This study assessed the nutritional status of elderly Chinese lung cancer inpatients using a revised version of the Mini-Nutritional Assessment (MNA®) tool.
Patients and methods:
The revised version of the MNA tool was used to assess the nutritional status of 180 elderly Chinese lung cancer inpatients prior to their scheduled surgery between June 2010 and July 2011. Patients’ demographic data, anthropometric parameters, and biochemical markers were collected and analyzed.
Among the 180 inpatients who underwent the MNA, 9% were malnourished (MNA score < 19), 33% were at risk of malnutrition (MNA score 19–23), and 58% were well nourished (MNA score ≥ 24). There was significant correlation between the MNA scores of patients who were malnourished, at risk of malnutrition, and well nourished (P < 0.001), as well as between total MNA score and most MNA questions. The three patient groups with different nutritional statuses differed significantly in their responses to anthropometrics and global, diet, and subjective assessments.
Incidence rates of malnutrition prior to surgery are high among elderly Chinese lung cancer inpatients. The revised MNA is a valid and reliable tool that can be used to assess and prevent malnutrition among these inpatients.
malnutrition; MNA-SF; nutrition; inpatients; diet
The present study evaluated the efficacy of biphasic human insulin 30 (BHI 30) in type 2 diabetes patients who had failed in therapy with two or more oral antidiabetes drugs (OADs).
This open-label, nonrandomized, 4-month, multicenter, clinical observational study was conducted in Shanghai, China. A total of 660 insulin-naive type 2 diabetes patients with poor glycemic control (glycosylated hemoglobin [HbA1c] ≥7.5%), despite treatment with two or more OADs for more than 6 months, were recruited and received BHI 30 monotherapy or BHI 30 plus OAD(s) (metformin only, α-glucosidase inhibitor only, or both).
Among the 660 subjects, 644 completed the 4-month study. At the end of the study, the median level of HbA1c decreased by 2.0% (from 9.1% to 7.0%) in the BHI 30 monotherapy group and also 2.0% (from 9.5% to 7.3%) in the BHI 30 plus OAD group. More patients achieved the HbA1c <7.0% target in the BHI 30 monotherapy group than in the BHI 30 plus OAD(s) group (47.9% vs. 35.3%, P=0.002). Compared with the expenses of the prior treatment strategy, the median daily cost decreased by 39.8% (4.5 yuan, Chinese RMB) at the end point in the BHI 30 monotherapy group but increased by 20.0% (2.2 yuan) in the BHI 30 plus OAD(s) group (P<0.0001). Moreover, patients in the BHI 30 plus OAD(s) group had fewer minor hypoglycemic episodes than in the BHI 30 monotherapy group (mean of 1.06 vs. 2.77 per patient per year, P<0.0001).
Short-term BHI 30 therapy can improve glycemic control in insulin-naive type 2 diabetes patients after failure of two or more OADs. With higher baseline glucose level, the BHI 30 plus OAD(s) group had lower pharmacoeconomic efficacy than the BHI 30 monotherapy group despite having fewer hypoglycemia events.
Primitive round cell sarcomas of childhood and young adults have been problematic to diagnose and classify. Our goal was to investigate the pathologic and molecular characteristics of small blue round cell tumors (SBRCT) that remained unclassified after exhaustive immunohistochemistry and molecular screening to exclude known sarcoma-related translocations. As rare examples of EWSR1-negative SBRCT have been shown to carry rearrangements for FUS and CIC genes, we undertook a systematic screening for these two genes. CIC rearrangements by FISH were detected in 15/22 (68%), while none showed FUS abnormalities. RACE, RT-PCR and/or long range DNA PCR performed in two cases with frozen material showed that CIC was fused to copies of the DUX4 gene on either 4q35 or 10q26.3. Subsequent FISH analysis confirmed fused signals of CIC with either 4q35 or 10q26.3 region in six cases each. Tumors positive for CIC-DUX4 fusion occurred mainly in male young adult patients (median age: 29 years), with the extremities being the most frequent location. Microscopically, tumors displayed a primitive, round to oval cell morphology with prominent nucleoli, high mitotic count and areas of necrosis. O13 expression was variable, being either diffuse or patchy and tumors mostly lacked other markers of differentiation. Although CIC-DUX4 resulting in a t(4;19) translocation has been previously described in primitive sarcomas, this is the first report implicating the related DUX4 on 10q26 in oncogenesis. These results suggest the possibility of a newly defined subgroup of primitive round cell sarcomas characterized by CIC rearrangements, distinct from Ewing sarcoma family of tumors.
Pollination drop (PD) secretion plays a critical role in wind pollination in many gymnosperms. We conducted detailed investigations on PD secretion in Ginkgo biloba, and found that PDs could not form when the micropyle was removed, but were able to form after removal of the shoot, leaves, ovular stalk, or ovular collar. The duration and volume of the PD increased under high relative humidity, but addition of salt or sugar did not affect PD secretion, its size, or its duration. Morphological and anatomical observations showed that many secretion cells at the nucellus tip contributed to secreting the PD after the formation of pollen chamber. Under laboratory conditions, the PD persisted for approximately 10 d if not pollinated, and re-formed five times after it was removed, with the total volume of PDs reaching approximately 0.4 μL. These results suggested that PDs can be continuously secreted by the tip of the nucellus cells during the pollination stage to increase the chance of capturing pollen from the air. Importantly, PD secretion is an independent behavior of the ovule and PDs were produced apoplastically.
Ginkgo biloba L.; behavior; nucellus cell; ovule; pollination drop; primitive gymnosperm; secretion; wind pollination
Background and Purpose
Recently, we invented a computerized endoscopic balloon manometry (CEBM) to measure variceal pressure (VP) in cirrhotic patient. The purpose of this study was to evaluate the reliability and feasibility of this method, and whether this technique provided further information to pharmacological therapy.
Patients and Methods
VP measurements were performed in 83 cirrhotic patients and compared with HVPG as well as endoscopic bleeding risk parameters. Furthermore, VP was assessed before and during propranolol therapy in 30 patients without previous bleeding.
VP measurements were successful in 96% (83/86) of all patients. Of the 83 patients, the VP correlated closely with the HVPG (P<0.001). The presence of red colour signs and the size of varices were strongly associated with VP. Patients with previous bleeding had higher VP than those who had not yet experienced bleeding. In univariate analysis, the level of VP, the size of varices, and red color signs predicted a higher risk of bleeding. The multiple logistic regression model revealed that VP was the major risk factor for bleeding. In 30 patients receiving propranolol, VP significantly decreased from 21.1±3.5 mmHg before therapy to 18.1±3.3 mmHg after 3 months and to 16.3±4.0 mmHg after 6 months. Comparing the mean decrease in VP with that in hepatic venous pressure gradient (HVPG), the decrease in VP was more obvious than HVPG response to propranolol.
This study showed that CEBM is safe and practical to assess VP in cirrhotic patient. It has the potential to be used as a clinical method to assess the risk of variceal bleeding and the effects of pharmacological therapy.
Effect of vasoactive drugs on esophageal variceal hemodynamics in patients with portal hypertension. Chinese Clinical Trial Registry –TRC-08000252.
Data regarding the patterns and the mechanisms of deregulation of the insulin growth factor (IGF) pathway in adult and pediatric gastrointestinal stromal tumors (GISTs) are limited.
We investigated the expression profiling of the genes encoding the main components of the IGF signaling pathway in 131 GISTs (106 adult, 21 pediatric and 4 young adult) and 25 other soft-tissue sarcomas (STS) using an Affymetrix U133A platform. IGF2 was investigated for loss of imprinting (LOI) whereas IGF1R was analyzed for copy number aberration and mutation.
IGF2 was the most highly overexpressed gene of the IGF pathway in GIST. IGF2 expression was also significantly higher than in other STS. IGF2 expression was correlated to the age onset and mutational status of GIST. Indeed, IGF2 expression was significantly higher in the “adult” group than in the “pediatric” and “young adult” groups. Among adult GIST, IGF2 expression was higher in tumors lacking KIT or PDGFRA mutations in comparison with mutated cases. A trend for a higher expression of IGF2 in resistant GIST in comparison to responsive GIST was also found. Overexpression of IGF2 was not related to LOI. Conversely, the expression of the IGF1R gene was significantly higher in the pediatric group than in the adult group. No copy number gains or mutations of IGF1R were observed.
The IGF pathway is deregulated in GIST with distinct patterns according to age onset and mutational status. The IGF pathway may represent a therapeutic target in patients with primary or secondary resistance to imatinib.
GIST; gastrointestinal stromal tumor; IGF2; IGF1R
Although imatinib mesylate has been a major breakthrough in the treatment of advanced GIST, complete responses are rare and most patients eventually develop resistance to the drug. Thus the possibility of an imatinib-insensitive cell subpopulation within GIST tumors, harboring stem cell characteristics, may be responsible for the clinical failures. However, the existence of a cancer stem cell component in GIST has not been yet established. The present study was aimed to determine whether expression of commonly used stem cell markers in other malignancies, i.e. CD133 and CD44, might identify cells with characteristics of cancer stem/progenitor cells in human GIST. CD133 and CD44 expression in GIST explants was analyzed by flow cytometry, immunofluorescence, and gene expression. Their transcription levels were correlated with clinical and molecular factors in a large, well-annotated cohort of GIST patients. FACS sorted GIST cells based on CD133 and CD44 expression were isolated and used to assess phenotypic characteristics, ability to maintain their surface expression, sensitivity to imatinib, and expression signature. The enrichment in CD133/CD44 cells in the side population (SP) assay was also investigated. CD133 expression was consistently found in GIST. CD133− cells formed more colonies, were more invasive in a matrigel assay, and showed enrichment in the SP cells, compared to CD133+ cells. CD133 expression was also detected in the two imatinib-sensitive GIST cell lines, while was absent in the imatinib-resistant lines. Our results show that CD133 and CD44 are universally expressed in GIST, and may represent a lineage rather than a cancer stem cell marker.
gastrointestinal stromal tumor; CD133; CD44; cancer stem cells; gene expression; KIT
We report the mutational analysis of an artificial oxygen transport protein, HP-7, which operates via a mechanism akin to human neuroglobin and cytoglobin. This protein destabilizes one of two heme-ligating histidine residues by coupling histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Replacement of these glutamate residues with alanine, which is uncharged, increases the affinity of the distal histidine ligand by a factor of thirteen. Paradoxically, it also decreases heme binding affinity by a factor of five in the reduced state and sixty in the oxidized state. Application of a three-state binding model, in which an initial pentacoordinate binding event is followed by a protein conformational change to hexacoordinate, provides insight into the mechanism of this seemingly counterintuitive result: the initial pentacoordinate encounter complex is significantly destabilized by the loss of the glutamate side chains, and the increased affinity for the distal histidine only partially compensates. These results point to the importance of considering each oxidation and conformational state in the design of functional artificial proteins.
Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species.
To evaluate the impacts of the negative lymph nodes (NLNs) count on the prognostic prediction of the ratio of positive and removed lymph nodes (RPL) in cervical cancer patients after radical hysterectomy and pelvic lymphadenectomy (RHPL).
The positive and negative lymph node counts were calculated for 609 postoperative cervical cancer patients. The 5-year survival rate (5-YSR) was examined according to clinicopathologic variables. Cox regression was used to identify independent prognostic factors.
The NLNs count cutoffs were determined to be 10 and 25 with 5-YSR of 62.8% and 80.5%. The RPL of 13 patients who had the NLNs count of 10 or fewer was >20%. Among 242 patients who had 10 < NLNs count ≤ 25, 194 without positive nodes had the 5-YSR of 77.8%, 31 with 0% < RPL ≤ 5% had the 5-YSR of 3.2%, 15 with RPL > 20% had died when follow-up was completed. Among 354 patients who had NLNs count >25, 185 without positive nodes had the 5-YSR of 87.6%, 6 with 0% < RPL ≤ 5% had the 5-YSR of 25%, 15 with 5% < RPL ≤ 20% had the 5-YSR of 4.5%, and 2 with RPL >20% had died when follow-up was completed. Furthermore, stage, histologic grade and RPL were independently correlated with overall survival of cervical cancer patients after RHPL in the multivariate analysis.
RPL was an independent prognostic factor. The NLNs count is a key factor for improvement of survival prediction of RPL in cervical cancer.
Cervical cancer; Lymph node; Pelvic lymphadenectomy; Prognosis
Secondary bacterial infections are a common complication of influenza. Innate immune host defenses appear to be impaired following influenza, leading to susceptibility to subsequent bacterial infections. Alternatively activated macrophages (AAM) in the lungs may play a critical role in eliciting the hypersusceptibility to secondary bacterial pneumonia.
C57BL6 mice were challenged with sublethal doses of the mouse-adapted A/PR/8/34 (PR8) influenza virus or saline and allowed to recover. At complete recovery (day 14), mice were re-challenged with sublethal doses of Streptococcus pneumoniae serotype 3 (Sp3).
PR8-recovered mice developed a rapidly fatal pulmonary infection to a 100-fold sublethal pneumococcal challenge, whereas PR8-naive mice demonstrated no mortality or illness. The cytokines which induce AAM (IL-4 and IL-13) and the expression of genes associated with AAM (Arginase-1, FIZZ1, and YM1) were elevated after PR8 infection. Flow cytometry suggests that alveolar macrophages demonstrate the AAM-phenotype, as indicated by MGL-1 and MHCII expression, in response to PR8 infection. Recovery from PR8 was associated with blunted cytokine responses to TLR ligands.
The mechanisms of immune regulation during recovery from influenza are being elucidated. We provide evidence that pulmonary AAM are induced during influenza infection and may contribute to the elicitation of hypersusceptibility to a secondary bacterial infection.
influenza; secondary pneumonia; alveolar macrophage; alternative activation
The long-range interactions, required to the accurate predictions of tertiary structures of β-sheet-containing proteins, are still difficult to simulate. To remedy this problem and to facilitate β-sheet structure predictions, many efforts have been made by computational methods. However, known efforts on β-sheets mainly focus on interresidue contacts or amino acid partners. In this study, to go one step further, we studied β-sheets on the strand level, in which a statistical analysis was made on the terminal extensions of paired β-strands. In most cases, the two paired β-strands have different lengths, and terminal extensions exist. The terminal extensions are the extended part of the paired strands besides the common paired part. However, we found that the best pairing required a terminal alignment, and β-strands tend to pair to make bigger common parts. As a result, 96.97% of β-strand pairs have a ratio of 25% of the paired common part to the whole length. Also 94.26% and 95.98% of β-strand pairs have a ratio of 40% of the paired common part to the length of the two β-strands, respectively. Interstrand register predictions by searching interacting β-strands from several alternative offsets should comply with this rule to reduce the computational searching space to improve the performances of algorithms.
Peptides show much promise as potent and selective drug candidates. Fusing peptides to a scaffold monoclonal antibody produces a conjugated antibody which has the advantages of peptide activity yet also has the pharmacokinetics determined by the scaffold antibody. However, the conjugated antibody often has poor binding affinity to antigens that may be related to unknown structural changes. The study of the conformational change is difficult by conventional techniques because structural fluctuation under equilibrium results in multiple structures co-existing. Here, we employed our two recently developed electron microscopy (EM) techniques: optimized negative-staining (OpNS) EM and individual-particle electron tomography (IPET). Two-dimensional (2D) image analyses and three-dimensional (3D) maps have shown that the domains of antibodies present an elongated peptide-conjugated conformational change, suggesting that our EM techniques may be novel tools to monitor the structural conformation changes in heterogeneous and dynamic macromolecules, such as drug delivery vehicles after pharmacological synthesis and development.
Existing organic imaging circuits, which offer attractive benefits of light weight, low cost and flexibility, are exclusively based on phototransistor or photodiode arrays. One shortcoming of these photo-sensors is that the light signal should keep invariant throughout the whole pixel-addressing and reading process. As a feasible solution, we synthesized a new charge storage molecule and embedded it into a device, which we call light-charge organic memory (LCOM). In LCOM, the functionalities of photo-sensor and non-volatile memory are integrated. Thanks to the deliberate engineering of electronic structure and self-organization process at the interface, 92% of the stored charges, which are linearly controlled by the quantity of light, retain after 20000 s. The stored charges can also be non-destructively read and erased by a simple voltage program. These results pave the way to large-area, flexible imaging circuits and demonstrate a bright future of small molecular materials in non-volatile memory.
The diagnosis of myoepithelial (ME) tumors outside salivary glands remains challenging, especially in unusual clinical presentations, such as bone or visceral locations. A few reports have indicated EWSR1 gene rearrangement in soft tissue ME tumors, and, in one case each, the fusion partner was identified as either PBX1 or ZNF444. However, larger studies to investigate if these genetic abnormalities are recurrent or restricted to tumors in soft tissue locations are lacking. Sixty-six ME tumors mainly from soft tissue (71%), but also from skin, bone and visceral locations, characterized by classic morphologic features and supporting immunoprofile were studied. Gene rearrangements in EWSR1, FUS, PBX1 and ZNF444 were investigated by FISH. EWSR1 gene rearrangement was detected in 45% of the cases. A EWSR1-POU5F1 fusion was identified in a pediatric soft tissue tumor by 3’RACE and subsequently confirmed in four additional soft tissue tumors in children and young adults. An EWSR1-PBX1 fusion was seen in five cases, while EWSR1-ZNF444 and FUS gene rearrangement was noted in one pulmonary tumor each. In conclusion, EWSR1 gene rearrangement is a common event in ME tumors arising outside salivary glands, irrespective of anatomic location. EWSR1 negative tumors were more often benign, superficially located, and showed ductal differentiation, suggesting the possibility of genetically distinct groups. A subset of soft tissue ME tumors with clear cell morphology harbor an EWSR1-POU5F1 fusion, which can be used as a molecular diagnostic test in difficult cases. These findings do not support a pathogenetic relationship between soft tissue ME tumors and their salivary gland counterparts.
myoepithelial tumor; EWSR1; POU5F1; PBX1; ZNF444
The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.
We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality.
We observed 98 cancer events in the insulin use cohort and 170 in the non-insulin use cohort. Cancer incidence rates were 78.6 and 74.3 per 10,000 patients per year in the insulin users and the non-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P<0.0001) and death from cancer (adjusted RR = 2.16, 95% CI 1.39–3.35, P = 0.001) were all significantly higher in the insulin users than in the non-insulin users.
There was no excess risk of overall cancer in patients with type 2 diabetes who were treated with human insulin. However, a significantly higher risk of liver cancer was found in these patients. Moreover, insulin users showed higher risks of overall and cancer mortality. Considering that individuals treated with insulin were more likely to be advanced diabetic patients, caution should be used in interpreting these results.
It has been a research focus to uncover the genetic determination of complex diseases caused by rare variants. As the vast majority of genomic variants represent background variation, highlighting potentially causal mutations through weighting scheme is critical to the success of rare variants aimed association studies. In this study, we propose a novel Bayesian marker selection approach to perform weighting-based association test. In this approach, individual association signal and its direction are used to weight variants. In addition, the predicted biological function of variants is taken as prior information to direct the selection of likely causal variants. Simulation studies show that the proposed method has improved power over several existing methods in certain conditions. Analyses of two empirical datasets demonstrate its applicability.
weighting; Bayesian marker selection; rare variants; association
Salmonella typhimurium double leu-arg auxotrophs have been shown to be highly effective as antitumor agents in nude mouse models of human metastatic cancer. In order to proceed to clinical development of the S. typhimurium double auxotroph, termed A1-R, it is necessary to evaluate antitumor efficacy in immunocompetent mice. In the present study, we have observed the efficacy of A1-R on the Lewis lung (LLC) carcinoma in vitro as well as in C57BL/6 (C57) immunocompetent mice. In vitro, A1-R treatment of LLC began to induce cell death within one hour. Various doses and schedules of A1-R were administered to C57 mice implanted with LLC, including bolus single intravenous injection; medium dose with weekly intravenous administration and metronomic treatment with small intravenous doses twice a week. Bolus treatment was toxic to the immunocompetent host in contrast to nude mice. Lower-dose weekly doses and metronomic doses were well-tolerated by the immunocompetent host. Weekly intravenous injection with 2 × 107 bacteria and twice a week intravenous injection with 107 bacteria significantly inhibited metastasis formation, while bolus injection was toxic. Intrathoracic administration was performed with 108 A1-R bacteria injected into Lewis lung-bearing C57 mice weekly for three weeks. Lung metastasis was significantly inhibited by intrathoracic bacterial administration without toxicity. The results in this report, demonstrating the anti-metastatic efficacy of S. typhimurium A1-R in immunocompetent mice, indicate the clinical potential of bacterial therapy of cancer.
Salmonella typhimurium; amino acid auxotroph; selective tumor targeting; lung; metastasis; RFP; GFP; fluorescence imaging; confocal microscopy
Like other vascular tumors, epithelioid hemangioendothelioma (EHE) can have multifocal presentation in up to 50% of cases. However, whether multifocal EHE represents an unusual pattern of metastasis or multiple separate primary tumors remains to be elucidated. Our recent identification of WWTR1-CAMTA1 fusion as the genetic hallmark of EHE irrespective of anatomic location was used to clarify this question by comparing the similarity of translocation breakpoints. In our previous study, we found variability of the fusion transcripts of the t(1;3)(p36;q25) translocation among different patients with EHE. Thus, we undertook a molecular analysis of six samples from two patients with multicentric hepatic EHE to test our hypothesis that the presence of identical breakpoints in WWTR1 and CAMTA1 support the monoclonal nature of multifocal EHE. Using RT-PCR and subsequent sequencing we confirmed an identical WWTR1-CAMTA1 fusion transcript product from different nodules in each patient. Our results confirm that multifocal EHE are monoclonal and thus representing metastatic implants of the same neoplastic clone rather than a ‘field-effect’ or synchronous occurrence of multiple neoplastic clones.
vascular tumor; epithelioid hemangioendothelioma; WWTR1-CAMTA1; metastasis; multifocality; monoclonality
Poor survival of mesenchymal stem cells (MSC) compromised the efficacy of stem cell therapy for ischemic diseases. The aim of this study is to investigate the role of PEP-1-CAT transduction in MSC survival and its effect on ischemia-induced angiogenesis.
MSC apoptosis was evaluated by DAPI staining and quantified by Annexin V and PI double staining and Flow Cytometry. Malondialdehyde (MDA) content, lactate dehydrogenase (LDH) release, and Superoxide Dismutase (SOD) activities were simultaneously measured. MSC mitochondrial membrane potential was analyzed with JC-1 staining. MSC survival in rat muscles with gender-mismatched transplantation of the MSC after lower limb ischemia was assessed by detecting SRY expression. MSC apoptosis in ischemic area was determined by TUNEL assay. The effect of PEP-1-CAT-transduced MSC on angiogenesis in vivo was determined in the lower limb ischemia model.
PEP-1-CAT transduction decreased MSC apoptosis rate while down-regulating MDA content and blocking LDH release as compared to the treatment with H2O2 or CAT. However, SOD activity was up-regulated in PEP-1-CAT-transduced cells. Consistent with its effect on MSC apoptosis, PEP-1-CAT restored H2O2-attenuated mitochondrial membrane potential. Mechanistically, PEP-1-CAT blocked H2O2-induced down-regulation of PI3K/Akt activity, an essential signaling pathway regulating MSC apoptosis. In vivo, the viability of MSC implanted into ischemic area in lower limb ischemia rat model was increased by four-fold when transduced with PEP-1-CAT. Importantly, PEP-1-CAT-transduced MSC significantly enhanced ischemia-induced angiogenesis by up-regulating VEGF expression.
PEP-1-CAT-transduction was able to increase MSC viability by regulating PI3K/Akt activity, which stimulated ischemia-induced angiogenesis.
Little information is available regarding the vulnerability of patients with chronic obstructive pulmonary disease (COPD) in China. We aimed to assess this according to patient gender.
A cross-sectional study was conducted in the rural area of Xuzhou in China. We interviewed and administered questionnaires to 2825 male and 2825 female patients with COPD and subjected the data generated to statistical analysis. We compared differences between proportions of male and female patients using the χ2 test.
The rate of current smoking in men was 30.1%, whereas that in women was 10.9%, and 31.5% of men had a history of using biomass fuel compared with 75.3% of women. Further, 26.0% of the male patients and 16.4% of the female patients did not take theophylline regularly when their disease was stable. During acute exacerbations, 65.8% of the male patients and 39.7% of the female patients took theophylline or similar drugs. The average potential shortening of life expectancy was 1.76 years for men and 1.18 years for women. The average indirect economic burden was 11158.4 yuan for men and 7481.2 yuan for women. The quality of life was worse in female patients than in male patients.
We found that patients with COPD were vulnerable and that factors determining vulnerability were different for men than for women. Therefore, we recommend adopting different measures for men and women when attempting to prevent, control, and treat COPD, rehabilitate these patients, and improve their quality of life.
chronic obstructive pulmonary disease; gender; vulnerability
In Vietnam, premature mortality due to AIDS-related conditions is commonly associated with late initiation to antiretroviral therapy (ART). This study explores reasons for late ART initiation among people living with HIV (PLHIV) from the perspectives of health care providers and PLHIV. The study was undertaken in six clinics from five provinces in Vietnam. Baseline CD4 counts were collected from patient records and grouped into three categories: very late initiators (≤100 cells/mm3 CD4), late initiators (100–200 cells/mm3) and timely initiators (200–350 cells/mm3). Thirty in-depth interviews with patients who started ART and 15 focus group discussions with HIV service providers were conducted and thematic analysis of the content performed. Of 934 patients, 62% started ART very late and 11% initiated timely treatment. The proportion of patients for whom a CD4 count was obtained within six months of their HIV diagnosis ranged from 22% to 72%. The proportion of patients referred to ART clinics by voluntary testing and counselling centres ranged from 1% to 35%. Structural barriers to timely ART initiation were poor linkage between HIV testing and HIV care and treatment services, lack of patient confidentiality and a shortage of HIV/AIDS specialists. If Vietnam’s treatment practice is to align with WHO recommendations then the connection between voluntary counselling and testing service and ART clinics must be improved. Expansion and decentralization of HIV/AIDS services to allow implementation at the community level increased task sharing between doctors and nurses to overcome limited human resources, and improved patient confidentiality are likely to increase timely access to HIV treatment services for more patients.
Immunological mechanisms are increasingly recognized in the progression of myelodysplastic syndrome (MDS). Early-stage MDS (E-MDS) is characterized by autoimmune-mediated myelosuppression whereas late-stage MDS (L-MDS) involves immune evasion, giving dysplastic cells growth potential to progress into acute myeloid leukemia. T-helper (Th) 22 is involved in the pathogenesis of inflammatory autoimmunity and tumorigenesis. The roles of Th22 cells in the pathophysiology of E-MDS and L-MDS remain unsettled.
Design and Methods
We studied 37 MDS patients (E-MDS, n = 17; L-MDS, n = 20) and 20 healthy controls to characterize their peripheral blood (PB), as well as 25 MDS patients and 10 healthy controls to characterize their bone marrow(BM). The expression of Interleukin-22 (IL-22), IL-17 or interferon gamma (IFN-γ) was examined in E-MDS, L-MDS patients and controls by flow cytometry. The mRNA expression levels of RAR-related orphan receptor C (RORC), IL-6, tumor necrosis factor alpha (TNF-α) and IL-23 in peripheral blood mononuclear cells (PBMCs) were determined by real-time quantitative polymerase chain reaction. The levels of IL-22 and IL-17 both in PB and BM plasma were examined by enzyme-linked immunosorbent assay.
In E-MDS, peripheral Th17 cells were significantly elevated and correlated with peripheral Th22 cells compared with healthy controls and L-MDS. Significantly higher levels of peripheral Th22 expansion, mRNA expression of IL-6, TNF-α and lower level of RORC mRNA expression were observed in L-MDS compared with E-MDS. No statistical difference was found in IL-23 mRNA expression or plasma IL-22, IL-17 levels among E-MDS, L-MDS and controls.
Our data demonstrated that L-MDS cohort had increased frequencies of peripheral Th22 cells and higher mRNA expression levels of IL-6 and TNF-α, indicating that Th22 cells along with Th17 cells or not are involved in the dynamic immune responses of MDS.
Alexithymia, characterized by difficulties in identifying and describing feelings, is highly indicative of a broad range of psychiatric disorders. Several studies have also discovered the response inhibition ability impairment in alexithymia. However, few studies on alexithymic individuals have specifically examined how emotional context modulates response inhibition procedure. In order to investigate emotion cognition interaction in alexithymia, we analyzed the spatiao-temporal features of such emotional response inhibition by the approaches of event-related potentials and neural source-localization.
The study participants included 15 subjects with high alexithymia scores on the 20-item Toronto Alexithymia Scale (alexithymic group) and 15 matched subjects with low alexithymia scores (control group). Subjects were instructed to perform a modified emotional Go/Nogo task while their continuous electroencephalography activities were synchronously recorded. The task includes 3 categories of emotional contexts (positive, negative and neutral) and 2 letters (“M” and “W”) centered in the screen. Participants were told to complete go and nogo actions based on the letters. We tested the influence of alexithymia in this emotional Go/Nogo task both in behavioral level and related neural activities of N2 and P3 ERP components.
We found that negatively valenced context elicited larger central P3 amplitudes of the Nogo–Go difference wave in the alexithymic group than in the control group. Furthermore, source-localization analyses implicated the anterior cingulate cortex (ACC) as the neural generator of the Nogo-P3.
These findings suggest that difficulties in identifying feelings, particularly in negative emotions, is a major feature of alexithymia, and the ACC plays a critical role in emotion-modulated response inhibition related to alexithymia.
It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo.
Methods and Results
We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis.
CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.