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Objective To investigate the clinical effect of direct-acting antiviral agent (DAA) in the treatment of chronic hepatitis C (CHC) patients with thrombocytopenia and its effect on platelet count (PLT). Methods A retrospective analysis was performed for 83 CHC patients with thrombocytopenia (PLT 100×10 9 /L at baseline had a greater increase in PLT( P < 0.05). Conclusion CHC patients with thrombocytopenia have significant improvements in liver function and LSM after receiving DAA treatment and obtaining SVR12, and baseline LSM is an independent predictive factor for PLT elevation. There is a significant increase in PLT from baseline to EOT and SVR12.
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ObjectiveTo clarify the medication regularity of WU Zhao-dong,a famous chief physician in traditional Chinese medicine (TCM) of Jiangxi province, and investigate the potential mechanism of potential new prescriptions against chronic renal failure (CRF). MethodThe outpatient prescriptions of WU Zhao-dong from July 2019 to July 2021 were collected. Data mining was carried out by using the Traditional Chinese Medicine Inheritance Auxiliary Platform (V 2.5) to analyze the medication frequency and drug association and obtain potential new prescriptions. The interaction between drug targets in new prescriptions was analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),STRING,and Kyoto Encyclopedia of Genes and Genomes(KEGG), followed by verification by molecular docking and experiments. ResultA total of 200 prescriptions were screened out, with 217 Chinese medicinal drugs involved, and eight new potential prescriptions were derived. To be specific, Prescription 1: Armeniacae Semen Amarum-Astragali Radix-Platycodonis Radix-Angelicae Sinensis Radix-Smilacis Glabrae Rhizoma-fried Atractylodis Macrocephalae Rhizoma, Prescription 2: Saposhnikoviae Radix-Schizonepetae Herba-Kochiae Fructus-Asteris Radix et Rhizoma-Menthae Haplocalycis Herba,Prescription 3:Armeniacae Semen Amarum-Asteris Radix et Rhizoma-Platycodonis Radix-Eriobotryae Folium-prepared Ephedrae Herba, Prescription 4:Perillae Caulis-Codonopsis Radix-Coptidis Rhizoma-Pseudostellariae Radix, Prescription 5:Ecliptae Herba-Astragali Radix Praeparata Cum Melle-Dryopteridis Crassirhizomatis Rhizoma-Rosae Laevigatae Fructus-Coicis Semen-Ligustri Lucidi Fructus, Prescription 6: Lycopi Herba-Lonice Raejaponicae Caulis-Trachelospermi Caulis et Folium-Alismatis Rhizoma, Prescription 7:Scutellariae Radix-Hirudo-Paeoniae Radix Rubra-Eriobotryae Folium-Glehniae Radix, Prescription 8:Glycyrrhizae Radix et Rhizoma-Scrophulariae Radix-Chrysanthemi Indici Flos-Smilacis Glabrae Rhizoma- Serissae Herba. In Prescription 1,18 main chemical components were screened out. Eighty targets of active components of Prescription 1 were predicted, and 37 potential targets for the treatment of CRF were obtained, including interleukin (IL)-6, vascular endothelial growth factor (VEGF), cysteinyl aspartate-specific protease-3 (Caspase-3), nitric oxide synthase 3 (NOS3), and hypoxia-inducible factor-1 (HIF-1). The KEGG pathways involved in the targets of Chinese medicinal drugs and disease mainly included the signaling pathways of lipid and atherosclerosis,NF-κB, Toll-like receptors, and HIF-1. Prescription 1 significantly decreased serum creatinine and urea nitrogen, and increased the content of NO and NOS3 in renal tissues of CRF rats. ConclusionPrescription 1 shows the multi-component and multi-target characteristics of action,and its mechanism may be related to its inhibition of renal fibrosis,anti-inflammation,improvement of intestinal microecology,and improvement of renal hypoxia and ischemia.
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Chronic obstructive pulmonary disease (COPD) is a common and frequently-occurring disease of the respiratory system, characterized by persistent respiratory symptoms and airflow restriction, which is prone to attack repeatedly and affect patients' quality of life seriously. At present, the combination of bronchodilators and inhaled corticosteroids is commonly used in clinic. Although these drugs can alleviate the symptoms of COPD patients, there are certain limitations of the difficulty in controlling the course of the disease effectively and reversing the decline of patients' lung function. Therefore, searching for safer and more effective therapeutic drugs has become a hot research topic nowadays. Traditional Chinese medicine (TCM) has remarkable curative effects and advantages in the prevention and therapy of COPD recently. Based on the increasing research and application of the active components of TCM in the therapy of COPD, studies on their pharmacodynamic mechanism are also more in depth. More and more studies have found that the active components of TCM can treat COPD patients effectively, and the mechanism involved mainly includes the anti-inflammatory, the antioxidant, and the inhibition of apoptosis. By searching and screening the domestic and foreign literatures on the treatment of COPD with the active components of TCM in recent years, the active components of TCM including flavonoids, terpenoids, phenols and saponins have been studied as the research objects, and their effects in improving the pulmonary function and oxidative stress, relieving inflammation and inhibiting apoptosis are expounded. Besides, the mechanism of action, signaling pathways and index molecules have been emphatically summarized, in order to provide the ideas for the clinical therapy and the basic research of COPD.
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OBJECTIVE@#To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+).@*METHODS@#MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot.@*RESULTS@#Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05).@*CONCLUSION@#Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.
Subject(s)
Apoptosis , Benzothiazoles , Cell Line, Tumor , Humans , Leukemia, Myeloid, Acute/genetics , Paclitaxel/therapeutic use , Phenylurea Compounds , RNA, Messenger , STAT5 Transcription Factor/pharmacology , Signal Transduction , fms-Like Tyrosine Kinase 3ABSTRACT
Objective: To observe the changes of serum uric acid levels and clinical characteristic in patients with chronic hepatitis C combined with hyperuricemia after direct antiviral agents (DAA) therapy. Methods: A prospective cohort study was used to investigate the risk of hyperuricemia in patients with chronic hepatitis C who received DAA treatment to obtain sustained virological response. The changes and factors influencing serum uric acid levels after 12 weeks of DAA treatment were observed. Comparisons between groups were performed using χ (2) test or Fisher's exact test, analysis of variance, Student's t test, or the non-parametric Mann-Whitney U test. Serum uric acid (SUA) changes, liver and kidney function indexes before and after treatment were compared by repeated measurement and paired t-test. Uric acid reduction was defined as a decrease in SUA from baseline at 12 weeks after treatment. Rates of change in eGFR, aspartate aminotransferase/platelet ratio, alanine aminotransferase and controlled attenuation parameter were defined from baseline (baseline to 12 weeks after treatment). Binary logistic regression analysis was used to compare the risk factors and factors influencing high and low uric acid level. Results: 161 cases with chronic hepatitis C who received DAA treatment were included, of which 19.3% patients were hyperuricemic. eGFR < 60 ml/(min·1.73 m(2)) and body mass index were independent risk factors for hyperuricemia in patients with chronic hepatitis C (eGFR: OR = 0.123, P = 0.002; body mass index: OR = 1.220, P = 0.002). SUA levels was changed significantly before treatment, at the end of treatment and at 12 weeks after treatment (327.96 vs. 320.76 vs. 314.92, F = 3.272, P = 0.042). At 12 weeks after treatment, SUA, liver stiffness, alanine aminotransferase and control attenuation parameters were all significantly lower than baseline (P < 0.05). The rate of increase in eGFR from baseline and the rate of decrease in controlled attenuation parameter during treatment were the factors influencing SUA reduction (eGFR: OR = 5124, P = 0.000; controlled attenuation index: OR = 0.010, P = 0.039). Conclusion: In chronic hepatitis C, reduced eGFR and body mass index are the risk factors for the development of hyperuricemia and a significant reduction in serum uric acid levels after DAA treatment can eradicate the virus.
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Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Humans , Hyperuricemia/drug therapy , Prospective Studies , Uric AcidABSTRACT
Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.
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Child , Coronary Aneurysm/etiology , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Infliximab/adverse effects , Male , Mucocutaneous Lymph Node Syndrome/drug therapy , Retrospective StudiesABSTRACT
Two cases of epidemic situation of serogroup B meningitis in infants in Shandong Province in 2021 were investigated. Samples of cases and their close contacts were collected for isolation, culture and identification of Neisseria meningitides (Nm). The isolates were subjected to multi-locus sequence typing, outer membrane protein porA and fetA genotyping and drug sensitivity test. Two laboratory-confirmed outbreaks of serogroup B meningitis were reported from Yantai city and Linyi city. The indicated cases were infants aged 5 months and 2 months old respectively. They were not vaccinated with meningitis vaccine. Their epidemiological characteristics and clinical manifestations were similar and the prognosis was good. The same sequence type (ST) of serogroup B Nm strains as the indicated cases was detected in the samples of close family contacts, but without subsequent cases. Among them, Yantai strain was were identified as the type ST-8920, belonging to CC4821 clonal complex, and the genotypes of porA and fetA were p1.21-2, 23 and F3-1. Linyi strain was a new type, belonging to CC4821 clonal complex and the genotypes of porA and fetA were p1.20, 23 and F1-91. The above strains were resistant to penicillin, ciprofloxacin, levofloxacin and Chemitrim, and their sensitivity to cephalosporin decreased. Two cases of infant serogroup B epidemic were relatively rare in China, which were different from the epidemiological and pathogenic characteristics of other Nm serogroups in the past.
Subject(s)
Epidemics , Humans , Infant , Meningitis, Meningococcal/epidemiology , Multilocus Sequence Typing , Neisseria meningitidis , SerogroupABSTRACT
Objective:To explore the value of diffusion tensor imaging (DTI) in evaluating the effects of hyperbaric oxygen therapy (HOT) in treating spinal cord injury.Methods:The modified Allen′s method was used to induce a traumatic spinal cord injury in 30 rats who were then divided randomly into an injured group and a treatment group, each of 15. The treatment group was given HOT twice a day for 3 days, then once a day for a total of 4 weeks. The injured group did not receive HOT. DTI was performed (along with Basso-Beattie-Bresnahan (BBB) evaluation) at 0h, 6h, 24h, as well as 3, 7, 14, 21 and 28 days after the operation. Two-factor repeated measures ANOVA was conducted to analyze any differences in the DTI results: the fractional anisotropy, mean apparent diffusivity, radial diffusivity and axial diffusivity, as well as the BBB scores. LSD t-tests were performed to analyze the significance of the differences at different time points.Results:At each time point after 24h the average FA value of the treatment group was significantly higher than the injured group′s average, while its average MD and RD values were significantly lower. Beyond 14 days the average AD value of the treatment group was significantly higher than that of the injured group. The treatment group′s average BBB score was also significantly higher at all the time points beyond 3 days.Conclusions:DTI results can evaluate spinal cord function and provide valuable information for the dynamic assessment of hyperbaric oxygen therapy after a traumatic spinal cord injury, and the therapy promotes the recovery of motor function, at least in rats.
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Objective:To investigate the incidence, neuroimaging features, and related factors for asymptomatic cerebral small vessel disease(CSVD)in the elderly population.Methods:A total of 201 elderly people with no neurological disease history who had undergone brain magnetic resonance imaging(MRI)examination from October 2019 to August 2020 were enrolled.We calculated the total CSVD score for each participant based on lacunar infarcts(LIs), white matter hyperintensities(WMH), enlarged perivascular spaces(EPVS), and cerebral microbleeds(CMBs)(0-4 points).CSVD neuroimaging features and the correlation between CSVD markers and clinical variables were analyzed.Results:In this study, 133 cases(66.2%)showed MRI features consistent with CSVD.Of whom, LIs were present in 44(21.9%), high-grade PVWMH in 88(43.8%), high-grade DWMH in 30(14.9%), basal ganglia EPVS in 61(30.3%), and CMBs in 92(45.8%).Total CSVD burden score( OR=1.876, 95% CI: 1.045-3.364, χ2=4.441, P=0.035), PVWMH( OR=2.821, 95% CI: 1.517-5.244, χ2=10.752, P=0.001), DWMH( OR=2.130, 95% CI: 1.108-4.092, χ2=5.145, P=0.023), and EPVS( OR=3.258, 95% CI: 1.675-6.334, χ2=12.129, P=0.000)were associated with hypertension.Total CSVD burden score, PVWMH, DWMH, EPVS, and CMB were correlated with increasing age( P<0.05).LIs was positively correlated with PVWMH( b=0.231, P=0.001), DWMH( b=0.247, P=0.000)and EPVS( b=0.215, P=0.001).There was a positive relationship between PVWMH and DWMH( b=0.546, P=0.000)as well as EPVS( b=0.388, P=0.000).DWMH was also positively correlated with EPVS( b=0.357, P=0.000)and CMB( b=0.177, P=0.009). Conclusions:The incidence of asymptomatic CSVD is high in the elderly population.The total CSVD score is a useful measure to evaluate asymptomatic cerebral small vessel disease in the elderly population.Neuroimaging features of asymptomatic CSVD are mainly correlated with age and hypertension.
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Objective:To assess the value of 4-dimensional CT angiography (4D CTA) to predict hemorrhagic transformation (HT) with a new nomogram model in acute ischemic stroke (AIS) patients after endovascular treatment (EVT).Methods:Imaging and clinical data of 101 AIS patients with internal carotid artery and/or middle cerebral artery occlusion who underwent "one-stop" CTA-CT perfusion and EVT in green channel of Beijing Hospital from March 2016 to November 2020 were analyzed retrospectively. The patients were divided into HT group (45 patients) and non-HT group (56 patients). Multivariate logistic regression analysis was used to select relevant clinical and imaging variables, such as age, initial National Institute of Health stroke scale (NIHSS) score, 4D CTA collateral circulation score, Alberta stroke program early CT score (ASPECTS), clot burden score, and a predictive nomogram model were developed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the efficacy of predictive nomogram model for diagnosing HT.Results:Univariate analysis showed that there were significant difference of age[79.00(68.00, 85.00) years, 73.00(62.75, 80.00) years, Z=-2.20, P=0.028], NIHSS score [16.00(12.00, 21.00), 9.50(6.00, 14.00), Z=-4.44, P<0.001], ASPECTS score [5.00(3.00, 8.00), 8.00(7.00, 9.00), Z=-4.23, P<0.001], 4D CTA collateral circulation score [2.00(0, 3.00), 3.00(3.00, 4.00), Z=-5.39, P<0.001], clot burden score [4.00(1.00, 7.00), 7.50(6.00, 9.00), Z=-3.42, P=0.001], location of the occlusion(internal carotid artery/middle cerebral artery occlusion was 23/22, 11/45 cases, χ2=9.70, P=0.002), and atrial fibrillation (27 and 19 cases respectively, χ2=5.83, P=0.016) between HT group and non-HT group. Multivariate logistic regression analysis showed that ASPECTS score (OR=0.64, 95%CI 0.47-0.87), NIHSS score (OR=1.13, 95%CI 1.01-1.26), 4D CTA collateral circulation score (OR=0.40,95%CI 0.22-0.76) were independent predictors of HT in AIS patients ( P<0.05). The AUC of the nomogram based on the ASPECTS score, NIHSS score and 4D CTA collateral circulation score to predict HT of AIS patients was 0.876 (95%CI 0.807-0.945), with a sensitivity of 77.8% and specificity of 87.5%. Conclusions:Patients with low ASPECTS score, high NIHSS score and low 4D CTA collateral circulation score have a higher risk of HT after EVT. The nomogram model may predict the probability of HT of AIS patients and provide effective assistance for clinical decision-making.
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Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.
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Objective:To analyze the expression of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) antigen in hippocampus based on the depression model of juvenile rats caused by chronic unpredictable stress (CUS), and to explore the effect of electroacupuncture vagus nerve on CUS depression model.Methods:Six juvenile SD rats were selected as the control group (without any stimulation), and the rest were divided into CUS group, pseudo stimulation group, fluoxetine group and electroacupuncture group by random number method after CUS modeling, with 6 rats in each group. Fluoxetine group was given 10 mg/kg fluoxetine intervention; control group and CUS group were given the same amount of normal saline intervention; In the electroacupuncture group, the distal vagus nerve was stimulated after ligation, while in the pseudo stimulation group, only vagus nerve was isolated without electrical stimulation. After 28 d of intervention, the five groups were subjected to Open-field Test and Sucrose Preference Test. Hippocampal neurons were detected by hematoxylin and eosin (HE) staining, and the expressions of GFAP and NeuN in hippocampal were detected by immunohistochemistry.Results:After CUS modeling and before intervention, the number of vertical and horizontal movements, sucrose consumption and sucrose preference in CUS group, pseudo stimulation group, fluoxetine group and electroacupuncture group were significantly lower than those in the control group (all P<0.01); After the intervention, the above indexes in CUS group and pseudo stimulation group were still lower than those in the control group (all P<0.01), but the above indexes in fluoxetine group and electroacupuncture group were significantly higher than those in CUS group and pseudo stimulation group (all P<0.01). HE staining showed that the arrangement of hippocampal neurons in CUS group and pseudo stimulation group were loose, and there were cell swelling and pyknosis, which was significantly improved in fluoxetine group and electroacupuncture group. Immunohistochemical results showed that compared with the control group, the expression of GFAP increased and NeuN decreased in the hippocampus of CUS group and pseudo stimulation group (all P<0.01); Compared with CUS group and pseudo stimulation group, the expression of GFAP decreased and NeuN increased in fluoxetine group and electroacupuncture group (all P<0.01). Conclusions:Electroacupuncture of vagus nerve can obviously improve the depression symptoms of juvenile rats, which is similar to fluoxetine, and may be related to regulating the expression of GFAP and Neun in hippocampus.
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Objective To investigate the differences in platelet and platelet parameters between patients with different types and etiologies of acute-on-chronic liver failure (ACLF) and the influence of platelet and its dynamic change on the prognosis of ACLF patients. Methods Clinical data, liver function parameters, platelet, and platelet parameters were collected from 364 patients with ACLF who attended Tianjin Third Central Hospital from January 2014 to December 2018. Platelet level and platelet parameters (platelet distribution width and mean platelet volume) were compared between the patients with different types and etiologies of ACLF, and their influence on the 90-day mortality rate of ACLF patients was analyzed, as well as the association of the dynamic change of platelet at baseline and on days 7 and 14 after admission with the prognosis of patients. The chi-square test was used for comparison of categorical data between groups; the Kruskal-Wallis H test or Mann-Whitney U test was used for comparison of continuous data between groups; the Kaplan-Meier method was used for survival analysis; the univariate and multivariate Cox regression analyses were used to analyze the parameters associated with prognosis; the repeated measures analysis of variance was used to analyze the dynamic change of platelet; receiver operating characteristic (ROC) curve was plotted based on platelet level and overall survival. Results The patients with type C ACLF had a significantly lower platelet level than those with type A/B ACLF (all P < 0.001). Compared with the ACLF patients with hepatitis B, the ACLF patients with autoimmune liver diseases had a significant reduction in mean platelet volume ( P =0.035). Based on the cut-off value obtained by the ROC curve analysis, the patients with a platelet level of < 60.5×10 9 /L had a significantly higher mortality rate than those with a platelet level of ≥60.5×10 9 /L ( P =0.006). Platelet level was an independent protective factor against 90-day death in ACLF patients (hazard ratio=0.995, 95% confidence interval: 0.990-0.999, P =0.026), and the mortality rate increased with the reduction in platelet level. The patients with type C ACLF had a significantly higher mortality rate than those with type A ACLF ( P < 0.05), and the death group tended to have a significantly greater reduction in platelet level ( P < 0.05). Compared with the survival group, the 90-day death group had a significantly greater reduction in platelet ( P =0.032). Conclusion There is a difference in platelet level between ACLF patients with different types. Platelet level is an important indicator for the 90-day prognosis of ACLF patients, and patients with a greater dynamic reduction in platelet tend to have a higher 90-day mortality rate.
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Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of alveolar echinococcosis using high-resolution mass spectrometry with data independent acquisition (DIA), and to identify the key proteins contributing to the pathogenesis of alveolar echinococcosis. Methods Protoscoleces were isolated from Microtus fuscus with alveolar echinococcosis and the experimental model of alveolar echinococcosis was established in female Kunming mice aged 6 to 8 weeks by infection with Echinococcus multilocularis protoscoleces. Mice were divided into the experimental and control groups, and animals in the experimental group was injected with approximately 3 000 protoscoleces, while mice in the control group were injected with the same volume of physiological saline. Mouse liver specimens were sampled from both groups one year post-infection and subjected to pathological examinations. In addition, the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the experimental group and the normal liver specimens (the normal group) were sampled from mice in the control group for DIA proteomics analysis, and the differentially expressed proteins were subjected to bioinformatics analysis. Results A total of 1 020 differentially expressed proteins were identified between the lesion group and the normal group, including 671 up-regulated proteins and 349 down-regulated proteins, and 495 differentially expressed proteins were identified between the peri-lesion group and the normal group, including 327 up-regulated proteins and 168 down-regulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these differentially expressed proteins were involved in peroxisome, peroxisome proliferator-activated receptor (PPAR) and fatty acid degradation pathways, and the peroxisome and PPAR signaling pathways were found to correlate with liver injury. Several differentially expressed proteins that may contribute to the pathogenesis of alveolar echinococcosis were identified in these two pathways, including fatty acid binding protein 1 (Fabp1), Acyl-CoA synthetase long chain family member 1 (Acsl1), Acyl-CoA oxidase 1 (Acox1), Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and Acetyl-Coenzyme A acyltransferase 1B (Acaa1b), which were down-regulated in mice in the experimental group. Conclusion A large number of differentially expressed proteins are identified in the liver of the mouse model of alveolar echinococcosis, and Fabp1, Acsl1, Acox1, Ehhadh and Acaa1b may contribute to the pathogenesis of alveolar echinococcosis.
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Objective To analyze the epidemic characteristics of road traffic injuries in Haishu District of Ningbo City and to provide evidence for effective prevention strategies. Methods Based on the "Ningbo Inpatient Injury Monitoring Report Card", we analyzed the epidemiological characteristics and the influencing factors of hospitalization expenses using the road traffic injuries cases collected from 2015-2019 of Haishu District were analyzed. Results The ratio of male to female was 1.46∶1 among the 8 543 cases. Most cases were between 25 to 64 years old. There were 83.09% cases had junior high school education or below. The top three occupations in the cases were preschoolers, transportation workers, and retired people. Road traffic injuries occurred more frequently in spring for preschoolers and in summer vacation for school-age children. Motor vehicle accidents caused more serious injuries than non-motor vehicle accidents (χ 2=59.069, P<0.001). The economic burden caused by the traffic injuries was heavy. The main influencing factors of hospitalization expenses for road traffic injuries were age, gender, severity of injury and the attribute of injury. The median hospitalization cost was 12 400 Yuan, and the interquartile distance was 23 400 Yuan. Conclusion Road traffic injury not only causes serious bodily injury, but also increases the economic burden of family and society directly or indirectly. Traffic safety education should be carried out for key groups to prevent the occurrence of road traffic injuries.
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OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Subject(s)
Chromosome Aberrations , Humans , In Situ Hybridization, Fluorescence , Multiple Myeloma/genetics , MutationABSTRACT
This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.
Subject(s)
Animals , Glucocorticoids/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Neovascularization, Pathologic/metabolism , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolismABSTRACT
OBJECTIVE To provide reference for safe use of bevacizumab in tumor patient. METHODS Retrospective analysis was performed for a case of tracheomediastinal fistula caused by bevacizumab after radiotherapy in which clinical pharmacist participated. Retrieved from PubMed ,Elsevier Science Direct ,Springer Link ,Wiley Oline Library ,CNKI and Wanfang database ,the cases of respiratory fistula caused by bevacizumab were collected ,and the causes of respiratory fistula were analyzed. RESULTS & CONCLUSIONS Referring to relevant literatures ,combined with the formation position of fistula and considering its correlation with the use time of bevacizumab ,considering that it may be bevacizumab related tracheomediastinal fistula,clinical pharmacists recommended that patients stopped bevacizumab and underwent stent implantation. The patient refused to implant stent for personal reasons ,but the tracheomediastinal fistula improved 3 months after drug withdrawal. Combined with the data of 16 patients with respiratory fistula caused by bevacizumab ,it could be inferred that the use of bevacizumab on the basis of radiotherapy may be the cause of tracheomediastinal fistula ;the mechanism may be related to bevacizumab inhibiting angiogenesis and affecting wound healing. This suggests that for patients who have received radiotherapy ,clinical pharmacists should strengthen medication monitoring and medication education when using bevacizumab ;clinical pharmacists should not only pay attention to the common adverse reactions such as hypertension and bleeding caused by the drug ,but also pay attention to rare but life-threatening adverse reactions such as respiratory fistula ,so as to ensure the safety of drug use.
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Objective@#Viscoelasticity is an essential feature of nerves, although little is known about their viscous properties. The discovery of shear wave dispersion (SWD) imaging has presented a new approach for the non-invasive evaluation of tissue viscosity.The present study investigated the feasibility of using SWD imaging to evaluate diabetic neuropathy using the sciatic nerve in a diabetic rat model. @*Materials and Methods@#This study included 11 diabetic rats in the diabetic group and 12 healthy rats in the control group.Bilateral sciatic nerves were evaluated 3 months after treatment with streptozotocin. We measured the nerve cross-sectional area (CSA), nerve stiffness using shear wave elastography (SWE), and nerve viscosity using SWD imaging. The motor nerve conduction velocity (MNCV) was also measured. These four indicators and the histology of the sciatic nerves were then compared between the two groups. The performance of CSA, SWE, and SWD imaging in distinguishing the two groups was assessed using receiver operating characteristic (ROC) analysis. @*Results@#Nerve CSA, stiffness, and viscosity in the diabetic group was significantly higher than those in the control group (all p < 0.05). The results also revealed a significantly lower MNCV in the diabetic group (p = 0.005). Additionally, the density of myelinated fibers was significantly lower in the diabetic group (p = 0.004). The average thickness of the myelin sheath was also lower in the diabetic group (p = 0.012). The area under the ROC curve for distinguishing the diabetic neuropathy group from the control group was 0.876 for SWD imaging, which was significantly greater than 0.677 for CSA (p = 0.030) and 0.705 for SWE (p = 0.035). @*Conclusion@#Sciatic nerve viscosity measured using SWD imaging was significantly higher in diabetic rats. The viscosity measured using SWD imaging performed well in distinguishing the diabetic neuropathy group from the control group.Therefore, SWD imaging may be a promising method for the evaluation of diabetic neuropathy.
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Objective:To develop and verify a predictive model based on CT characteristics for predicting infected walled-off necrosis (IWON) in MSAP and SAP patients.Methods:The clinical and CT data of 1 322 patients diagnosed as MSAP and SAP according to the 2012 Atlanta revised diagnostic criteria in the First Affiliated Hospital of Naval Medical University from January 2015 to December 2020 were continuously collected. Finally, 126 patients who underwent enhanced CT scans within 3 days after admission and percutaneous catheter drainage of WON during hospitalization were enrolled. Among them, there were 63 MSAP and 63 SAP patients. According to the results of the culture from drainage fluid, the patients were divided into sterile walled-off necrosis group (SWON group, n=31) and infected walled-off necrosis group (IWON group, n=95). Patients were divided into training set (18 patients with SWON and 74 patients with IWON from January 2015 to December 2018) and validation set (13 patients with SWON and 21 patients with IWON from January 2019 to December 2020). Univariate and multivariate logistic regression analysis were performed to establish a model for predicting IWON. The model was visualized as a nomogram. The receiver operating characteristic curve (ROC) was drawn. The predictive efficacy of the model was evaluated by the area under the curve (AUC), sensitivity, specificity and accuracy, and the clinical application value was judged by decision curve analysis (DCA). Results:Univariate regression analysis showed that age, etiology, WON with bubble sign and the lowest CT value of WON were significantly associated with IWON. Multivariate logistic regression analysis showed that older age, biliary acute pancreatitis, WON with bubble sign, and the greater minimum CT value of WON were independent predictors for IWON. The formula for the prediction model was 0.12+ 0.01 age-0.75 hyperlipidemia-1.62 alcoholic-2.62 other causes+ 19.18 WON bubble sign+ 0.10 minimum CT value of WON. The AUC, sensitivity, specificity, and accuracy of the model were 0.85 (95% CI 0.76-0.94), 67.57%, 88.89%, and 71.74% in the training set and 0.78(95% CI0.62-0.94), 66.67%, 84.62%, and 73.53% in the validation set, respectively. The decision analysis curve showed that when the nomogram differentiated IWON from SWON at a rate greater than 0.38, using the nomogram could benefit the patients. Conclusions:The prediction model established based on CT characteristics might non-invasively and accurately predict the presence or absence of IWON in MSAP and SAP patients, and provide a basis for guiding treatment and evaluating prognosis.