Objective To observe the dynamic change of plasma fibrinogen (Fbg) and D-dimer within 48 h in blood samples from the patients with simple severe head injury, and explore the correlation of plasma Fbg and D-dimer levels with the patient's prognosis. Methods In 33 patients with simplese vere head injury, we obtained the blood samples from the artery (A), vein (V) and jugular vein (JV) at different time points (post injury 4, 8, 16, 24, 36 and 48 h) and detected the plasma Fbg and D-dimer levels, respectively. The data were statistically analyzed by SPSS ! 1.5. Results Plasma Fbg was higher than the normal value at 4 h after head injury, and then it was decreased obviously and lower than the normal value at 16 h, and since 24 h it was increased to the normal value. The rising of Fbg was slower in jugular vein than in artery and peripheral vein after 24 h (P<0.05). D-dimer was increased at 4 h after injury, and gradually decreased with the time going on, but the level retained over the normal value until 48 h. In the comparison between the patients with bad prognosis and the ones with satisfactory prognosis, the means of plasma Fbg and D-dimer had significant difference at the same time point (P< 0.05). Conclusions Head injury can result in coagulation disorder, which presents Fbg consumption and decrease and its degradation product D-dimer increase obviously. The changes indicate hypercoagulahale state and secondary hyperfibrinolysis after head trauma. The coagulopathy can be an indicator for judging the severity and prognosis of head injury.

OBJECTIVETo explore the biological and clinical significance of the double mutations of C1673T/C1799G in HBV C promoter (CP).

METHODSTotally 136 patients were enrolled, including 25 asymptomatic carriers (AsC), 38 patients with chronic hepatitis B (CHB), 24 patients with chronic severe hepatitis B (CSHB), 36 cases with liver cirrhosis (LC) and 13 cases with hepatocellular carcinoma (HCC). HBV subgenotypes and mutations in CP of all samples were determined by nested-PCR and direct nucleotide sequence analysis. The C to T mutation at nucleotide 1673 and C to G at nucleotide 1799 were analyzed in different subgenotypes, and the relationships of C1673T/C1799G double mutations with HBV replication, the expression of HBeAg, and with the severity of liver disease after chronic HBV infection were studied.

RESULTSOf the 136 patients, 110 were subgenotype Ba, 1 was Bj, 7 were C1, and 18 were C2. C1673T/C1799G double mutations in Ba were determined in 106 (96. 4%) samples, which was significantly higher than in C1 (14.3%) and C2 (12.5%) subgenotype (P < 0.0001). In contrast to non-mutation group, HBV DNA content in mutation group had no significant difference (P > 0.05). The prevalence of the mutation was lower in HBeAg positive patients (71.4%) than in HBeAg negative patients (87.5%) (P < 0.05). The frequencies of the double mutations were not significantly different among ASC, CHB, CSHB, LC and HCC groups (P > 0.05).

CONCLUSIONIn Ba subgenotype, double mutations of C1673T/C1799G is much popular than in C1 and C2; the mutation has no effect on HBV replication, and may not be associated with the outcome of chronic HBV infection.

Adolescent ; Adult ; Aged ; Female ; Genotype ; Hepatitis B e Antigens ; analysis ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; virology ; Humans ; Male ; Middle Aged ; Mutation ; Promoter Regions, Genetic

Objective To compare the genetic barriers to development of primary mutations related to drug resistance to protease inhibitors (PI), nucleioside reverse transcriptase inhibitors ( NRTI ), and non-nucleioside reverse transcriptase inhibitors ( NNRTI ) among human immunodeficiency virus (HIV)-1 CRF01_AE, CRF07_BC, and CRF08_BC strains, and to understand the difference of varying patterns of drug resistance related mutations within these subtypes. Methods One hundred and ninety naive HIV-positive subjects from Nanning City and Liuzhou City, Guangxi Zhuang Autonomous Region, were recruited. Peripheral blood samples were collected from all participants. HIV-1 RNAs were extracted from plasma, and the pol regions were amplified and sequenced. Sequences were subjected to phylogenetic analysis to determine the subtypes of HIV-1 isolates. Nucleotide transitions and transversions were counted for each primary mutation in these sequences. According to the phenomena that transitions occur on average 2. 5 times frequently than transversions, each transition was scored as 1, and each transversion scored as 2. 5. The sum of the scores for a particular substitution was calculated, and this value was taken as the genetic barrier to development of this mutation. Then, the differences of genetic barriers among the subtypes were assessed by Kruskal-Wallis test and Nemenyi test. Results A total of 123 sequences of CRF01_AE,CRF07_BC and CRF08_BC strains were selected. CRF08_BC had a lower genetic barrier for T/S69Dsubstitution than CRF01_AE and CRF07_BC (χ2 =107. 501, P＜0.01), while CRF01_AE and CRF07_BC had lower genetic barriers for V118I and L210W substitution than CRF08_BC. In addition,CRF07_BC had a decreased genetic barrier for V106M compared with CRF01_AE and CRF08_BC.Conclusions In the presence of the same selective pressure, subtypes CRF01_AE and CRF07_BC may be more likely to develop V118I and L210W substitution than CRF08_BC. However, CRF08_BC may be more likely to develop T/S69D substitution than CRF01_AE and CRF07_BC. Meanwhile, CRF07_BC may be easier to develop V106M substitution than CRF01_AE and CRF08_BC.

AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

Adolescent ; Adult ; Aged ; Body Temperature ; Craniocerebral Trauma ; physiopathology ; therapy ; Female ; Humans ; Hypothermia, Induced ; Male ; Middle Aged ; Treatment Outcome ; Young Adult

OBJECTIVE: To explore the role of cell-surface nucleolin in lipopolysaccharide (LPS)-stimulated expression and secretion of TNF-alpha and IL-1beta in human THP-1 monocytes. METHODS: Immuno-fluorescence assay and Western blot were used to identify the expression of nucleolin on the surface of THP-1 monocytes. Inactivation of nucleolin was induced by anti-nucleolin monoclonal antibody blockage, and the expression and secretion of TNF-alpha and IL-1beta were observed by using reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immuno-sorbent assay (ELISA)respectively in LPS-mediated human THP-1 monocyte inflammatory model. RESULTS: Immuno-fluorescence showed that nucleolin was localized on the cell surface of THP-1 monocytes as indicated by dotted red fluorescence. Western blot assay indicated that nucleolin existed in the cell membrane fractions. RT-PCR assay showed that the expressions of TNF-alpha and IL-1beta mRNA significantly increased at 2 h and 3 h after the treatment with 1000 microg/L LPS. After 1 h pretreatment with anti-nucleolin antibody, the levels of TNF-alpha and IL-1beta mRNA decreased compared with an anti-nucleolin antibody untreated group and an irrelevant IgG+LPS group (P<0.05). ELISA assay showed that the pretreatment with anti-nucleolin antibody inhibited significantly the secretion of LPS-induced levels of TNF-alpha and IL-1beta after 4, 12 and 24 h treatment with 1000 microg/L LPS. CONCLUSION Nucleolin expresses on the cell surface of THP-1 monocytes and involves in the LPS-mediated expression and secretion of TNF-alpha and IL-1beta.
Cell Line ; Cell Membrane ; metabolism ; Humans ; Interleukin-1beta ; biosynthesis ; metabolism ; Lipopolysaccharides ; pharmacology ; Monocytes ; cytology ; metabolism ; Phosphoproteins ; metabolism ; physiology ; RNA-Binding Proteins ; metabolism ; physiology ; Tumor Necrosis Factor-alpha ; biosynthesis ; metabolism

Based on GC-MS and network pharmacology, the active constituents, potential targets, and mechanism of essential oil from Gleditsiae Fructus Abnormalis(EOGFA) against cerebral ischemia/reperfusion(I/R) injury were explored, and the effective constituents were verified by experiment. To be specific, GC-MS was used identify the constituents of the volatile oil. Secondly, the targets of the constituents and disease were predicted by network pharmacology, and the drug-constituent-target network was constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets. Molecular docking was performed to investigate the binding affinity between the active constituents and the targets. Finally, SD rats were used for experimental verification. The I/R injury model was established, and the neurological behavior score, infarct volume, and pathological morphology of brain tissue were measured in each group. The content of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression of vascular endothelial growth factor(VEGF) by Western blot. A total of 22 active constituents and 17 core targets were screened out. The core targets were involved in 56 GO terms and the major KEGG pathways of TNF signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. Molecular docking showed that the active constituents had high affinity to the targets. The results of animal experiment suggested that EOGFA can alleviate the neurological impairment, decrease the cerebral infarct volume and the content of IL-1β, IL-6 and TNF-α, and down-regulate the expression of VEGF. The experiment verified the part results of network pharmacology. This study reflects the multi-component, multi-target, and multi-pathway characteristics of EOGFA. The mechanism of its active constituents is related to TNF and VEGF pathways, which provides a new direction for in-depth research on and secondary development of Gleditsiae Fructus Abnormalis.
Animals ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Oils, Volatile ; Gas Chromatography-Mass Spectrometry ; Interleukin-6 ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A ; Reperfusion Injury ; Cerebral Infarction

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children′s hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

Objective: To assess the prevalence, risk factors and treatment of anemia in patients with chronic kidney disease (CKD). Methods: A descriptive method was used to analyze the prevalence and treatment of anemia in CKD patients based on regional health data in Yinzhou District of Ningbo during 2012-2018. The multivariate logistic regression analysis was used to identify independent influence factors of anemia in the CKD patients. Results: In 52 619 CKD patients, 15 639 suffered from by anemia (29.72%), in whom 5 461 were men (26.41%) and 10 178 were women (31.87%), and anemia prevalence was higher in women than in men, the difference was significant (P<0.001). The prevalence of anemia increased with stage of CKD (24.77% in stage 1 vs. 69.42% in stage 5, trend χ² test P<0.001). Multivariate logistic regression analysis revealed that being women (aOR=1.57, 95%CI: 1.50-1.63), CKD stage (stage 2: aOR=1.10, 95%CI: 1.04-1.16;stage 3: aOR=2.28,95%CI: 2.12-2.44;stage 4: aOR=4.49,95%CI :3.79-5.32;stage 5: aOR=6.31,95%CI: 4.74-8.39), age (18-30 years old: aOR=2.40,95%CI: 2.24-2.57, 61-75 years old: aOR=1.35,95%CI:1.28-1.42, ≥76 years old: aOR=2.37,95%CI:2.20-2.55), BMI (<18.5 kg/m²:aOR=1.29,95%CI: 1.18-1.41;23.0-24.9 kg/m²:aOR=0.79,95%CI: 0.75-0.83;≥25.0 kg/m²:aOR=0.70,95%CI: 0.66-0.74), abdominal obesity (aOR=0.91, 95%CI: 0.86-0.96), chronic obstructive pulmonary disease (aOR=1.15, 95%CI: 1.09-1.22), cancer (aOR=3.03, 95%CI: 2.84-3.23), heart failure (aOR=1.44, 95%CI: 1.35-1.54) and myocardial infarction (aOR=1.54, 95%CI:1.16-2.04) were independent risk factors of anemia in CKD patients. Among stage 3-5 CKD patients with anemia, 12.03% received iron therapy, and 4.78% received treatment with erythropoiesis-stimulating agent (ESA) within 12 months after anemia was diagnosed. Conclusions: The prevalence of anemia in CKD patients was high in Yinzhou. However, the treatment rate of iron therapy and ESA were low. More attention should be paid to the anemia management and treatment in CKD patients.