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Objective To compare and analyze the disease burden caused by drinking in China in 1990 and 2019. Methods The global disease burden database 2019 was used to analyze the attribution score (PAF), mortality, disability adjusted life year (DALY) and other indicators attributed to drinking in China in 1990 and 2019. The disease burden caused by alcohol consumption was compared between China and the world as well as different social demographic index (SDI) regions. Results From 1990 to 2019, the PAF attributed to drinking increased by 12.85%. The number of deaths attributed to drinking increased to 514 700, and the mortality increased to 36.18/100 000, while the DALY attributed to drinking increased to 17.2651 million person-years, and the DALY rate increased by 5.16%. The disease burden attributed to drinking was higher in men than that in women, and the attributable mortality and DALY rate in the elderly over 70 years old were higher than those in the young. From 1990 to 2019, the attributable disease burden of esophageal cancer was the highest in China, followed by colorectal cancer. Compared with the world and different SDI regions, China had the lowest standardized DALY rate attributed to drinking. Conclusion Drinking is one of the important risk factors for related diseases and cancers in China, and effective intervention measures should be taken for key populations.
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In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl2 was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L-1 CoCl2 for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.
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Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.
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Humans , Adult , Hepatitis B, Chronic/complications , Retrospective Studies , Cross-Sectional Studies , Hepatitis B e Antigens , DNA, Viral , Antiviral Agents/therapeutic use , Hepatitis B virus/genetics , DemographyABSTRACT
BACKGROUND: Metal anchors are not easily accepted by patients as permanent foreign bodies, so bioabsorbable anchors have been gradually applied in orthopedics in recent years. OBJECTIVE: To evaluate the effectiveness of absorbable suture anchors for repairing femoroacetabular impingement syndrome combined with acetabular labral tears. METHODS: Eighty patients with femoroacetabular impingement syndrome combined with acetabular labral tears admitted in Beijing Shijitan Hospital Affiliated to Capital Medical University from February 2014 to February 2016 were selected, and all were treated by absorbable suture anchors under arthroscopy. The Harris hip score, and the Visual Analogue Scale score at baseline, postoperative 1 and 3 months were recorded and compared to assess the effectiveness. The complications and material-host reaction were recorded. The treatment satisfaction was evaluated. The study was approved by the Ethical Committee of Beijing Shijitan Hospital and all patients and their families signed the informed consents. RESULTS AND CONCLUSION: (1) The Harris hip scores at 1 and 3 years postoperatively in 80 patients with femoroacetabular impingement syndrome combined with acetabular labral tears were significantly higher than those at baseline, and the Visual Analogue Scale scores were significantly lower than those at baseline (P 0. 05). (3) None appeared with anchor drop off, cartilage injury or material-host reaction. In summary, the method of absorbable suture anchors under arthroscopy has the advantages of minimal invasion, reliable fixation, simple operation, no metal implants, and significant clinical effect to treat femoroacetabular impingement syndrome combined with acetabular labral tears.
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OBJECTIVE@#To establish a stable and rapidly rat model acquired aplastic anemia.@*METHODS@#The SD rats were exposed to Csγ-ray at 3.5 and 4.0 Gy ( 91 cGy/min), and intraperitoneally injected with CTX at 35 mg/( kg·d) and CHL at 45 mg/( kg·d) in d 4, 6 and 8 after irradiation; the WBC, platelet and reticulocyte counts in peripheral blood, the smears and nucleated cells counts of bone marrow were observed.@*RESULTS@#The levels of peripheral blood 3-lineage cells of SD rats treated with Csγ-irradiation combined with cyclophosphamide and chloramphenicol were significantly reduced, among which white blood cells, platelets and reticulocytes decreased rapidly, and the number of bone marrow nucleated cells decreased significantly; bone marrow pathological sections showed severe reduction of hematopoietic cells, and the non-hematopoietic cells such as fat cells increased, and a serve or lightly reduction of bone marrow cells were found.@*CONCLUSION@#The rat model established by Csγ-ray irradiation combined with cyclophosphamide and chloramphenicol meets the clinical characteristics of aplastic anemia, and this study provides a stable rat model for the study of new therapeutic drugs for acquired aplastic anemia.
Subject(s)
Animals , Rats , Anemia, Aplastic , Bone Marrow , Bone Marrow Cells , Cyclophosphamide , Rats, Sprague-DawleyABSTRACT
OBJECTIVE@#To improve and establish the mouse model with aplastic anemia (AA) mediated by Cs γ-ray irradiation combined with cyclophosphamide (CTX) and chloramphenicol (CHL) injection,so as to provide a stable model for studying the pathogenesis and treatment of AA .@*METHODS@#The BALB/c mice were exposed to Cs γ-ray of 3-5 Gy(91 cGy/min) and were intraperitoneally injected with CTX of 25 mg/(kg.d) and CHL of 62.5 mg/(kg.d) at D 4,5 and 6 after irradiation; the WBC, platelet and reticulocyte counts in peripheral blood as well as the mucleated cell count in bone marrow and bone marrow smears were detected .@*RESULTS@#The 3-lineage cells in peripheral blood of BALB/c mouse model with acquired AA were rapidly reduced, especially WBC, platelet and reticulocyte counts were lowest at D 14,the 3-lineage cells in peripheral blood were still severely reduced at D 28; the nucleated cell count in bone marrow significantly dcreased,the bone marrow hyperplasia was reduced or severely reduced; the pathological sections of bone marrow showed the severe reduction of hematopoietic cells and the increased of non-hematopoietic cells such as fat cells.@*CONCLUSION@#The mouse model with acquired AA has been established by Cs γ-ray irradiation combined with CTX and CHL injection. All detection indicators of this model reach to diagnostic criteria for acquired AA,therefore this mouse model may be used as the model for study of pathogenesis and treatment of acquired AA.
Subject(s)
Animals , Mice , Anemia, Aplastic , Chloramphenicol , Cyclophosphamide , Gamma Rays , Mice, Inbred BALB CABSTRACT
Objective: To observe the effect of diosgenin on aplastic anemia (AA) mice and peroxisome proliferator activated receptor γ (PPARγ), CCAAT-enhancer binding protein α (C/EBPα), Adiponectin, Leptin, in order to discuss the potential mechanism of bone marrow mesenchymal stem cells in the process of adipemia. Method: BALB/c mice were randomly divided into control group and model group. The model group was established by 60Coy irradiation combined with tail vein infusion with lymphatic suspension cells of DBA/2 mice. After successful evaluation of the model, the mice were randomly divided into 6 groups:model group, low, medium and high-dose diosgenin groups (37.44,74.88,149.76 mg·kg-1·d-1), cyclosporine group (23.5 mg·kg-1·d-1), and tripterygium glycoside group (9.36 mg·kg-1·d-1), and given corresponding drugs by gavage for 14 days. After the intervention, the peripheral blood of mice in each group was detected, and bone marrow smears were collected to evaluate the proliferation of bone marrow. Bone marrow mesenchymal stem cells (BMMSCs) were isolated and cultured by adherent method and induced by adipogenesis. The mRNA and protein expressions of PPARγ, C/EBPα, Adiponectin, Leptin in BMMSCs were detected by quantitative real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result: The white blood cell (WBC), hemoglobin (HGB) and blood platelet (PLT) in peripheral blood of model group were significantly lower than those of normal group (PPγ, C/EBPα, Adiponectin and Leptin in BMMSCs of the model group increased significantly (Pγ, C/EBPα, Adiponectin and Leptin in the middle-dose group diosgenin decreased obviously, which was better than those of Tripterygium glycoside group (P0.05). Conclusion: Diosgenin can promote the recovery of peripheral blood in aplastic anemia mice and improve the hematopoiesis of bone marrow. Diosgenin can reduce the expressions of PPARγ and C/EBPα, the formation of adipocytes and the secretion of Adiponectin and Leptin in adipocytes, and effectively inhibit the process of adipose tissue derived from bone BMMSCs.
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A rapid and sensitive analytical method was developed for the simultaneous determination of fumonisins B1 and B2 in traditional Chinese medicines by HPLC-MS/MS. The detection limits for fumonisins B1 and B2 were 0.25 ng x mL(-1) corresponding to 2 microg x kg(-1) in samples. Recoveries from different samples spiked with fumonisins B1 and B2 at levels ranging from 0.2 to 3 mg x kg(-1) were 84.0%-96.1% and 86.3%-99.3%, respectively. Among the total of 34 samples purchased from local markets, ten samples of which were visibly moldy samples due to inappropriate storage, and 24 were normal samples. The results showed that 6 of the visibly moldy samples and 5 of the normal samples were contaminated with total fumonisins at levels ranging 82.4-2349 microg x kg(-1) and 102-729 microg x kg(-1), respectively.