Search

Human metallothionein-2A (MT2A) protein participates in metal homeostasis, detoxification, oxidative stress reduction, and immune defense. It decreases heavy metal ions and reactive oxygen species (ROS) during injury of cells and tissues. The single nucleotide polymorphisms at the MT2A gene have been associated in various human diseases including cancer. The current study aimed to elucidate associations between MT2A genotypes with the clinical, biochemical, and molecular characteristics that potentially related to lowered MT2A ex-pression. One hundred and forty-one healthy Taiwanese subjects were enrolled from Changhua Show-Chwan Memorial Hospital. Clinical, biochemical and molecular characteristics including the frequent minor allele SNPs, rs28366003 and rs10636, within the MT2A gene were determined. The genotype distribution of MT2A rs10636 fits the Hardy–Weinberg equilibrium. The significant associations with gradually decline of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were identified with MT2A rs10636 and rs28366003 using analysis of variance (ANOVA) with Tukey’s analysis as a post hoc test. We further validated the correlations between the expressions of genes in erythropoiesis, cholesterol synthesis, platelet synthesis, insulin with MT2A using the web-based Gene Expression Profiling Interactive Analysis (GEPIA) databases. The results revealed that hypoxia-inducible factor 1α (HIF-1α), erythropoietin (EPO), lipoprotein lipase (LPL), and lecithin-cholesterol acyltransferase (LCAT) mRNA ex-pression are significantly correlated with MT2A mRNA expression. In conclusion, these results suggested that genetic variations of MT2A rs10636 and rs28366003 might be an important risk factor for erythropoiesis in the Taiwanese general population.

Cadmium (Cd) is a ubiquitous toxic heavy metal in the natural environment that can cause multiple organ damage to the bodies of animals and humans. Selenium yeast (SeY) is a kind of organic selenium (Se) that has a very strong function against Cd-induced injury to tissues or organs. The aim of the current study was to investigate the roles of inflammatory factors and heat shock proteins (HSPs) in inflammatory injury triggered by Cd and to analyze the protective effects of SeY on Cd-induced damnification in the livers of chickens. Two hundred 120-day-old layers were randomly divided into four groups and raised on a conventional diet, or with Se (0.5 mg/kg SeY), Cd (150 mg/kg CdCl2), or Se + Cd (0.5 mg/kg SeY and 150 mg/kg CdCl2) in their basic diets for 120 days. Then, the liver histopathology, production of nitric oxide (NO), activity of inducible NO synthase (iNOS), and mRNA and protein expression levels of inflammatory factors (iNOS, NF-κB, TNF-α, and PTGE) and heat shock proteins (HSPs 27, 40, 60, 70, and 90) were examined. The results showed that exposure to Cd obviously increased Cd accumulation, NO production, iNOS activity, inflammatory factor, and HSP mRNA and protein expression levels and further caused an inflammatory response. Supplementation with SeY had an antagonistic effect on Cd-induced inflammatory injury in chicken livers. Thus, the present study suggests that SeY can be taken as a potential therapeutic for Cd-induced liver inflammatory injury in chickens.

Background The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. Methods We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. Results We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53–69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33–12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06–10.81, p = 0.039). Conclusions A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06970-3.

Background Osteoporotic vertebral fractures are often clinically silent and unrecognized. The present study aimed to determine whether routine chest radiographs could be a potential screening tool for identifying missed vertebral fractures in men aged over 50 years or postmenopausal women, especially those with type 2 diabetes mellitus (T2DM). In this study, we aimed to determine the prevalence of undetected vertebral fractures in elderly Chinese patients with and without T2DM. Methods Clinical data and chest radiographs of 567 individuals with T2DM (T2DM group) and 583 without diabetes (nondiabetic group) at a tertiary hospital in central south China were extracted from the records. Vertebral fractures were specifically looked for on chest radiographs and classified using the Genant semi-quantitative scale. Prevalence was compared between the two groups. Results Mean age and sex composition were comparable between the two groups. Mean weight and body mass index were significantly lower in the T2DM group. In both groups, fractures mostly involved the T11–12 and L1 vertebrae. Moderate/severe fractures were identified in 33.3% individuals in the T2DM group (31.4% men and 36.0% women) versus 23.2% individuals (20.9% men and 25.5% women) in the nondiabetic group. Conclusions Routine chest radiographs could be a useful screening tool for identifying asymptomatic vertebral fractures. Trial registration The study was designed as an observational retrospective study, therefore a trial registration was not necessary.

PURPOSE We aimed to determine the global effects of the Cheneau brace combined with Schroth exercises on adolescent idiopathic scoliosis (AIS). METHODS We analyzed 192 patients with AIS who underwent the Cheneau brace treatment alone or combined with Schroth best practice (SBP) from June 2013 to October 2019. There were 138 patients in the Brace group and 54 patients in the Brace + SBP group. Radiographs were obtained at various treatment durations. Answers to the health-related quality of life (HRQoL) questionnaire were recorded before the intervention and at the time of treatment wean. RESULTS The Cobb angle (-3.55°; p

CD8+ T cell responses play a critical regulatory role in protection against mycoplasma infection-related respiratory diseases. Nanovesicles derived from cell membranes have been shown to induce CD8+ T cell responses. Moreover, the short residence time of mycoplasma membrane-related vaccines in local lymph nodes limits the efficacy of current mycoplasma vaccines. Here, a long-residence pneumonia vaccine is developed using nanovesicles prepared by cell membrane fusion of Mycoplasma hyopneumoniae and interferon-γ (IFN-γ )-primed macrophages, which are grafted with polyethylene glycol to increase residence time in the lymph nodes. Upregulation of intercellular adhesion molecule-1 (ICAM-1) on the membrane of IFN-γ-primed macrophages increases the targeting of the hybrid nanovesicle vaccine to the local lymph nodes, with increased CD8+ T cell activation. A mechanistic study reveals that CD8+ T cell activation is achieved via a pathway involving upregulation of C-C motif chemokine ligand 2/3 expression by E26 transformation-specific sequences, followed by increased immune-stimulatory activity of dendritic cells. In vivo, prophylactic testing reveals that the hybrid nanovesicle vaccine triggers a long-term immune response, as evidenced by a memory CD8+ T cell response against mycoplasma infection. The current study provides a new design strategy for mycoplasma vaccines that involves a hybrid method using biological sources and artificial modification.

Background: Asians with atrial fibrillation carry a higher risk of ischemic stroke than non-Asians even under treatment of nonvitamin K antagonist oral anticoagulants. The purpose of the study was to observe the feasibility of intravenous thrombolytic therapy after administering a reversal agent, idarucizumab, in dabigatran-treated patients with acute ischemic stroke in Taiwan. Methods: Dabigatran-treated patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) after idarucizumab reversal were enrolled in the retrospective nationwide study. The clinical data, treatment course, and outcomes were recorded. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score. Any intracerebral hemorrhage (ICH) after rt-PA was detected by neuroimaging studies. Results: Ten dabigatran-treated patients (6 men, mean age 71.10 ± 7.96 years) with acute ischemic stroke were included. Before stroke, the mean CHA2DS2-VASc score was 4.50 ± 1.57 and 8 patients (80%) received dabigatran 110 mg twice daily. All patients were treated with 5 g idarucizumab, following which the activated partial thromboplastin time normalized. Intravenous rt-PA (mean dose .78 mg/kg) was initiated a mean time of 11.11 minutes after idarucizumab infusion. The NIHSS score improved significantly after thrombolysis (16.0 ± 6.67 at admission to 9.38 ± 4.75 at discharge, P = .016). ICH developed in 3 patients (30%). Two of them were asymptomatic and 1 patient suffered from symptomatic ICH leading to mortality. Conclusion: Our data reconfirmed the feasibility of intravenous rt-PA for Asian stroke patients after reversal of dabigatran effect with idarucizumab.

Purpose The purpose of our study was to determine the risk factors for reduction loss in patients with proximal humeral fractures after locking plate fixation and establish a nomogram prediction model. Methods We retrospectively analyzed the clinical data of proximal humeral fractures patients who had been surgically treated for locking plate in our institution from January 2016 to December 2018. Perioperative information was obtained through the electronic medial record system, univariate and multivariate analyzes were performed to determine the risk factors of reduction loss, and a nomogram model was constructed to predict the risk of reduction loss. The predictive performance and consistency of the model were evaluated by the consistency coefficient (C-index) and the calibration curve, respectively. Results 115 patients were finally enrolled in our study. Multivariate analysis results showed that age, fracture classification, medial comminution, and calcar screw status were independent risk factors for reduction loss. The accuracy of the contour map for predicting transfusion risk was 0.944. Conclusion We found a correlation between reduction loss and age, fracture classification, medial comminution, and calcar screw status after locking plate fixation for proximal humeral fractures patients. Our nomogram is helpful for clinicians to identify high-risk patients, early intervention and reduce the incidence of reduction loss.

Background: C3-Cloud is an integrated care ICT infrastructure offering seamless patient-centered approach to managing multimorbidity, deployed in three European pilot sites. Challenge: The digital delivery of best practice guidelines unified for multimorbidity, customized to local practice, offering the capability to improve patient personalization and benefit. Method: C3-Cloud has adopted a co-production approach to developing unified multimorbidity guidelines, by collating and reconciling best practice guidelines for each condition. Clinical and technical teams at pilot sites and the C3-Cloud consortium worked in tandem to create the specification and technical implementation. Results: C3-Cloud offers CDSS for diabetes, renal failure, depression and congenital heart failure, with over 300 rules and checks that deliver four best practice guidelines in parallel, customized for each pilot site. Conclusions: The process provided a traceable, maintainable and audited digitally delivered collated and reconciled guidelines.

Yan Huang,1 Chun-lan Chen,1 Jing-jing Yuan,1 Hui-min Li,1 Xiao-rong Han,1 Rong-chang Chen,2 Wei-jie Guan,1 Nan-shan Zhong1 1Department of Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute for Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Respiratory Medicine, Shenzhen People’s Hospital, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Wei-jie Guan; Nan-shan ZhongDepartment of Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute for Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, People’s Republic of ChinaTel +86-20-83062876; +86-20-83062719Fax +86-20-83062718; +86-20-83062719Email battery203@163.com; nanshan@vip.163.comBackground: Pseudomonas aeruginosa (PA) colonization confers poor prognosis in bronchiectasis. However, the biomarkers and biological pathways underlying these associations are unclear.Objective: To identify the roles of PA colonization in bronchiectasis by exploring for sputum exosomal microRNA profiles.Methods: We enrolled 98 patients with clinically stable bronchiectasis and 17 healthy subjects. Sputum was split for bacterial culture and exosomal microRNA sequencing, followed by validation with quantitative polymerase chain reaction. Bronchiectasis patients were stratified into PA and non-PA colonization groups based on sputum culture findings. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis to explore biological pathways corresponding to the differentially expressed microRNAs (DEMs) associated with PA colonization.Results: Eighty-two bronchiectasis patients and 9 healthy subjects yielded sufficient sputum that passed quality control. We identified 10 overlap DEMs for the comparison between bronchiectasis patients and healthy subjects, and between PA and non-PA colonization group. Both miR-92b-5p and miR-223-3p could discriminate PA colonization (C-statistic >0.60) and independently correlated with PA colonization in multiple linear regression analysis. The differential expression of miR-92b-5p was validated by quantitative polymerase chain reaction (P

For the first time, we identified 15 cases of Candida auris in Shenyang, China, and then performed a risk factor assessment for these patients compared with 30 control subjects who were hospitalized in the same ward during the same period of time as the infected patients. We found that diarrhea, gastrointestinal decompression, infection, or colonization with other Candida isolates (especially Candida albicans) and tetracycline antibiotics were all risk factors for C. auris infection or colonization. Diarrhea and tetracycline antibiotics were independent risk factors. We suggest clinicians pay special attention to the emergence of multidrug-resistant C. auris infections or colonization.

Wei-Jie Guan,1,2 Jing-Jing Yuan,1 Hui-Min Li,1 Yong-Hua Gao,3 Chun-Lan Chen,1 Yan Huang,1 Rong-Chang Chen,1 Nan-Shan Zhong1,2 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Background: Bronchiectasis is a debilitating disease with chronic airway infection. Proteobacteria, the dominant phylum, can be detected with high-throughput sequencing.Objective: To stratify Proteobacteria compositions according to culture findings in bronchiectasis.Patients and methods: We sampled sputum, split for culture and 16srRNA sequencing, from 106 patients with stable bronchiectasis and 17 healthy subjects. Paired sputa from 22 bronchiectasis patients were collected during exacerbations and convalescence.Results: Forty-five, 41, and 20 patients with clinically stable bronchiectasis had isolated Pseudomonas aeruginosa (PA), other potentially pathogenic microorganisms, and commensals at the initial visit, respectively. The PA group (but not other groups) demonstrated significantly greater relative abundance of Proteobacteria, and lower Shannon–Wiener Diversity Index, Simpson Diversity Index, and richness compared with healthy subjects. Pseudomonas was the dominant genus that discriminated bronchiectasis patients (particularly in the PA group) from healthy subjects. Compared with baseline levels, Proteobacteria community compositions in the PA group, but not in other groups, were more resilient during exacerbations and convalescence.Conclusion: Proteobacteria community compositions could be partially reflected by conventional sputum bacterial culture. Significantly altered Proteobacteria community compositions – particularly, the increased relative abundance of Pseudomonas and diminished community diversity – represent critical targets for novel interventions to restore normal airway microenvironment in patients with bronchiectasis. Keywords: bronchiectasis, Proteobacteria, Pseudomonas aeruginosa, culture, exacerbation

Context Electronegative low-density lipoprotein (LDL) L5 is a naturally occurring, atherogenic entity found at elevated levels in the plasma of patients with metabolic syndrome (MetS) in the absence of elevated plasma LDL levels. Objective To investigate the role of L5 in the mechanism of adipose tissue inflammation associated with MetS. Patients/Setting Plasma LDL isolated from patients with MetS (n = 29) and controls (n = 29) with similar plasma LDL levels was separated into five subfractions, L1 to L5, with increasing electronegativity. Design We examined the invivo effects of L5 on adipose tissue in mice and the in vitro effects of L5 on adipocytokine signaling and monocytes. Results Tail-vein injection of human L5 but not L1 into C57BL/6 mice induced the accumulation of F4/80+ and CD11c+ M1 macrophages. The effects of L5 were attenuated in mice deficient for L5's receptor, lectin-like oxidized LDL receptor 1 (LOX-1). L5 but not L1 induced human adipocytes to release inflammatory adipocytokines. Incubating human THP-1 monocytes with LDL-free culture media from L5-treated adipocytes enhanced the migration of monocytes by 300-fold (P < 0.001 vs L1-treated adipocyte media)-effects that were attenuated by LOX-1 neutralizing antibody. Migrated cells were positive for mature macrophage marker PM-2K, indicating the transformation of monocytes into macrophages. The infiltration of M1 macrophages in adipose tissue was also observed in a previously established hamster model of endogenously elevated L5. Conclusions L5 induces adipose inflammation through LOX-1 by promoting macrophage maturation and infiltration into adipose tissue. Elevated plasma L5 levels may be a novel etiology of adipose tissue inflammation in patients with MetS.

Thyroid function may alter carbohydrate metabolism via influence of insulin, which may in terms of derangement of thyroid function and insulin function result in the development of type 2 diabetes mellitus (T2D). We investigated the association of thyroid disorders with T2D by a cohort study of the Taiwan nationwide health insurance database. A sub-dataset of the National Health Insurance Research Database (NHIRD) was used in this study. The thyroid disease (both hyper- and hypo-thyroidism) group was chosen from patients older than 18 years and newly diagnosed between 2000 and 2012. The control group consisted of randomly selected patients who never been diagnosed with thyroid disease and 4-fold size frequency matched with the thyroid disease group. The event of this cohort was T2D (ICD-9-CM 250.x1, 250.x2). Primary analysis was performed by comparing the thyroid disease group to the control group and the second analysis was performed by comparing the hyperthyroidism subgroup, hypothyroidism subgroup, and control group. The occurrence of T2D in the thyroid disease group was higher than the control group with hazard ratio (HR) of 1.23 [95% confidence interval (CI) = 1.16–1.31]. Both hyperthyroidism and hypothyroidism were significantly higher than control. Significantly higher HR was also seen in female patients, age category of 18 to 39-year-old (y/o) and 40 to 64 y/o subgroups. Higher occurrence of T2D was also seen in thyroid disease patients without comorbidity than in the control group with HR of 1.47 (95% CI = 1.34–1.60). The highest HR was found in the half-year follow-up. There was a relatively high risk of T2D development in patients with thyroid dysfunctions, especially in the period of 0.5 to 1 year after presentation of thyroid dysfunctions. The results suggest performing blood sugar tests in patients with thyroid diseases for early detection and treatment of T2D.

Aim: HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions. This study aimed to develop a new and convenient method for HLA-B*58:01 genotyping and to investigate HLA-B*58:01 distribution in different Chinese populations. Materials & methods: Combining of sequence-specific primers and TaqMan probe, a single-tube duplex real-time PCR assay for HLA-B*58:01 typing was established. Results: The HLA-B*58:01 genotyping result in Buyei (n = 100) by real-time PCR showed 100% concordance with those by sequence-based typing. The prevalence of HLA-B*58:01 carrier in Buyei (17%, n = 100) was significantly higher than those in Northern Han (4%, n = 100), Tibetan (5.1%, n = 99) and Uighur (2%, n = 50) populations (p < 0.05). Conclusion: The newly developed reliable assay was appropriate for HLA-B*58:01 detection prior to allopurinol administration in clinical settings.

The AAA+ ATPase, Thorase, plays a critical role in controlling synaptic plasticity, learning and memory through regulating the expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR). Here, by sequencing a cohort of schizophrenia patients we identify Thorase rare variants (TRV) that cause defects in glutamatergic signaling through impairment in AMPAR internalization, recycling and function. Internalization of AMPAR is significantly reduced in neurons expressing TRVs, leading to increased surface expression of the AMPAR subunit GluA2 and enhanced synaptic transmission. Furthermore, these defects lead to mouse behavioral deficits in schizophrenia-like models and importantly these impairments are rescued by the competitive AMPAR antagonist, perampanel. These findings suggest that Thorase could be an important mediator of symptoms associated with schizophrenia-like behaviors, and support the FDA approved AMPAR antagonist perampanel as a potential treatment strategy for patients with compromised AMPAR-mediated glutamatergic neurotransmission.

Background: Zinc transporters have been considered as essential regulators in many cancers; however, their mechanisms remain unknown, especially in gliomas. Isocitrate dehydrogenase 1(IDH1) mutation is crucial to glioma. This study aimed to investigate whether zinc transporters are correlated with glioma grade and IDH1 mutation status. Materials and Methods: IDH1 mutation status and mRNA expression of four zinc transporters (ZIP4, ZIP9, ZIP11, and ZnT9) were determined by subjecting a panel of 74 glioma tissue samples to quantitative real-time PCR and pyrosequencing. The correlations between the expression levels of these zinc transporter genes and the grade of glioma, as well as IDH1 mutation status, were investigated. Results: Among the four zinc transporter genes, high ZIP4 expression and low ZIP11 expression were significantly associated with higher grade (grades III and IV) tumors compared with lower grade (grades I and II) counterparts (p

Aim: HLA-B*15:02 screening should be performed to prevent antiepileptic drug induced severe cutaneous adverse reactions in populations of Asian origin. This study aimed to develop fast and reliable HLA-B*15:02 genotyping method and to investigate the distribution of HLA-B*15:02 in different Chinese ethnicities. Materials & methods: A single-tube multiplex real-time PCR assay for HLA-B*15:02 genotyping was established by combining allele-specific primers with TaqMan probes. Results: The HLA-B*15:02 genotyping results in Bouyei (n = 100) by the established assay were completely consistent with the corresponding PCR sequence-based typing findings. The percentage of HLA-B*15:02 carrier in Bouyei (19%; n = 100) was significantly higher than those of Han (1%; n = 100), Tibetan (0%; n = 100) and Uyghur (0%; n = 50) populations (p < 0.001). Conclusion: The novel method provides rapid, reliable and cost-effective detection of HLA-B*15:02 allele in clinical applications.

Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures. This consensus statement represents a description of clinical features of AECOPD in the People's Republic of China and a set of recommendations. It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD.

Ethnopharmacological relevance Cornus officinalis (Cornaceae), known in Chinese as “Shanzhuyu,” is a frequently used traditional Chinese medicine. It tastes sour and is astringent and slightly warm in nature. Its fruits have long been used to treat kidney deficiency, high blood pressure, waist and knee pain, dizziness, tinnitus, impotence, spermatorrhea, menorrhagia, and other diseases in China. The main distribution areas are Shanxi and Gansu. Aim of the study This review focused on the ethnopharmacological uses of the herb. We also focus on the phytochemical, pharmacological, and toxicological studies on C. officinalis. The recent analytical methods developed for the quality control of the herb’s constituents are also reviewed. Additionally, future trends and prospects in the study of this herb are proposed. Materials and methods Information on C. officinalis was gathered by searching the internet (PubMed, ScienceDirect, Wiley, ACS, CNKI, Scifinder, Web of Science, Google Scholar, and Baidu Scholar) and libraries. Results This review compiled the ethnopharmacological uses, including the classic prescriptions and historical applications. Approximately 300 chemical compounds have been isolated and identified from C. officinalis. The major active components of the plant are organic acids and iridoids, among which morroniside and loganin have been extensively investigated. The fruit of the plant has been used in treating many diseases in traditional medicine. Scientific studies indicated the herb’s wide range of pharmacological activities, such as hepatic and renal protection, antidiabetes activity, cardioprotection, antioxidation, neuroprotection, antitumor activity, anti-inflammation, analgesic effects, antiaging activity, antiamnesia, antiosteoporosis, and immunoregulation. The analytical methods developed for the quantitative and qualitative determination of various compounds in the herb were further reviewed. Conclusions In this paper, we reviewed various studies conducted on C. officinalis, especially in areas of its ethnopharmacological use, as well as on its phytochemistry, pharmacology, and modern analytical methods used. Some of the herb’s ethnomedical indications have been confirmed by the herb’s pharmacological effects, such as its hepatic and renal protection and the antidiabetic effects. In particular, the crude extract and its chemical composition have exerted good therapeutic effect in diabetic treatment. C. officinalis entails additional attention on its pharmacological effects and drug development to expand its effective use clinically. Many advanced technologies are used for quality testing, but the detection component is exceedingly scarce for synthetically evaluating the quality of C. officinalis herbs. Thus, further research is necessary to investigate the quality control and toxicology of the plant, to further elucidate its clinical use, and to control herbal quality.

We compared midterm prognostic predictors of peripheral artery disease (PAD) with or without diabetes mellitus (DM) presenting with critical lower limb ischemia (CLI). A total of 172 patients with PAD (109 DM; 63 non-DM) were enrolled. The major adverse events (MAEs) were death or amputation. The diabetic group had a higher MAE rate (39% vs 22%, P = .042) with a mean follow-up duration of 30 ± 19 months. In a multivariate binary logistic regression analysis, revascularization (odds ratio = 0.289, P = .006) and higher serum cholesterol (odds ratio=0.988, P = .027) predicted a lower MAE rate in the DM group. In contrast, the presence of severe chronic kidney disease (stage 4 or 5, odds ratio = 5.238, P = .025) was a positive predictor of MAEs in the nondiabetic group. In conclusion, the prognostic predictors of MAE in diabetic and nondiabetic patients with PAD and CLI were different.

Purpose Matrix metalloproteinase 2 (MMP2) has been shown to be expressed in the human sclera, and is increased in the sclera of the eye with myopia induced by form deprivation in chicks when compared with the control eye. The purpose of this study was to examine the relationship between high myopia and MMP2 in a mainland Han Chinese population. Methods Four hundred unrelated patients with high myopia and 400 normal controls in a mainland Han Chinese population were studied. All the subjects were genotyped for 20 tag single nucleotide polymorphisms (SNPs) in MMP2 with the dye terminator-based SNaPshot method. The distribution of the genotypes in the cases and controls was compared with a χ2 test. Screening for mutations in the coding regions and the adjacent intronic regions of MMP2 was performed in 200 patients with high myopia and 200 normal controls by direct sequencing. Results None of the 20 tested SNPs showed significant association with high myopia in this study. Seven variations were detected upon sequencing of the coding regions and the adjacent intronic regions of MMP2 in 200 subjects with high myopia and 200 normal controls. One novel variation, c.1287G>A (p.K429K), was detected in 79 of the 200 patients with high myopia (65 heterozygous and 14 homozygous) and in 84 of the 200 controls (67 heterozygous and 17 homozygous). The c.1810G>A mutation (p. Arg500His) was detected in three of the 200 patients with high myopia but not in the controls. The five other variations, known as polymorphisms, were detected in the case and control groups. Conclusions We found no evidence that MMP2 is responsible for high myopia in these Han Chinese subjects and hence is unlikely to be important in the genetic predisposition to high myopia. Our results imply that MMP2 may not play a major role in high myopia in the Han Chinese population.

Acute intermittent porphyria results from hydroxymethylbilane synthase (HMBS) mutations that markedly decrease HMBS enzymatic activity. This dominant disease is diagnosed when heterozygotes have life-threatening acute attacks, while most heterozygotes remain asymptomatic and undiagnosed. Although400 HMBS mutations have been reported, the prevalence of pathogenic HMBS mutations in genomic/exomic databases, and the actual disease penetrance are unknown. Thus, we interrogated genomic/exomic databases, identified non-synonymous variants (NSVs) and consensus splice-site variants (CSSVs) in various demographic/racial groups, and determined the NSV's pathogenicity by prediction algorithms and in vitro expression assays. Caucasians had the most: 58 NSVs and two CSSVs among ∼92,000 alleles, a 0.00575 combined allele frequency. In silico algorithms predicted 14 out of 58 NSVs as "likely-pathogenic." In vitro expression identified 10 out of 58 NSVs as likely-pathogenic (seven predicted in silico), which together with two CSSVs had a combined allele frequency of 0.00056. Notably, six presumably pathogenic mutations/NSVs in the Human Gene Mutation Database were benign. Compared with the recent prevalence estimate of symptomatic European heterozygotes (∼0.000005), the prevalence of likely-pathogenic HMBS mutations among Caucasians was100 times more frequent. Thus, the estimated penetrance of acute attacks was ∼1% of heterozygotes with likely-pathogenic mutations, highlighting the importance of predisposing/protective genes and environmental modifiers that precipitate/prevent the attacks.

OBJECTIVE. Recently MDCT has become widely used for the evaluation of ischemic heart disease, but clinically the evaluation is primarily focused on the coronary artery only. We describe why and how to comprehensively evaluate the cardiac CT scan, including myocardium, motion, viability, valve, and perfusion aspects related to ischemic heart disease.CONCLUSION. Radiologists should be familiar with the protocol design and comprehensive interpretation of cardiac MDCT to provide comprehensive treatment suggestions for the patients.

Using catheter coronary angiography (CAG) as reference standard, we examined the agreement of 40-detector row computed tomography (MDCT) in triaging patients into the 2 controversial strategies of managing low-risk acute coronary syndrome (ACS).Seventy-eight patients with low-risk ACS received both MDCT and CAG. Early invasive strategy was assigned for the patient if there was significant stenosis (or =50% diameter stenosis) in any of the coronary artery segments with diameter larger than 1.5 mm. The results of MDCT were compared with the CAG for agreement.The overall agreement of the early conservative/early invasive strategy assignment was 92.3%, with kappa value of 0.82 between MDCT and CAG. Only 1 patient needing early invasive strategy was missed by MDCT.Forty-detector row computed tomography is reliable in triaging patients into the 2 strategies of managing low-risk ACS.

The objective of this study was to investigate the possible association of the ABCB1 gene C3435 T polymorphism and the CYP3A5 gene A6986G polymorphism with sirolimus (SRL) trough concentration and dose requirements in Chinese stable renal transplant recipients. Blood samples were collected from 105 healthy volunteers and 50 renal transplant patients, whose polymorphisms of the ABCB1 and CYP3A5 genes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Plasma concentrations of SRL were determined with HPLC. The allele frequencies of the ABCB1 mutation in Chinese healthy volunteers and renal transplant recipients were 51.0% and 44.0% (p0.05), while the allele frequencies of the CYP3A5 mutation were 72.9% and 71.0% (p0.05). The SRL concentration/dose ratio (C/D) in patients with CYP3A5 (*)3/(*)3 were significantly higher than that of those with (*)1 allele (p0.05). However, no significant differences were observed between C/D and ABCB1 SNPs (p0.05). These results confirm that when treated with a SRL-based therapy and low-dose steroids, patients carrying the CYP3A5(*)1 allele required significantly more SRL to achieve adequate blood trough concentrations. In patients with SRL-based therapy, genotyping of the CYP3A5 genes may help to optimize the SRL management in renal transplant recipients.

The present study demonstrates the effect of DHPEA on suppression of irradiation-induced pulmonary fibrosis. A (60)Co irradiator was used to induce pulmonary fibrosis in a rat model at a dose of 22 Gy. The rats of the treatment and positive control group were intraperitoneally injected DHPEA (10 mg/kg) or dexamethasone (DEX; 5 mg/kg) daily for 30 days. Hydroxyproline assay was used to evaluate the fibrosis of pulmonary and lung tissue sections after irradiation. Hematoxylin and eosin (HE) and Masson's trichrome stained lung section were used for alveolitis and fibrosis score analyses, respectively. Immunohistochemistry was used for surfactant protein-B (SPB) and α-SMA expression analysis. Western blot analysis was employed for analysis of nuclear transcription factor NF-E2-related factor 2 (Nrf-2) and its associated antioxidant enzymes like heme oxygenase-1 (HO-1) and NAD (P) H: quinone oxidoreductase-1 (NQO-1). Results revealed a significant decrease in mortality rates and lung index scores, decreased collagen deposition, reduced MDA content and enhanced superoxide dismutase (SOD) activity in DHPEA treated rats compared to DEX-treated rats. DHPEA treatment also inhibited (myo) fibroblast proliferation, and regulated serum levels of TGF-β1, IL-6, IL-10, and TNF-α. In addition, DHPEA-treatment activated Nrf-2 and its downstream antioxidant enzymes HO-1 and NQO-1. Thus DHPEA can be a promising agent for the suppression of irradiation-induced pulmonary fibrosis.

The uptake and metabolism profiles of ginsenoside Rh2 and its aglycon protopanaxadiol (ppd) were studied in the human epithelial Caco-2 cell line. High-performance liquid chromatography-mass spectrometry was applied to determine Rh2 and its aglycon ppd concentration in the cells at different pH, temperature, concentration levels and in the presence or absence of inhibitors. Rh2 uptake was time and concentration dependent, and its uptake rates were reduced by metabolic inhibitors and influenced by low temperature, thus indicating that the absorption process was energy-dependent. Drug uptake was maximal when the extracellular pH was 7.0 for Rh2 and 8.0 for ppd. Rh2 kinetic analysis showed that a non-saturable component (Kd 0.17 nmol x h(-1) x mg(-1) protein) and an active transport system with a Km of 3.95 micromol x l(-1) and a Vmax of 4.78 nmol x h(-1) x mg(-1)protein were responsible for the drug uptake. Kinetic analysis of ppd showed a non-saturable component (Kd 0.78 nmol x h(-1) x mg(-1) protein). It was suggested that active extrusion of P-glycoprotein and drug degradation in the intestine may influence Rh2 bioavailability.

Establishing relationships among brain structures and cognitive functions is a central task in cognitive neuroscience. Existing methods to establish associations among a set of function variables and a set of brain regions, such as dissociation logic and conjunction analysis, are hypothesis-driven. We propose a new data-driven approach to structure-function association analysis. We validated it by analyzing a simulated atrophy study. We applied the proposed method to a study of aging and dementia. We found that the most significant age-related and dementia-related volume reductions were in the hippocampal formation and the supramarginal gyrus, respectively. These findings suggest a multi-component brain-aging model.

Previous studies have reported that estrogen receptors (ERs) are expressed in normal human liver, chronic hepatitis, and benign hepatic tumor tissues. However, decreased expression of ERs can be observed in hepatocellular carcinoma (HCC) and the role of ERs in HCC is not fully understood. Thus, the present study aimed to investigate the molecular mechanism induced by the overexpression of ERα (ERα (ESR1)) in Hep3B cells. We first detected the induction of apoptosis in ER-negative Hep3B cells using DNA fragmentation assay and flow cytometry. We found that ERα and ERα plus 17β-estradiol treatment increased apoptosis in Hep3B cells. Additionally, western blotting showed increased expression of active caspase 3 and tumor necrosis factor α (TNFα (TNF)) inERα-transfected cells. To further understand the importance of SP1-binding sites in theTNFαpromoter, ERα-negative Hep3B cells were co-transfected withERαand a wild-type TNFα plasmid orTNFαwith deleted SP1 regions. Deletion of both distant and primal SP1 sites abolished the activity of ERα, and similar results were observed by blocking the expression of SP1 protein using mithramycin (MA). This result indicates that SP1 protein is essential for ERα-activatedTNFαpromoter activity. Co-immunoprecipitation assay further confirmed the binding interaction between ERα and SP1 in a ligand-dependent manner. In general, we demonstrate that the overexpression of ERα mediates apoptosis in ERα-negative Hep3B cells by the binding of ERα to SP1 protein. Additionally, this ERα–SP1 complex binds to the proximal and distal sites of theTNFαgene promoter and further induces the expression of active caspase 3 in a ligand-dependent manner.

Concomitant renal artery stenosis (RAS) aggravates the presentations and outcomes of coronary artery disease. To date, no reports have been published on the feasibility, safety, and outcomes of concomitant percutaneous renal artery stenting (PTRS) in patients presenting with acute coronary syndrome (ACS) at high clinical risk of RAS.This was a retrospective study. Eighty-two patients who were at high clinical risk of RAS, undergoing simultaneous coronary and renal angiographies between January 2005 and July 2011, were queried from the data of 2186 ACS patients.A total of 80 patients (48 males; age, 77 ± 8 years) were enrolled. Thirty-five patients (43.8%) were found to have significant RAS and all received PTRS. Peripheral arterial disease (PAD) was found to be the only predictive factor for RAS in multivariate analysis. There were no significant differences in the total procedural/fluoroscopic times or the volume of contrast used between RAS/PTRS and non-RAS groups. No extra procedure-related morbidities occurred in the RAS/PTRS group. There were no significant differences in serum creatinine, estimated glomerular filtration rate, or clinical outcomes between the groups at different follow-up points. However, the mean number of antihypertensives decreased significantly 3 months after PTRS. The systolic and diastolic blood pressures also significantly lowered 6 months after PTRS.Significant RAS was not infrequently found in ACS patients at high clinical risk. PAD was the only independent predictive factor. Concomitant PTRS could be safely and effectively performed in the same session as coronary interventions with favorable outcomes.

Compressed sensing (CS) has been used in dynamic cardiac MRI to reduce the data acquisition time. The sparseness of the dynamic image series in the spatial- and temporal-frequency (x-f) domain has been exploited in existing works. In this article, we propose a new k-t iterative support detection (k-t ISD) method to improve the CS reconstruction for dynamic cardiac MRI by incorporating additional information on the support of the dynamic image in x-f space based on the theory of CS with partially known support. The proposed method uses an iterative procedure for alternating between image reconstruction and support detection in x-f space. At each iteration, a truncated ℓ(1) minimization is applied to obtain the reconstructed image in x-f space using the support information from the previous iteration. Subsequently, by thresholding the reconstruction, we update the support information to be used in the next iteration. Experimental results demonstrate that the proposed k-t ISD method improves the reconstruction quality of dynamic cardiac MRI over the basic CS method in which support information is not exploited.

To summarize the cooperative measures on circulation restore during the operation of microvascular submandibular gland transfer.Fifty-six cases of microvascular submandibular gland transfer were performed in Peking University SchoolHospital of Stomatology from January 2005 to March 2009. The related data was collected retrospectively and the cooperative measures on circulation restore during the operation were summarized.The circulation restore of transferred glands were satisfied in all 56 cases when the submandibular gland transfer operation finished. Thrombosis happened in 7 cases within the postoperative 48 hours and the secondary emergency operations were done. At last 6 glands were salvaged and the final successful rate was 98.21%.Successful circulation restore was one of the key points on microvascular submandibular gland transfer. The most important mission of the nursing during the operation was the prevention of vascular crisis. The main measures include persistent wet packing using narceine, fomentation using warm saline and special nursing on postoperative complications. Our experience proves that it is beneficial to the success of operation.

Intramyocardial hematoma is a rare sequela of percutaneous coronary intervention after acute myocardial infarction. Clinical outcomes of intramyocardial hematoma vary from asymptomatic remission to cardiac death. Close follow-up is imperative. Herein, we report the case of a 69-year-old man who had sustained an acute inferior myocardial infarction. During primary percutaneous coronary intervention to the occluded right coronary artery, an intramyocardial hematoma developed and immediately ruptured into the right ventricle. Because the patient remained hemodynamically stable, a conservative approach was taken. Follow-up with serial multidetector computed tomographic imaging elucidated the course and extent of the hematoma and clearly revealed the healing process. After 1 year, this method of imaging showed complete remission of the hematoma. To the best of our knowledge, this is the 1st use of serial multidetector computed tomography to document the remission of an intramyocardial hematoma that ruptured after complicated percutaneous coronary intervention. We believe that multidetector computed tomography is useful in tracing the natural history of intramyocardial hematomas.

Previous observational studies reported that concomitant use of clopidogrel and proton pump inhibitors (PPIs) in patients with prior acute coronary syndrome (ACS) was associated with adverse cardiovascular outcomes. We investigated whether H(2)-receptor antagonist (H(2)RA) is an alternative to PPI in patients with ACS.We conducted a population-based retrospective cohort study of 6552 patients in Taiwan discharged for ACS between 2002 and 2005. Patients were divided into 5 cohorts: clopidogrel plus H(2)RA (n = 252), clopidogrel plus PPI (n = 311), clopidogrel alone (n = 5551), H(2)RA alone (n = 235), and PPI alone (n = 203). The primary outcome was rehospitalization for ACS or all-cause mortality within 3 month of rehospitalization.The 1-year cumulative incidence of the primary outcome was 26.8% (95% CI: 21.5%-33.0%) in the clopidogrel plus H(2)RA cohort and 33.2% (95% CI: 27.8%-39.4%) in the clopidogrel plus PPI cohort, compared with 11.6% (95% CI: 10.8%-12.5%) in the clopidogrel alone cohort (P.0001). No significant difference was observed between the PPI alone cohort (11.0%; 95% CI: 7.1%-16.8%), the H(2)RA alone cohort (11.8%; 95% CI: 8.2%-16.8%), and the clopidogrel alone cohort in terms of the primary outcome. The number needed to harm was 7 with concomitant H(2)RA and 5 with concomitant PPI. On multivariate analysis, concomitant H(2)RA and PPI were independent risk factors predicting adverse outcomes (adjusted hazard ratios, 2.48 and 3.20, respectively; P.0001).Concomitant use of clopidogrel and H(2)RA or PPI after hospital discharge for ACS is associated with increased risk of adverse outcomes.