[Analysis on the management of type 2 inflammatory asthma from the guideline of Global Strategy for Asthma Management and Prevention].

Bronchial asthma is a common chronic respiratory disease, which is involved in a variety of cells and cellular components. In 2019, the guidelines for the diagnosis and treatment of asthma issued by the Global Initiative for Asthma (GINA) Committee put forward the concept of type 2 inflammatory asthma for the first time. The updated evolution of GINA guidelines has promoted the development of biological agents and disease treatment, providing effective prevention and treatment for patients with severe asthma and improving disease outcome. This paper expounds the disease mechanism and management suggestions of type 2 inflammatory asthma in GINA guidelines, and analyzes the relevant clinical studies on targeted treatment of type 2 inflammatory asthma in recent years, in order to provide reference for in-depth understanding of level 3 prevention and management of patients with type 2 inflammatory asthma.

[Effect of autologous hematopoietic stem cell transplantation on minimal residual disease in patients with multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on minimal residual disease (MRD) in patients with multiple myeloma (MM). Method: From August 2018 to August 2021, 92 patients newly diagnosed with MM who had received either the bortezomib combined with cyclophosphamide and dexamethasone (VCD) or the bortezomib, lenalidomide and dexamethasone (VRD) induction regimens followed by sequential ASCT were assessed for overall survival (OS) and the MRD negative rate. The differences in efficacy at 100 days after transplantation were assessed according to factors, including age, risk stratification, target organ damage, and pre-transplant regimen, etc. Results: Among the 92 patients, there were 45 males and 47 females, with a median age of 57.3 (35-67) years. Fifty-seven patients received the VCD regimen, and 35 received VRD as induction regimen. Forty-three patients received busulphan combined with cyclophosphamide and etoposide (BCV), and 49 patients received high-dose melphan (HDM) regimen as pre-transplantation treatment. After transplantation, the total complete remission (CR) rate of 92 patients increased from 23.9% (22/92) to 58.7% (54/92), and the MRD negative rate increased from 4.4% (4/92) to 33.7% (31/92), and the differences were statistically significant (all P<0.05). After transplantation, the MRD negative rates of patients with PR, VGPR and ≥CR before transplantation were 17.6% (6/34), 33.3% (12/36) and 59.1% (13/22), respectively (P=0.006). The CR rates of patients with or without plasmacytoma at initial diagnosis were 36.4% (4/11) and 65.4% (53/81), respectively (P=0.029), and the MRD negative rates were 18.2% (2/11) and 39.5% (32/81), respectively (P=0.037), and the differences were statistically significant. The MRD negative rates in high-risk patients and standard-risk group were 30.5% (12/28) and 42.9% (18/59), respectively (P=0.258). For patients who achieved efficacy above VGPR before transplantation, the MRD negative rates after transplantation in VCD-induced group and VRD group were 29% (9/31) and 59.3% (16/27), respectively (P=0.033), and in BCV group and HDM group were 24% (6/25) and 57.6% (19/33), respectively (P=0.016), the differences between the groups were both statistically significant. Conclusion: ASCT can overcome the adverse factors such as high-risk cytogenetic abnormalities, and significantly improve the CR rate and MRD negative rate of MM patients. However, the benefit for patients with plasmacytoma at initial diagnosis is not as good as that of patients without.

[Efficacy comparison and safety analysis of subcutaneous specific immunotherapy with standardized house dust mite allergen in patients with single and multiple allergic rhinitis].

Objective: To investigate the efficacy and safety of house dust mite (HDM) allergen subcutaneous specific immunotherapy (SCIT) in patients with allergic rhinitis (AR) with single dust mite allergy and multiple allergen allergy. Methods: A retrospective study was conducted. A total of 372 patients with allergic rhinitis induced by house dust mite were diagnosed in the allergy clinic of General Hospital of North Theater Command from January 2013 to January 2018.They were treated with house dust mite allergen preparation for standardized SCIT for 3 years or more, and had complete follow-up data. The age ranged from 5 to 55 years, the median age was 13 years, and the average age was (19.4±14.7) years; 216 males and 156 females. According to their age, they were divided into the older group (age >14 years) and younger group (age ≤ 14 years). According to the number of allergens, they were divided into single group (only HDM group allergic to house dust mites) and multi recombination (including 2 or more allergens including house dust mites). The multi recombination was further divided into HDM+1 group, HDM+2 group, HDM+3 group, HDM+4 and above group. Before treatment (T0), 1 year (T1) and 3 years (T2) after SCIT treatment, the patients in each group established files, analyzed and compared the average total nasal symptoms score (TNSS), total non nasal symptoms score (TNNSS), visual analogue scale (VAS), total medicine score (TMS) and rhinoconjunctivitis quality of life questionnaire (RQLQ), and evaluated the clinical efficacy of the treatment and the comparison of various scores in the efficacy of SCIT with different allergens and ages. Record the occurrence of local and systemic adverse reactions of all patients during treatment, and evaluate the safety of SCIT. All scores are measurement data that do not conform to normal distribution. Mann-Whitney U and Kruskai-Wallis test of independent samples are used for inter group comparison, and Bonferroni correction is used for further pairwise comparison; Chi square test and continuity correction method were used for the comparison between count data groups such as the incidence of adverse reactions and the effective rate of TNSS, and a-division method was used for further pairwise comparison. Results: After SCIT treatment, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in T1 and T2 were significantly lower than those in T0, and the scores in T2 were significantly lower than those in T1 (Z=-11.168, -4.786, -6.639, -13.012, -10.652 in T0 vs T1; Z=-13.527, -8.746, -13.397, -14.477, -11.833 in T0 vs T2; Z=-4.721, -4.607, -10.020, -7.180, -5.721 in T1 vs T2; P<0.05). In T1 and T2, compared with the older group, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in younger group were lower, and the differences of various indexes were statistically significant(the median scores of T1: Myounger=3.0, 1.0, 2.0, 4.0, 2.6, Molder=5.0, 2.0, 3.0, 5.0, 3.2; the median scores of T2: Myounger=3.0, 1.0, 0, 2.0, 1.3, Molder=4.0, 1.0, 1.5, 3.0, 2.3; ZT1=-4.525, -5.830, -4.061, -3.608, -2.785; ZT2=-3.847, -4.055, -2.820, -2.998, -3.418; P<0.05). In T1 and T2, the scores of TNSS, VAS and RQLQ in a single group after SCIT treatment were lower than those in multiple recombination(the median scores of T1:Msingle=4.0, 4.0, 2.6, Mmultiple=5.0, 5.0, 3.2; the median scores of T2: Msingle=3.0, 2.0, 1.4, Mmultiple=4.0, 3.0, 2.1), and the difference was statistically significant (ZT1=-3.002, -2.092, -1.977; ZT2=-3.354, -2.469, -2.116; P<0.05). There was no significant difference in TMS (the median score during T1 period: Msingle=2.0, Mmultiple=3.0, ZT1=-1.130; the median score during T2 period: Msingle=1.0, Mmultiple=1.0, ZT2=-1.544; P>0.05). Further comparison within the group showed that there was no significant difference in the improvement rate of TNSS during T2 period among HDM group, HDM+1 group, HDM+2 group and HDM+3 group (HDM vs HDM+1 group χ2=0.277, HDM vs HDM+2 group χ2=0.78, HDM vs HDM+3 group χ2=0.075, HDM+1 vs HDM+2 group χ2=0.057, HDM+1 vs HDM+3 group χ2=0.019, HDM+2 vs HDM+3 group χ2=0.003; P>0.005), the improvement rates were 92.5%, 90.3%, 89.1% and 89.5%. Respectively in HDM group,HDM+1 group, HDM+2 group, HDM+3 group, compared with HDM+4 and above group, the difference was statistically significant (χ2=26.144, 13.254, 15.144, 8.808; P<0.005). The improvement rate of TNSS in HDM+4 and above group was 60.9%. 122 patients had local adverse reactions during the treatment of SCIT, accounting for 32.8%. The local adverse reactions were 759 injections (15 336 injections in total), accounting for 4.95%. Most of them were swelling, dizziness, induration and pruritus at the injection site, which could be relieved by oral antihistamines or within 2 hours. There were 2 cases of local urticaria, once for each case. The symptoms were relieved within 1 week after oral antihistamine. No serious systemic adverse reactions occurred. Conclusion: Standardized SCIT may be a safe and effective treatment for AR patients, and the type of allergen may be one of the important factors affecting the efficacy of SCIT. The efficacy of SCIT was significant in AR patients with three or less allergens other than house dust mite.

[The association between mode of action and adverse outcome pathway and its application in risk assessment].

Risk assessment is a necessary technical means to protect human health and environmental safety. Traditional risk assessment based on toxicity data obtained from animal experiments was difficult to meet the need for risk assessment for a large number of chemicals due to the low throughput, long cycle, high cost and uncertainty of extrapolation to human exposure dose. The proposed risk assessment frameworks, the model of action (MOA) and the adverse outcome pathway (AOP), pointed the way for us to develop new and efficient evaluation methods. In this review, the basic concepts and contents of MOA and AOP, as well as the relationship between them, were introduced. Taking acrylamide (AA) as an example, this review briefly described the application of MOA/AOP framework in chemical risk assessment, so as to provide theoretical guidance for better application of MOA/AOP framework in chemical risk assessment.

[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study].

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) µmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) µmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) µmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study.

BACKGROUND: The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer. METHODS: We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. RESULTS: The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001). CONCLUSIONS: This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

First principles study on 2H-1T' transition in MoS2 with copper.

The electronic properties of MoS2 are strongly controlled by the structure, providing a route to their modulation. We report, based on first principles calculations, that the adsorption of metal atom Cu on the surface can induce the phase transition of MoS2 from the semiconducting 2H to the metallic 1T' phase. Cu adsorption results in effective n-type doping of MoS2 by charge transfer from Cu in the case of the 1T' phase. This is distinct from the behavior in the 2H phase, where Cu does not donate any charge, and it is also distinct from alkali metal adsorption, where charge is donated to both 2H and 1T' MoS2. Charge donation to the 1T' phase by Cu stabilizes it with respect to the 2H structure and importantly, it also reduces the energy barrier between the 2H and 1T' structures. This difference reflects the higher electronegativity of Cu, which also indicates that Cu-modified MoS2 can be expected to be less chemically reactive than MoS2 with alkali metal adatoms. The main atomic mechanism of the structural transition is the gliding of S atoms on the upper surface. Finally, we report the energetics of the 2H to 1T' transition with several other adatoms, Ag, Au, Ni, Pt and Pd, but none of them are as effective as Cu in inducing the transition.

Tetramethylpyrazine (TMPZ) triggers S-phase arrest and mitochondria-dependent apoptosis in lung cancer cells.

Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the traditional Chinese herb Chuanxiong. Several studies have shown its anti-cancer properties. However, its functions in lung cancer and the underlying cellular mechanisms are relatively unknown. Our present study aimed to investigate the effects of TMPZ on A549 and 95D cells. The MTT assay showed that TMPZ decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that TMPZ strongly suppressed colony formation ability in A549 and 95D cells. Flow cytometric analysis revealed that TMPZ induced S phase arrest in lung cancer cells. In addition, TMPZ induced apoptosis, as shown by the results of propidium iodide/Annexin V double-staining. Furthermore, TMPZ decreased mitochondrial membrane potential (∆Ψm) in a dose-dependent manner. Finally, western blot analysis of TMPZ-treated cells revealed the activation of Caspase-3 and the increase of the ratio of Bax/Bcl-2. These results demonstrated that TMPZ could suppress carcinogenesis of lung cancer cells through blocking cell cycle and inducing mitochondria-dependent apoptosis by regulating Caspase-3 and Bax/Bcl-2, suggesting that TMPZ may be a promising drug to treat lung cancer.

[Effects of benzo(a)pyrene on expressions of insulin-degrading enzyme and neprilysin in neuroglia cells].

OBJECTIVE: To investigate effects of benzo(a)pyrene (BaP) on expressions of insulin-degrading enzyme (IDE) and neprilysin (NEP) which have the ability to degrade ß-amyloid (Aß) in neuroglia cells. METHODS: Primary mix-neuroglia cells were cultured from newborn SD rats. After exposure to BaP, Aß1-42 oligomer or Aß1-42 fiber individually or jointly for 24 h, the cell survival rate was measured by cell counting kit-8 (CCK-8). Afterwards, the primary mix-neuroglia cells were divided randomly into six groups: Control group, BaP group (2.00 µmol/L), Aß1-42 oligomer group (20.00 mg/L), BaP plus Aß1-42 oligomer group, Aß1-42 fiber group (20.00 mg/L) and BaP plus Aß1-42 fiber group, of which BaP was pretreated for 12 h followed by cotreatment with different aggregated Aß1-42. The expressions of IDE and NEP were measured by quantitative real-time polymerase chain reaction (qRT-PCR) for mRNA level and Western blotting for protein level. RESULTS: The cell survival rate showed no significant differences after treatment with BaP (≤20.00 µmol/L), Aß1-42 oligomer (20.00, 40.00 mg/L), Aß1-42 fiber (20.00, 40.00 mg/L) or cotreatment with BaP and Aß1-42 oligomer or BaP and Aß1-42 fiber. Compared with the control group, expressions of IDE and NEP in BaP-treated alone group had no obvious change; however, exposure to Aß1-42 oligomer alone significantly increased the mRNA and protein level of IDE (P<0.05), and the BaP pretreatment could significantly inhibit the up-regulated expressions of IDE by Aß1-42 oligomer (P<0.05); on the other hand, exposure either to Aß1-42 fiber alone or under the BaP pretreatment did not change the mRNA and protein level of IDE and NEP obviously. CONCLUSION: On the premise of no significant change of cell survival rate, BaP pretreatment inhibited the up-regulated expressions of IDE in primary mixed neuroglia cells under cotreatment with Aß oligomer, indicating that BaP may disturb degradation of Aß oligomer and cause deposition of ß-amyloid and further induce cognitive decline and acceleration of Alzheimer.

Clinical and immunological analysis of measles patients admitted to a Beijing hospital in 2014 during an outbreak in China.

At the end of 2013, China reported a countrywide outbreak of measles. From January to May 2014, we investigated the clinical and immunological features of the cases of the outbreak admitted to our hospital. In this study, all 112 inpatients with clinically diagnosed measles were recruited from the 302 Military Hospital of China. The virus was isolated from throat swabs from these patients, and cytokine profiles were examined. By detecting the measles virus of 30 of the 112 patients, we found that this measles outbreak was of the H1 genotype, which is the major strain in China. The rates of complications, specifically pneumonia and liver injury, differed significantly in patients aged 18 years: pneumonia was more common in children, while liver injury was more common in adults. Pneumonia was a significant independent risk factor affecting measles duration. Compared to healthy subjects, measles patients had fewer CD4+IL-17+, CD4+IFN-γ +, and CD8+IFN-γ + cells in both the acute and recovery phases. In contrast, measles patients in the acute phase had more CD8+IL-22+ cells than those in recovery or healthy subjects. We recommend that future studies focus on the age-related distribution of pneumonia and liver injury as measles-related complications as well as the association between immunological markers and measles prognosis.

ZNF185 inhibits growth and invasion of lung adenocarcinoma cells through inhibition of the akt/gsk3ß pathway.

Zinc finger (ZNF) proteins, a diverse family of proteins, have multiple biological functions in cancer. Increased expression of ZNF185 has been involved in the regulation of tumor growth and metastasis. However, the function and underlying mechanisms of ZNF185 in the tumorigenesis of lung adenocarcinoma (LAC) remain unclear. The protein expression of ZNF185 was examined in human LAC tissues by immunohistochemical assay. After lentiviral vector-mediated ZNF185 overexpression was infected into the LAC cell lines (A549 and LETPα-2), cell growth and invasive potential were respectively evaluated by MTT and Transwell assays. We found that the protein expression of ZNF185 was significantly downregulated in LAC tissues compared with the adjacent non-cancerous tissues (ANCT) (37.10% vs 58.06%, P=0.015), and was negatively correlated with the lymph node metastasis of the LAC patients (P=0.005). Furthermore, overexpression of ZNF185 reduced cell proliferation and invasion in LAC cells, followed by the downregulation of p-AKT, p-GSK3ß, VEGF and MMP-9 expression. Taken together, our findings indicate that the decreased expression of ZNF185 is linked to the tumor metastasis in human LAC patients, and ZNF185 overexpression inhibits the growth and invasion of LAC cells through inhibition of the AKT/GSK3ß signaling, suggesting that ZNF185 may represent a potential therapeutic target for the treatment of LAC.

Controlling phase transition for single-layer MTe2 (M = Mo and W): modulation of the potential barrier under strain.

Using first-principles DFT calculations, the pathway and the energy barrier of phase transition between 2H and 1T' have been investigated for MoTe2 and WTe2 monolayers. The Phase transition is controlled by the simultaneous movement of metal atoms and Te atoms in their plane without the intermediate phase 1T. The energy barrier (less than 0.9 eV per formula cell) is not so high that the phase transition is dynamically possible. The relative stability of both 2H and 1T' phases and the energy barrier for phase transition can be modulated by the biaxial and uniaxial strain. The dynamic energy barrier is decreased by applying the strain. The phase transition between 2H and 1T' controlled by the strain can be used to modulate the electronic properties of MoTe2 and WTe2.

Protein-protein interaction network construction for cancer using a new L1/2-penalized Net-SVM model.

Identifying biomarker genes and characterizing interaction pathways with high-dimensional and low-sample size microarray data is a major challenge in computational biology. In this field, the construction of protein-protein interaction (PPI) networks using disease-related selected genes has garnered much attention. Support vector machines (SVMs) are commonly used to classify patients, and a number of useful tools such as lasso, elastic net, SCAD, or other regularization methods can be combined with SVM models to select genes that are related to a disease. In the current study, we propose a new Net-SVM model that is different from other SVM models as it is combined with L1/2-norm regularization, which has good performance with high-dimensional and low-sample size microarray data for cancer classification, gene selection, and PPI network construction. Both simulation studies and real data experiments demonstrated that our proposed method outperformed other regularization methods such as lasso, SCAD, and elastic net. In conclusion, our model may help to select fewer but more relevant genes, and can be used to construct simple and informative PPI networks that are highly relevant to cancer.

Clinical characteristics of Clostridium difficile infection in hospitalized patients with antibiotic-associated diarrhea in a university hospital in China.

The purpose of this study was to identify clinical characteristics of Clostridium difficile infection (CDI) in patients with antibiotic-associated diarrhea (AAD). A prospective study was conducted among patients hospitalized in Fudan University Hospital Huashan from August 1, 2012 to July 31, 2013. Toxigenic C. difficile isolates were characterized by PCR ribotyping and multilocus sequence typing. AAD developed in 1.0 % (206/20437) of the antibiotic-treated hospitalized patients and toxigenic C. difficile was isolated from 30.6 % (63/206) of patients with AAD. The frequency of AAD was highest in the intensive care unit (10.7 %); however the proportion of CDI in AAD was highest in the Geriatric Unit (38 %). AAD ranged in severity from mild to moderate. One case with pseudomembranous colitis was identified. Use of carbapenems was found to significantly increase the risk of CDI (OR, 2.31; 95 % CI, 1.22-4.38; p = 0.011). Patient demographics, presumed risk factors, clinical manifestations and laboratory findings revealed no significant difference between patients with CDI and non-C. difficile AAD. Over 90 % of the patients with CDI or non-C. difficile AAD were cured. Two patients had CDI recurrence. Ribotype H was the dominant (18.8 %) genotype, followed by ribotype 012 and ribotype 017. C. difficile plays a significant role in AAD in our setting in China. Because the severity of diarrhea ranges from mild to moderate, it is difficult for Chinese clinicians to identify CDI from AAD patients, therefore CDI should be included in the routine differential diagnoses for hospitalized patients presenting with AAD.

Rapid molecular diagnosis of the Gilbert's syndrome-associated exon 1 mutation within the UGT1A1 gene.

Gilbert's syndrome is suspected in patients with unconjugated hyperbilirubinemia caused by decreased activity of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene in the absence of abnormal liver function and hemolysis. The major genetic variants underlying Gilbert's syndrome are TATA-box repeats of the promoter region and exon 1 G211A of the coding region, particularly in Asians. The efficacy of DNA melting curve analysis, however, has not been established for the G211A mutation. For rapid and accurate molecular diagnosis of Gilbert's syndrome, DNA melting curve analysis was evaluated for its genotyping capability not only for TATA-box repeats of the UGT1A1 promoter, but also for G211A of UGT1A1 exon 1. TA repeats within the TATA-box sequence and the exon 1 G211A mutation of the UGT1A1 gene were analyzed by DNA melting curve analysis. To evaluate the assay reliability, direct sequencing or polyacrylamide gel electrophoresis was used as a comparative method. All homozygous and heterozygous polymorphisms of A(TA)7TAA within the TATA-box allele and of exon 1 G211A mutants of the UGT1A1 gene were successfully identified with DNA melting curve analysis. DNA melting curve analysis is, therefore, an effective molecular method for the rapid diagnosis of Gilbert's syndrome, as it detects not only TATA-box polymorphisms but also the exon 1 G211A mutation located within the UGT1A1 gene.

A health risk assessment of reclaimed municipal wastewater for industrial and miscellaneous use.

The study evaluated the safety of reclaimed water using health risk assessment and biotoxicity tests. The reclaimed water was produced from reverse osmosis and used in industrial and miscellaneous purposes. The health risk assessment was conducted based on the concentrations of detectable pollutants in reclaimed water in a hypothetical scenario. The estimated carcinogenic and non-carcinogenic risks are lower than the generally accepted level. Biotoxicity evaluation included three genotoxicity tests, a chronic toxicity test using medaka fishes, and a subchronic toxicity test using mice. The reclaimed water is not genetically toxic, and does not cause significant chronic effects on these model organisms. These results confirm the safety of using reclaimed water from municipal wastewater treatment plants.

Moderate dynamic compression inhibits pro-catabolic response of cartilage to mechanical injury, tumor necrosis factor-α and interleukin-6, but accentuates degradation above a strain threshold.

OBJECTIVE: Traumatic joint injury can initiate early cartilage degeneration in the presence of elevated inflammatory cytokines (e.g., tumor necrosis factor (TNF)-α and interleukin (IL)-6). The positive/negative effects of post-injury dynamic loading on cartilage degradation and repair in vivo are not well-understood. This study examined the effects of dynamic strain on immature bovine cartilage in vitro challenged with TNF-α + IL-6 and its soluble receptor (sIL-6R) with/without initial mechanical injury. METHODS: Groups of mechanically injured or non-injured explants were cultured in TNF-α + IL-6/sIL-6R for 8 days. Intermittent dynamic compression was applied concurrently at 10%, 20%, or 30% strain amplitude. Outcome measures included sulfated glycosaminoglycan (sGAG) loss (dimethylmethylene blue (DMMB)), aggrecan biosynthesis ((35)S-incorporation), aggrecanase activity (Western blot), chondrocyte viability (fluorescence staining) and apoptosis (nuclear blebbing via light microscopy), and gene expression (qPCR). RESULTS: In bovine explants, cytokine alone and injury-plus-cytokine treatments markedly increased sGAG loss and aggrecanase activity, and induced chondrocyte apoptosis. These effects were abolished by moderate 10% and 20% strains. However, 30% strain amplitude greatly increased apoptosis and had no inhibitory effect on aggrecanase activity. TNF + IL-6/sIL-6R downregulated matrix gene expression and upregulated expression of inflammatory genes, effects that were rescued by moderate dynamic strains but not by 30% strain. CONCLUSIONS: Moderate dynamic compression inhibits the pro-catabolic response of cartilage to mechanical injury and cytokine challenge, but there is a threshold strain amplitude above which loading becomes detrimental to cartilage. Our findings support the concept of appropriate loading for post-injury rehabilitation.

A new automatic algorithm to extract craniofacial measurements from fetal three-dimensional volumes.

OBJECTIVES: Three-dimensional (3D) ultrasound is useful in the prenatal evaluation of fetal craniofacial structures, particularly as it provides a multiplanar view. However, an expert must designate the area of interest and the appropriate view, making measurement of fetal structures using 3D ultrasound both time-consuming and subjective. In this study we propose an image analysis system that measures automatically and precisely the fetal craniofacial structures and evaluate its performance in the second trimester of pregnancy using a new 3D volume analysis algorithm. METHODS: A universal facial surface template model containing the geometric shape information of a fetal craniofacial structure was constructed from a fetal phantom. Using the proposed image analysis system we fitted this stored template model using a model deformation approach to individual fetal 3D facial volumes from 11 mid-trimester fetuses, and extracted automatically the following standard measurements: biparietal diameter (BPD), occipitofrontal diameter (OFD), interorbital diameter (IOD), bilateral orbital diameter (BOD) and distance between vertex and nasion (VN). The same five parameters were measured manually by an expert and the results compared. RESULTS: Comparison of the algorithm-based automatic measurements with manual measurements made by an expert gave correlation coefficients of 0.99 for BPD, 0.98 for OFD, 0.80 for BOD, 0.83 for IOD and 0.99 for VN. There were no significant differences between automatic and manual measurements. CONCLUSION: Our proposed system measures precisely the fetal craniofacial structures using 3D ultrasound, making it potentially useful for clinical service. This system could also be applied to other clinical fields in future testing.

Detection of patients presenting with adverse drug events in the emergency department.

BACKGROUND: Adverse drug events (ADE) have been studied widely in hospitalised and emergency department (ED) patients. Less is known about the ED visits of drug-related injury in Taiwan. This study seeks to determine the incidence, risk and patient outcomes of ADE in an ED population. METHODS: We conducted a prospective observational cohort study of patients 18 years and older presenting to the ED of an urban, tertiary medical centre. ED visits between 1 March 2009 and 28 February 2010 identified by investigators for suspected ADE were further assessed by using the Naranjo Adverse Drug Reaction probability scale. Outcomes (ED disposition, injury severity and preventability) and associated variables (triage, gender, drug category, number of drugs, Charlson comorbidity index score and ADE mechanism) were measured. RESULTS: Of 58,569 ED visits, 452 patients (0.77%) had physician-documented ADE. 24% of patients with ADE were hospitalised with life-threatening conditions, with a mortality rate of 10.0%. The majority of ADE were considered preventable (73.4%), and the unintentional overdose was the most common cause. Cardiovascular agents accounted for the most ADE (25.8%) and consisted of 65.3% of ADE in patients aged 65,years and older. Risk factors for ADE-related hospitalisation were elderly age (odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.4), severity of ADE (OR 6.9, 95% CI 3.3-14.5) and higher Charlson comorbidity index scores (OR 3.4, 95% CI 2.0-5.7). CONCLUSION: ADE-related ED visits are not uncommon in Taiwan and many cases are preventable. ED-based surveillance may provide useful information for monitoring outpatient ADE.

Anomalous wave propagation in a one-dimensional acoustic metamaterial having simultaneously negative mass density and Young's modulus.

A mechanical model representing an acoustic metamaterial that exhibits simultaneously negative mass density and negative Young's modulus was proposed. Wave propagation was studied in the frequency range of double negativity. In view of positive energy flow, it was found that the phase velocity in this range is negative. This phenomenon was also observed using transient wave propagation finite-element analyses of a transient sinusoidal wave and a transient wave packet. In contrast to wave propagation in the region of positive mass and modulus, the peculiar backward wave motion in the region of double negativity was clearly displayed.