/blood , Aged , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/blood , Liver Neoplasms/diagnosis , Liver Neoplasms/blood , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/blood , CA-19-9 Antigen/blood , Retrospective Studies , Sensitivity and Specificity
2.
Mol Med Rep ; 30(2)2024 08.
Article in English | MEDLINE | ID: mdl-38873983

ABSTRACT

Chronic obstructive pulmonary disease (COPD) exacerbations accelerate loss of lung function and increased mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations. The present study aimed to assess the metabolic characteristics of the frequent exacerbation of COPD (COPD­FE) phenotype, identify potential metabolic biomarkers associated with COPD­FE risk and evaluate the underlying pathogenic mechanisms. An internal cohort of 30 stable patients with COPD was recruited. A widely targeted metabolomics approach was used to detect and compare serum metabolite expression profiles between patients with COPD­FE and patients with non­frequent exacerbation of COPD (COPD­NE). Bioinformatics analysis was used for pathway enrichment analysis of the identified metabolites. Spearman's correlation analysis assessed the associations between metabolites and clinical indicators, while receiver operating characteristic (ROC) analysis evaluated the ability of metabolites to distinguish between two groups. An external cohort of 20 patients with COPD validated findings from the internal cohort. Out of the 484 detected metabolites, 25 exhibited significant differences between COPD­FE and COPD­NE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman's correlation analysis demonstrated associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis demonstrated that the area under the curve (AUC) values for D­fructose 1,6­bisphosphate (AUC=0.871), arginine (AUC=0.836), L­2­hydroxyglutarate (L­2HG; AUC=0.849), diacylglycerol (DG) (16:0/20:5) (AUC=0.827), DG (16:0/20:4) (AUC=0.818) and carnitine­C18:2 (AUC=0.804) were >0.8, highlighting their discriminative capacity between the two groups. External validation results demonstrated that DG (16:0/20:5), DG (16:0/20:4), carnitine­C18:2 and L­2HG were significantly different between patients with COPD­FE and those with COPD­NE. In conclusion, the present study offers insights into early identification, mechanistic understanding and personalized management of the COPD­FE phenotype.


Subject(s)
Biomarkers , Metabolomics , Phenotype , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/blood , Male , Female , Metabolomics/methods , Aged , Biomarkers/blood , Middle Aged , ROC Curve , Metabolome , Disease Progression , Carnitine/blood , Carnitine/analogs & derivatives
4.
World J Gastrointest Oncol ; 16(2): 331-342, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38425385

ABSTRACT

BACKGROUND: Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM: To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS: A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS: Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION: In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-999163

ABSTRACT

ObjectiveTo investigate the effect of Gegen Qinliantang on glucose and lipid metabolism in the rat model of catch-up growth (CUG) induced by a high-fat diet and the underlying mechanism. MethodA total of 60 SD rats were randomized into a normal control group (n=18) and a modeling group (n=42). The rat model of CUG was established with a restricted diet followed by a high-fat diet, and the changes of general status and body weight were observed. The levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), and total cholesterol (TC) were measured in 6 rats in each group at the end of the 4th and 8th week, respectively. The homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated, and the insulin sensitivity and body composition changes of CUG rats were evaluated. The successfully modeled rats were assigned into 6 groups: normal control, model, high-, medium-, and low-dose Gegen Qinliantang (2.5, 5, 10 g·kg-1), and pioglitazone (3.125 mg·kg-1). The rats were administrated with corresponding drugs by gavage for 6 weeks, and the normal control group and model group were administrated with the same amount of normal saline. During the experiment period, the changes of body weight were recorded, and the FBG, FINS, HOMA-IR, TG, and TC were determined at the end of the experiment. Hematoxylin-eosin (HE) staining was employed to observe the pathological changes of skeletal muscle in rats. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the skeletal muscle were measured strictly according to the manuals of the reagent kits. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was performed to measure the mRNA levels of silencing information regulator 1 (SIRT1), peroxisome proliferator-activated receptor-gamma coactivator1α (PGC1α), and nuclear respiratory factor 1 (Nrf1) in the skeletal muscle. Western blot and immunohistochemistry were employed to assess the expression of SIRT1, PGC1α, and Nrf1 in the skeletal muscle. ResultCompared with the normal control group, the model group presented elevated levels of FBG, FINS, TG, and TC (P<0.05, P<0.01), increased HOMA-IR (P<0.01), increased diameter of muscle fibers and adipocytes between muscle cells in the skeletal muscle, rising levels of ROS and MDA in the skeletal muscle (P<0.01), and down-regulated mRNA and protein levels of SIRT1, PGC1α, and Nrf1 (P<0.05, P<0.01). Compared with the model group, Gegen Qinliantang (especially the medium and high doses) and pioglitazone decreased the body weight, FINS, HOMA-IR, and TG (P<0.05, P<0.01) and reduced interstitial components such as intermuscular fat in the skeletal muscles and the diameter of muscle fibers. Furthermore, the drugs lowerd the levels of ROS and MDA (P<0.05, P<0.01) and up-regulated the mRNA and protein levels of SIRT1, PGC1α, and Nrf1 (P<0.05, P<0.01) in the skeletal muscle. ConclusionGegen Qinliantang can ameliorate the glucose and lipid metabolism disorders and insulin resistance in CUG rats by regulating the SIRT1/PGC1α/Nrf1 signaling pathway.

6.
Chemistry ; 29(56): e202301865, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37470691

ABSTRACT

Alzheimer's disease (AD) continues to be a major global health challenge, and the recent approval of Aduhelm and Leqembi has opened new avenues for its treatment. Small-molecule inhibitors targeting Aß aggregation hold promise as an alternative to monoclonal antibodies. In this study, we evaluated the ability of berbamine hydrochloride (BBMH), a member of the bisbenzylisoquinoline alkaloids, to reduce Aß aggregation and cytotoxicity. Thioflavin T kinetics, circular dichroism spectroscopy, and atomic force microscopy results indicated that BBMH effectively inhibited Aß aggregation. Surface plasmon resonance and molecular docking results further revealed that BBMH could bind to Aß fibrils, thereby hindering the aggregation process. This physical picture has been confirmed in a quantitative way by chemical kinetics analysis, which showed BBMH tends to bind with the fibril ends and thus prevents the transition from protofibrils to mature fibrils as well as the elongation process. Additionally, our MTT results showed that BBMH was able to reduce the cytotoxicity of Aß40 on N2a cells. Our results demonstrate, for the first time, the potential of BBMH to inhibit Aß aggregation and cytotoxicity, offering a promising direction for further research and drug development efforts in the fight against Alzheimer's disease.


Subject(s)
Alzheimer Disease , Benzylisoquinolines , Humans , Amyloid beta-Peptides/chemistry , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Molecular Docking Simulation , Peptide Fragments/toxicity , Peptide Fragments/chemistry , Benzylisoquinolines/pharmacology , Amyloid/chemistry
7.
Environ Toxicol ; 38(6): 1445-1454, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36929865

ABSTRACT

Bisphenol AF (BPAF), an emerging environmental endocrine disruptor, has been detected in surface waters worldwide and has adverse effects on aquatic organisms. The accumulation of BPAF in oceans and its potential toxic effect on marine organisms are important concerns. In this study, the effects of BPAF (10, 100, 1, and 5 mg/L) on marine medaka (Oryzias melastigma) were evaluated, including effects on the survival rate, heart rate, hatchability, morphology, and gene expression in embryos. The survival rate of marine medaka embryos was significantly lower after treatment with 5 mg/L BPAF than in the solvent control group. Exposure to 1 mg/L and 5 mg/L BPAF significantly reduced hatchability. Low-dose BPAF (10 µg/L) significantly accelerated the heart rate of embryos, while high-dose BPAF (5 mg/L) significantly decreased the heart rate. BPAF exposure also resulted in notochord curvature, pericardial edema, yolk sac cysts, cardiovascular bleeding, and caudal curvature in marine medaka. At the molecular level, BPAF exposure affected the transcript levels of genes involved in the thyroid system (dio1, dio3a, trhr2, tg, and thra), cardiovascular system (gata4, atp2a1, and cacna1da), nervous system (elavl3 and gap43), and antioxidant and inflammatory systems (sod, pparß, and il-8) in embryos. These results indicate that BPAF exposure can alter the expression of functional genes, induce abnormal development, and reduce the hatching and survival rates in marine medaka embryos. Overall, BPAF can adversely affect the survival and development of marine medaka embryos, and BPAF may not be an ideal substitute for BPA.


Subject(s)
Oryzias , Water Pollutants, Chemical , Animals , Water Pollutants, Chemical/metabolism , Embryo, Nonmammalian , Aquatic Organisms , Embryonic Development , Phenols/pharmacology
8.
Signal Transduct Target Ther ; 8(1): 58, 2023 02 08.
Article in English | MEDLINE | ID: mdl-36750721

ABSTRACT

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Chemoembolization, Therapeutic/adverse effects , Chemoembolization, Therapeutic/methods , Cohort Studies , Liver Neoplasms/pathology , Molecular Targeted Therapy , Retrospective Studies
9.
Article in English | WPRIM (Western Pacific) | ID: wpr-968551

ABSTRACT

Objective@#During the lockdown of cities and home quarantine, media became the only way for people to conveniently get coronavirus disease-2019 (COVID-19)-related information. And media engagement was closely related to psychological outcomes. But fewer researchers took COVID-19-related posting behaviors into consideration. Therefore, the present study aimed at examining the differences in psychological outcomes between people who posted COVID-19-related content on social media and those who did not. @*Methods@#The present study included 917 participants (304 males, 613 females) who had answered the questionnaires of media engagement, positive affect, negative affect, depression, anxiety, stress, satisfaction with life, death anxiety, and meaning in life. @*Results@#Results of t-tests showed that the Post group had lower levels of negative affect, anxiety, stress, and death anxiety than the Not Post (Npost) group. Network comparison tests indicated that the Npost group’s network and the Post group’s network differed in global strength, two edge-weights, and node centrality indices. @*Conclusion@#The results indicated that more attention should be paid to people who did not post any COVID-19-related content, especially when they have higher levels of stress and depression to prevent comorbidities. And for people who posted content, more attention should be paid when they have a higher level of negative affect.

10.
Asian Journal of Andrology ; (6): 85-90, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1009803

ABSTRACT

The clinical applications of acrosin activity are limited. We analyzed 61 578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between August 2014 and December 2019 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men; to determine whether correlations exist between acrosin activity and age, sperm concentration, sperm morphology, or sperm motility; and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the clinic. The cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 24.78 μIU per 106 sperm. There was no significant association between acrosin activity and age, sperm concentration, semen volume, total sperm count, progressive motility, or total motile spermatozoa. A weak positive correlation was found between acrosin activity and normal sperm morphology. There was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity (>24.78 μIU per 106 sperm) and the group with low acrosin activity (<24.78 μIU per 106 sperm). The group with a low IVF fertilization rate had a high index of abnormal acrosomal morphology at 21.2%, while the group with a high IVF fertilization rate had a low index of 0.2%. At an acrosin activity of <24.78 µIU per 106 sperm, in one cycle of the same patient, the fertilization rate, normal fertilization rate, and good-quality embryo rate for ICSI were significantly higher than those for IVF. Therefore, the most promising application of acrosin activity could be in the selection of ICSI over IVF for infertile male patients with complete fertilization failure or a low fertilization rate.

11.
Acta Pharmaceutica Sinica B ; (6): 2628-2644, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-982866

ABSTRACT

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

12.
Chinese Herbal Medicines ; (4): 407-420, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-982510

ABSTRACT

OBJECTIVE@#Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury.@*METHODS@#PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments.@*RESULTS@#Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3.@*CONCLUSION@#Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

13.
Asian Journal of Andrology ; (6): 350-355, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-981954

ABSTRACT

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.


Subject(s)
Humans , Male , Consanguinity , Pakistan , Infertility, Male/metabolism , Semen/metabolism , Sperm Tail/metabolism , Spermatozoa/metabolism , Flagella/pathology , Mutation
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-971499

ABSTRACT

OBJECTIVE@#To investigate the mechanism of shikonin-induced death of human hepatocellular carcinoma SMMC-7721 cells.@*METHODS@#Cultured SMMC-7721 cells and normal hepatocytes (L-02 cells) were treated with 4, 8, or 16 μmol/L shikonin, and the changes in cell viability was assessed using MTT assay. The levels of ATP and lactic acid in the cell cultures were detected using commercial kits. Co-immunoprecipitation and immunofluorescence staining were used to determine the relationship among pyruvate kinase M2 (PKM2), prolyl hydroxylase 3 (PHD3), and hypoxia-inducible factor-1α (HIF-1α). The expressions of PHD3, PKM2, HIF-1α, Bax, cleaved caspase-3, and Bcl-2 in SMMC-7721 cells were detected with Western blotting, and cell apoptosis was analyzed with annexin V-FITC/PI staining. The effects of RNA interference of PKM2 on PHD3 and HIF-1α expressions in SMMC-7721 cells were detected using Western blotting.@*RESULTS@#The IC50 of shikonin against SMMC-7721 and L-02 cells was 8.041 μmol/L and 31.75 μmol/L, respectively. Treatment with shikonin significantly inhibited the protein expressions of PKM2, HIF-1α and PHD3 and nuclear translocation of PKM2 and HIF-1α in SMMC-7721 cells. Coimmunoprecipitation and immunofluorescence staining confirmed that shikonin inhibited the formation of PKM2/PHD3/HIF-1α complex and significantly reduced the contents of lactic acid and ATP in SMMC-7721 cells (P < 0.05). The expressions of PHD3 and HIF-1α decreased significantly after PKM2 knockdown (P < 0.05). Shikonin treatment significantly increased the apoptosis rate, enhanced the expressions of Bax and cleaved caspase-3, and decreased Bcl-2 expression in SMMC-7721 cells (P < 0.05).@*CONCLUSIONS@#Shikonin induces apoptosis of SMMC-7721 cells possibly by inhibiting aerobic glycolysis through the PKM2/PHD3/HIF-1α signaling pathway to cause energy supply dysfunction in the cells.


Subject(s)
Humans , Prolyl Hydroxylases , Carcinoma, Hepatocellular , Caspase 3 , bcl-2-Associated X Protein , Liver Neoplasms , Signal Transduction , Apoptosis , Adenosine Triphosphate
15.
Acta Pharmaceutica Sinica ; (12): 2085-2097, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-999152

ABSTRACT

Macrophage migration inhibitory factor (MIF) is an enzyme-active pleiotropic cytokine that is expressed in various immune cells and tumor cells. MIF plays diverse roles in inflammation and tumor progression. It acts as a cytokine involved in immune response and inflammatory lesions. Additionally, MIF is closely associated with tumor proliferation, metastasis, and other tumor hallmarks, exerting a multifaceted influence on tumor occurrence and progression. MIF not only functions by being secreted into the extracellular space as a cytokine but can also be localized within the cytoplasm and nucleus, exhibiting diverse biological functions. As MIF in promoting tumor progression becomes increasingly recognized, MIF-based therapeutic strategies have become a hot research topic in oncology. Here, we provide a comprehensive review of MIF with different subcellular localization about their pro-tumoral functions. A better understanding of MIF in tumor biology will bring broader perspectives for the development of novel MIF targeting strategies and give promising direction for future tumor treatments.

16.
Acta Pharmaceutica Sinica ; (12): 3198-3203, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-999087

ABSTRACT

A flavoring agent and a suspension agent were prepared for extemporaneous compounding. The stability of the two agents before and after drug loading was investigated, and the taste of the suspension after extemporaneous compounding was evaluated by electronic tongue technology. The two agents remained stable under the conditions of influence factor test, accelerated test and long-term test. The appearance properties of the two agents did not change. The relative density of the flavoring agent was maintained at 1.053-1.075, and the pH was stable at 4.2-4.5. The relative density of the suspension agent was maintained at 0.999-1.022, and the pH was stable at 4.0-4.5. Seven kinds of drugs, including warfarin sodium tablets and spironolactone tablets, were mixed with these two oral solvents, and the content uniformity and stability were detected respectively. The results showed that the preparations could be evenly dispersed and the physical and chemical properties were stable. The results of taste evaluation showed that in captopril group and chloral hydrate group, the flavoring agent had the best effect on taste correction. In warfarin sodium group, rifampicin group, spironolactone group, vitamin B1 group and vitamin B2 group, the blending agents had the best effect on taste correction.

17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-971868

ABSTRACT

ObjectiveTo observe the effect of transcranial direct current stimulation (tDCS) on motor function of upper limbs of stroke patients with hemiplegia. MethodsFrom October, 2020 to October, 2021, 65 patients from Wuhan No.1 Hospital were randomly divided into control group (n = 32) and observation group (n = 33). All the patients received routine rehabilitation and mirror therapy, and the observation group received tDCS in addition, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT) and modified Barthel index (MBI) before and after treatment. ResultsThe scores of FMA-UE, ARAT and MBI improved in the both groups after treatment (|t| > 10.455, Z = -2.793, P < 0.001), and all the scores were better in the observation group than in the control group (|t| > 4.152, Z = -2.045, P < 0.05). ConclusionThe combination of tDCS can effectively promote the recovery of upper limb motor function of stroke patients.

18.
Sichuan Mental Health ; (6): 396-401, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-998144

ABSTRACT

BackgroundThe obsessive-compulsive disorder (OCD) features complexity in etiological factors and high heterogeneity in clinical manifestations. OCD patients with different ages of onset vary in clinical symptoms and etiology. However, current studies on inpatients with early- and late-onset OCD are limited. ObjectiveTo explore the differences in clinical characteristics between early- and late-onset OCD inpatients as well as the factors affecting the onset age of OCD, so as to provide references for early screening and treatment of OCD patients. MethodsThis study was based on collected medical records of 540 patients with OCD who received inpatient treatments at the Affiliated Brain Hospital of Nanjing Medical University between March 2012 and March 2023. Patients with onset age above 18 were placed into early-onset group (n=310) and the others into late-onset group (n=230). Then differences in demographic data and clinical symptoms between two groups of patients were compared. Binary logistic regression was used to analyze the factors that affect the onset age of OCD. ResultsObserving the demographic data, there were significant differences between the two groups in the results in gender, marital status, family history of mental illness, ratio of comorbidities with other mental illnesses, occupational composition, education level and types of obsessive-compulsive symptoms (χ2=22.302、170.556, 9.224, 13.624, 242.277, 59.791, 7.231, P<0.05 or 0.01). Also, the results in ages of onset and hospitalization between two groups were significantly different (Z=-19.915, 16.831, P<0.01). In terms of clinical symptoms, the early onset group had a higher proportion of symptoms including obsessive thinking (χ2=11.998, P<0.05), ordering (χ2=7.731, P<0.05) and rituals (χ2=7.714, P<0.05), while the proportion of obsessive checking (χ2=8.204, P<0.05) and washing (χ2=7.506, P<0.05) symptoms were relatively low. In terms of risk factors, there were several independent risk factors that influence the onset age of OCD inpatients, including comorbid neurodevelopmental disorder, comorbid affective disorder, family history of schizophrenia and family history of affective disorder (OR=19.587, 1.830, 3.065, 4.431, P<0.05). Among them, comorbid neurodevelopmental disorder was the core influencing factor, and female gender was a protective factor for early-onset patients (OR=0.417, P<0.01). ConclusionThere are differences in demographic data and clinical symptom characteristics between early- and late-onset OCD inpatients, and comorbid neurodevelopmental disorder plays as a core risk factor affecting the onset age of OCD inpatients. [Funded by Jiangsu Province Key Research and Development Plan for Social Development Special Project(number, BE2021616) ; Jiangsu Province Social Development General Project (number, BE2022678); Key Project of Nanjing Medical Science and Technology Development Fund (number, ZKX20029)]

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-996823

ABSTRACT

ObjectiveTo compare the therapeutic effects of oral Chinese medicines (including Chinese patent medicines) on coronary artery disease (CAD) by the Bayesian network Meta-analysis. MethodThe randomized controlled trials of treating CAD with oral Chinese medicines were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, PubMed, Web of Science, Embase, and Cochrane Library from the inception to December 1, 2022. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included articles. The direct meta-analysis was performed to compare the performance of oral Chinese medicines alone and in combination with Western medicine in the treatment of CAD in terms of intima-media thickness (IMT), vascular endothelial function, plaque score, hypersensitive C-reactive protein (hs-CRP), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total response rate. Furthermore, the Bayesian network Meta-analysis was performed to compare the therapeutic effects of different Chinese medicines. ResultA total of 41 articles were included. The direct meta-analysis results showed that Chinese medicines combined with Western medicine outperformed Western medicine alone in recovering all the indicators of CAD. The Bayesian network meta-analysis yielded the following results. In terms of the total response rate, modified Huangqi Guizhi Wuwutang and Sanqi Huayu pills had obvious advantages over other Chinese medicines. In terms of IMT and plaque score, Xiaoban Huazhuo decoction, Yiqi Tongluo formula, Ruangan Jiangzhi capsules, and Guanxin Shutong capsules had obvious advantages over other Chinese medicines. In terms of blood lipid indicators, Shenqi Roumai mixture, Ruangan Jiangzhi capsules, Xiaoban Huazhuo decoction, Qiwei Sanxiong decoction, and Sanqi Huayu pills were superior to other Chinese medicines. The Chinese medicines above mainly had the functions of activating blood, resolving stasis, resolving phlegm, and dredging vessels. ConclusionThe combination of oral Chinese medicines and Western medicine is effective in treating CAD. Clinicians can use the drugs targeting abnormal indicators according to the results of this Bayesian network meta-analysis combined with the actual situation of patients to achieve better therapeutic effects.

20.
Journal of Chinese Physician ; (12): 714-718, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-992367

ABSTRACT

Objective:To evaluate the diagnostic evaluation process and the effectiveness and safety of intracavitary therapy for pelvic congestion syndrome (PCS).Methods:A retrospective analysis was conducted on 38 patients admitted to Beijing Shijitan Hospital affiliated to Capital Medical University from March 2019 to February 2022. Combined with the patient′s symptoms, PCS was diagnosed by color Doppler ultrasound, computed tomography venography (CTV), and venography. The ovarian vein was embolized with controllable spring coil and polydocanol foam sclerosing agent. The patients were followed up 1, 3 and 6 months after operation.Results:The total surgical success rate of 38 patients was 100%, and the incidence of complications was 5.3%(2/38); Spring coils (2.8±0.3)per person; The dosage of hardener was (7.0±2.1)ml/person. The improvement rate of patient symptoms was 97.4%(37/38); After 1, 3, and 6 months of surgery, color Doppler ultrasound was reexamined and no recanalization was observed in the embolized ovarian veins; The diameter of the parauterine vein was (2.8±0.5)mm, which was significantly lower than the preoperative (7.5±1.9)mm ( P<0.05); The Visual Analogue Scale (VAS) score was significantly lower than the preoperative score [(2.12±1.87)points vs (7.58±0.82)points, P<0.001]. Conclusions:Process based assessment is helpful in identifying and diagnosing PCS patients who urgently need treatment; Endovascular treatment based on embolization of ovarian vein with controllable spring coil and foam sclerosing agent is minimally invasive, safe and effective.

SELECTION OF CITATIONS
SEARCH DETAIL