Environmental cues regulate epigenetic reprogramming of airway-resident memory CD8+ T cells.

Tissue-resident memory T cells (TRM cells) are critical for cellular immunity to respiratory pathogens and reside in both the airways and the interstitium. In the present study, we found that the airway environment drove transcriptional and epigenetic changes that specifically regulated the cytolytic functions of airway TRM cells and promoted apoptosis due to amino acid starvation and activation of the integrated stress response. Comparison of airway TRM cells and splenic effector-memory T cells transferred into the airways indicated that the environment was necessary to activate these pathways, but did not induce TRM cell lineage reprogramming. Importantly, activation of the integrated stress response was reversed in airway TRM cells placed in a nutrient-rich environment. Our data defined the genetic programs of distinct lung TRM cell populations and show that local environmental cues altered airway TRM cells to limit cytolytic function and promote cell death, which ultimately leads to fewer TRM cells in the lung.

Associations between temporal eating patterns and body composition in young adults: a cross-sectional study.

PURPOSE: The aim of this study was to examine the associations between body composition and temporal eating patterns, including time of first eating occasion, time of last eating occasion, eating window, and eating jet lag (the variability in meal timing between weekdays and weekends). METHODS: A total of 131 participants were included in the study. Temporal eating pattern information was collected through consecutive 7-day eat timing questionnaires and photographic food records. Body composition was assessed by bioelectrical impedance analysis. Multiple linear regression models were used to evaluate the relationships of temporal eating patterns with body composition, and age was adjusted. Eating midpoint was additionally adjusted in the analysis of eating window. RESULTS: On weekdays, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with lower body fat percentage. On weekends, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with higher FFMI. Longer first eating occasion jet lag was associated with lower lean mass. CONCLUSION: Our study suggested that earlier and more regular eating patterns may have a benefit on body composition.

Decomposition analysis on the equity of health examination utilization for the middle-aged and elderly people in China: based on longitudinal CHARLS data from 2011 to 2018.

BACKGROUND: This study aimed to investigate the utilization rate and equity of health examination service among the middle-aged and elderly population in China from 2011 to 2018. The contribution of various determinants to the inequity in health examination service utilization was also examined. METHODS: Data from the China Health and Retirement Longitudinal Survey (CHARLS) were analyzed to assess the health examination service utilization rate among the middle-aged and elderly population. A concentration curve and concentration index were employed to measure the equity of health examination service utilization and decomposed into its determining factors. Horizontal inequity index was applied to evaluate the trends in equity of health examination service. RESULTS: The health examination service utilization rates among the middle-aged and elderly population were 29.45%, 20.69%, 25.40%, and 32.05% in 2011, 2013, 2015, and 2018, respectively. The concentration indexes for health examination service utilization were 0.0080 (95% CI: - 0.0084, 0.0244), 0.0155 (95% CI: - 0.0054, 0.0363), 0.0095 (95% CI: - 0.0088, 0.0277), and - 0.0100 (95% CI: - 0.0254, 0.0054) from 2011 to 2018, respectively. The horizontal inequity index was positive from 2011 to 2018, evidencing a pro-rich inequity trend. Age, residence, education, region, and economic status were the major identified contributors influencing the equity of health examination service utilization. CONCLUSIONS: A pro-rich inequity existed in health examination service utilization among the middle-aged and elderly population in China. Reducing the wealth and regional gap, providing equal educational opportunities, and strengthening the capacity for chronic disease prevention and control are crucial for reducing the inequity in health examination service utilization.

T Cell Receptor Diversity and Lineage Relationship between Virus-Specific CD8 T Cell Subsets during Chronic Lymphocytic Choriomeningitis Virus Infection.

Recent studies on chronic viral infections have defined a novel programmed cell death 1-positive (PD-1+) T cell factor 1-positive (TCF1+) stem-like CD8 T cell subset that gives rise to the terminally differentiated exhausted CD8 T cells. In this study, we performed T cell receptor beta (TCRß) sequencing of virus-specific CD8 T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection to examine the TCR diversity and lineage relationship of these two functionally distinct subsets. We found that >95% of the TCR repertoire of the exhausted CD8 T cell subset was shared with the stem-like CD8 T cells. The TCR repertoires of both CD8 T cell subsets were composed mostly of a few dominant clonotypes, but there was slightly more breadth and diversity in the stem-like CD8 T cells than their exhausted counterpart (∼40 versus ∼15 GP33+ clonotypes; ∼20 versus ∼7 GP276+ clonotypes). Interestingly, the breadth of the TCR repertoire was broader during the early stages (day 8) of the chronic infection than the later stages (days 45 to 60), showing that there was a narrowing of the TCR repertoire during chronic infection (∼2-fold GP33+ and GP276+ stem-like subset; ∼10-fold GP33+ and ∼5-fold GP276+ exhausted subset). In contrast, during acute LCMV infection, the TCR repertoire was much broader in both GP33-specific effector (∼160 clonotypes) and memory CD8 T cells (∼160 clonotypes). Overall, our data demonstrate that the virus-specific CD8 T cell TCR repertoire is broad and remains stable after acute LCMV infection, but it contracts and is narrower during chronic infection. Our study also shows that the repertoire of the exhausted CD8 T cell subset is almost completely derived from the stem-like CD8 T cell subset during established chronic LCMV infection.IMPORTANCE CD8 TCR repertoires responding to chronic viral infections (HIV, hepatitis C virus [HCV], Epstein-Barr virus [EBV], and cytomegalovirus [CMV]) have limited breadth and diversity. How these repertoires change and are maintained throughout the chronic infection are unknown. We thus characterized the LCMV-specific CD8 TCR repertoires of stem-like and terminally exhausted subsets generated during chronic LCMV infections. During chronic LCMV infections, the repertoires started as diverse but became more clonal at the late time point. Further, the exhausted subset was composed of dominant clonotypes that were shared with the stem-like subset. Together, we demonstrate that the TCR repertoire contracts over time and is almost exclusively derived from the stem-like subset late during the persistent viral infection. Our data suggest that dominant clonotypes in the exhausted subset are derived from a diverse pool of stem-like clonotypes, which may be contributing to the clonality observed during chronic viral infections.

[A Cross-sectional Study of Osteoporosis and Cardiovascular Calcification in Patients with Chronic Kidney Disease at Different CKD Stages].

OBJECTIVE: To investigate the status of osteoporosis and cardiovascular calcification in patients with chronic kidney disease (CKD) with different stages, and analyze the correlation between the stages and markers of bone metabolism To correlation. METHODS: A total of 368 CKD patients at stage 3-5 who were treated in First Affiliated Hospital Affiliate to Chongqing Medical University and Chongqing Fuling Central Hospital from July 2017 to January 2018 were enrolled. A total of 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Age, gender and body mass index (BMI) of all study objects at enrollment time were collected. The levels of estimate glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), albumin (ALB), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), procollagen Ⅰ N-terminal peptide (PINP) and ß-crosslaps (ß-CTX) were detected. The occurrence of osteoporosis, vascular calcification and heart valve calcification was detected. Pearson correlation analysis was applied to analyze correlation between eGFR, serum bone metabolism markers and osteoporosis, cardiovascular calcification. RESULTS: Compared with control group, levels of serum P, iPTH, BALP, PINP and ß-CTX were significantly increased in CKD stage 3-5 group ( P<0.05), while levels of eGFR and serum Ca were decreased ( P<0.05). With the increase of CKD staging, changes of their levels were more significant ( P<0.05). The incidence of vascular calcification and heart valve calcification in CKD stage 5 hemodialysis group was higher than that in CKD stage 3-4 group and CKD stage 5 without dialysis group ( P<0.05). eGFR was positively correlated with serum Ca in CKD patients at stage 3-5 ( P<0.05), while negatively correlated with serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). The occurrence of osteoporosis, vascular calcification and heart valve calcification was negatively correlated with increase of eGFR and serum Ca levels in CKD patients at stage 3-5 ( P<0.05), while positively correlated with increase of levels of serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). CONCLUSION: The levels of serum bone metabolism markers and eGFR are closely related to occurrence of osteoporosis and cardiovascular calcification in CKD patients at stage 3-5.

Why Are CD8 T Cell Epitopes of Human Influenza A Virus Conserved?

The high degree of conservation of CD8 T cell epitopes of influenza A virus (IAV) may allow for the development of T cell-inducing vaccines that provide protection across different strains and subtypes. This conservation is not fully explained by functional constraint, since an additional mutation(s) can compensate for the replicative fitness loss of IAV escape variants. Here, we propose three additional mechanisms that contribute to the conservation of CD8 T cell epitopes of IAV. First, influenza-specific CD8 T cells may protect predominantly against severe pathology rather than infection and may have only a modest effect on transmission. Second, polymorphism of the human major histocompatibility complex class I (MHC-I) gene restricts the advantage of an escape variant to only a small fraction of the human population who carry the relevant MHC-I alleles. Finally, infection with CD8 T cell escape variants may result in a compensatory increase in the responses to other epitopes of IAV. We use a combination of population genetics and epidemiological models to examine how the interplay between these mechanisms affects the rate of invasion of IAV escape variants. We conclude that for a wide range of biologically reasonable parameters, the invasion of an escape variant virus will be slow, with a timescale of a decade or more. The results suggest T cell-inducing vaccines do not engender the rapid evolution of IAV. Finally, we identify key parameters whose measurement will allow for more accurate quantification of the long-term effectiveness and impact of universal T cell-inducing influenza vaccines.IMPORTANCE Universal influenza vaccines against the conserved epitopes of influenza A virus have been proposed to minimize the burden of seasonal outbreaks and prepare for the pandemics. However, it is not clear how rapidly T cell-inducing vaccines will select for viruses that escape these T cell responses. Our mathematical models explore the factors that contribute to the conservation of CD8 T cell epitopes and how rapidly the virus will evolve in response to T cell-inducing vaccines. We identify the key biological parameters to be measured and questions that need to be addressed in future studies.

IL-36γ Protects against Severe Influenza Infection by Promoting Lung Alveolar Macrophage Survival and Limiting Viral Replication.

Although influenza virus infection remains a concerning disease for public health, the roles of individual cytokines during the immune response to influenza infection are not fully understood. We have identified IL-36γ as a key mediator of immune protection during both high- and low-pathogenesis influenza infection. Il36g mRNA is upregulated in the lung following influenza infection, and mice lacking IL-36γ have greatly increased morbidity and mortality upon infection with either H1N1 or H3N2 influenza. The increased severity of influenza infection in IL-36γ-knockout (KO) mice is associated with increased viral titers, higher levels of proinflammatory cytokines early in infection, and more diffuse pathologic conditions late in the disease course. Interestingly, the increased severity of disease in IL-36γ-KO mice correlates with a rapid loss of alveolar macrophages following infection. We find that the alveolar macrophages from naive IL-36γ-KO mice have higher expression of M2-like surface markers compared with wild-type (WT) mice and show increased apoptosis within 24 h of infection. Finally, transfer of WT alveolar macrophages to IL-36γ-KO mice restores protection against lethal influenza challenge to levels observed in WT mice. Together, these data identify a critical role for IL-36γ in immunity against influenza virus and demonstrate the importance of IL-36γ signaling for alveolar macrophage survival during infection.

WeChat as a Platform for Problem-Based Learning in a Dental Practical Clerkship: Feasibility Study.

BACKGROUND: Problem-Based-Learning (PBL) has been widely accepted in student-centered medical education. Since WeChat is the most popular communication app in China, we have chosen to use WeChat as new platform for online PBL in order to reduce the limitations of traditional PBL in dental practical clerkships. OBJECTIVE: This study aims to demonstrate the feasibility and acceptability of online PBL using WeChat (WeChat-PBL) in a dental practical clerkship. METHODS: A total of 72 students in a dental practical clerkship and 10 tutors participated in this study from June to August 2017. We created 10 WeChat groups to provide a communication platform for the PBL teaching, in which the students selected the PBL cases themselves from their practical clerkship. After each individual PBL case, group members were required to complete an evaluation on the PBL process itself. A final questionnaire survey was completed by the participants to summarize the long-term evaluation of the whole WeChat-PBL experience after the 3-month clerkship. Data from the PBL cases, WeChat messages, periodic evaluations, and long-term evaluations were collected for analysis. RESULTS: There were 45 cases presented in the WeChat-PBL within the 3-month clerkship. All students had positive reactions to the communication within the PBL groups. The results of the periodic evaluation showed that the students and tutors were quite satisfied with the process of WeChat-PBL and appreciated the group members' contributions and performance. The final questionnaire results indicated that the WeChat-PBL had achieved positive effects. CONCLUSIONS: The results of this study indicate the feasibility and acceptability of the app, WeChat, for problem-based learning in a dental practical clerkship.

Anti-Inflammatory Activities and Related Mechanism of Polysaccharides Isolated from Sargentodoxa cuneata.

Sargentodoxa cuneata decoction has been used to treat arthritis in China for hundreds of years. Herein, the polysaccharide fraction (PSC) purified from S. cuneata was evaluated for its in vitro and in vivo anti-inflammatory effects. PSC and its sub-fractions PSCA-1 and PSCB-1 significantly suppressed nitric oxide (NO) release in LPS-induced RAW264.7 cells by down regulating the inducible nitric oxide synthase (iNOS) level. Furthermore, PSC markedly inhibited carrageenan induced rat hind paw edema, decreased in hind paw, serum and liver malondialdehyde (MDA) levels and prostaglandin E2 (PGE2 ) levels. In addition, PSC increased superoxide dismutase (SOD) activity in serum and liver of the rats. These results revealed that the polysaccharide obtained from S. cuneata (PSC) possessed potent anti-inflammatory activity and may be one of the important bioactive constituents from the plant responsible for the anti-arthritis effect.

[Correlation of the single nucleotide polymorphism rs662 of PON1 with the risk of male infertility].

Objective: To investigate the correlation between the single nucleotide polymorphism (SNP) rs662 of the paraoxonase 1 gene (PON1) and the risk of male infertility. METHODS: This case-control study included 403 male idiopathic infertility patients aged 29.00 ± 4.48 years in the case group and 329 normal fertile men aged 28.28 ± 4.08 years as healthy controls. We obtained DNA from the peripheral venous blood of the subjects, genotyped the SNP rs662 of PON1 by Sequenom MassArray, and analyzed the association between different genotypes of PON1 rs662 and male infertility using the logistic regression model. RESULTS: Compared with the normal controls, the infertility patients showed a significantly increased level of follicle-stimulating hormone (FSH) (ï¼»16.30 ± 17.76ï¼½ vs ï¼»4.72 ± 2.51ï¼½ U/L, P < 0.01) but a decreased percentage of progressively motile sperm (PMS) (ï¼»7.40 ± 14.17ï¼½ % vs ï¼»41.93 ± 9.06ï¼½ %, P < 0.01) and sperm concentration (ï¼»2.74 ± 3.64ï¼½ vs ï¼»75.83 ± 63.66ï¼½ ×106/ml, P < 0.01). Statistically significant differences were not found in the other parameters between the two groups of subjects, nor in the correlation of male infertility with the heterozygous genotype GA versus the wild homozygous genotype GG (OR = 0.98, 95% CI: 0.63－1.53, P = 0.923) or the homozygous genotype AA versus the wild homozygous genotype GG (OR = 0.87, 95% CI: 0.56－1.34, P = 0.525). CONCLUSIONS: The SNP rs662 of PON1 was not correlated with male infertility, which, however, needs to be confirmed by further studies with larger samples from a larger area.

Anatomical variation of infra-pyloric artery origination: A prospective multicenter observational study (IPA-Origin).

OBJECTIVE: Infra-pyloric artery (IPA) is an important anatomical landmark in treatment of gastric cancer and is the key vessel for pylorus-preserving gastrectomy and subgroup of infra-pyloric lymph nodes. However, its anatomical variation is not thoroughly understood. Our study aimed to clarify the origination of the IPA. METHODS: We did this prospective, multicenter, open-label, observational study at gastric surgery departments of 34 hospitals in China. Gastric cancer patients aged 18 years or older and scheduled to undergo elective total or distal gastrectomy were assigned. During the surgery, IPA dissecting and exposing the origination point with photographs or video clips were required. The primary outcome was the origination of the IPA. Analysis of variance, χ2 tests and Fisher's tests were used to analyze the differences between groups. The study is registered at Clinicaltrials.gov (No. NCT03071237). RESULTS: Between May 8 and July 31, 2017, 429 patients were assigned for the study, and 419 (97.7%) patients had the IPA dissected and recorded through photograph or video and were included in the primary outcome analysis. The median age was 62 years old, and 73.7% were male. Among the patients, 78.5% received laparoscopic surgery. Single IPA origination was identified in 398 (95.0%) patients, including gastroduodenal artery (GDA) in 154 (36.8%) patients, anterior superior pancreaticoduodenal artery (ASPDA) in 130 (31.0%) patients, and right gastroepiploic artery (RGEA) in 114 (27.2%) patients. Fifteen (3.6%) patients were identified with multiple IPA and 6 (1.4%) patients were identified as IPA absence. The differences in the distribution of surgical approach (P=0.003) and geographic area (P=0.030) were statistically significant. No difference was shown in sex, age, gastrectomy type, tumor location, and clinical T, N and M stage. CONCLUSIONS: Our study found that the IPA originates from GDA, ASPDA and RGEA in similar proportions. Laparoscopic surgery may be more helpful in dissection of the IPA than open surgery.

Halobacterium litoreum sp. nov., isolated from a marine solar saltern.

Halophilic archaeal strain ZS-54-S2T was isolated from Zhoushan marine solar saltern, China. Cells were rod-shaped, Gram-stain-negative and formed red-pigmented colonies on an agar plate. Strain ZS-54-S2T was able to grow at 20-50 °C (optimum 35 °C), at 1.7-4.8 M NaCl (optimum 3.9 M), at 0.005-1.0 M MgCl2 (optimum 0.05 M) and at pH 5.0-9.5 (optimum pH 7.0). The cells lysed in distilled water and the minimal NaCl concentration to prevent cell lysis was found to be 5 % (w/v). The major polar lipids of the strain were phosphatidic acid, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, two glycolipids, which were chromatographically identical to sulfated galactosyl mannosyl galactofuranosyl glucosyl diether and galactosyl mannosyl glucosyl diether, and an unidentified glycolipid, which was chromatographically identical to one detected in Halobacterium salinarum ATCC 33171T. The 16S rRNA gene and rpoB' gene of strain ZS-54-S2T were phylogenetically related to the corresponding genes of Halobacterium noricense JCM 15102T (97.5 % and 90.6 % relatedness, respectively), Halobacterium jilantaiense CGMCC 1.5337T (96.9 and 91.2 %), Halobacterium rubrum CGMCC 1.12575T (96.8 and 90.3 %) and Halobacterium salinarum CGMCC 1.1958T (96.5 and 88.4 %). The DNA G+C content of strain ZS-54-S2T was 66.7 mol%. The phenotypic, chemotaxonomic and phylogenetic properties suggested that strain ZS-54-S2T (=CGMCC 1.12562T=JCM 30038T) represents a new species of Halobacterium, for which the name Halobacteriumlitoreum sp. nov. is proposed.

Hyaluronic acid-coated, prodrug-based nanostructured lipid carriers for enhanced pancreatic cancer therapy.

CONTEXT: Gemcitabine (GEM) and Baicalein (BCL) are reported to have anti-tumor effects including pancreatic cancer. Hyaluronic acid (HA) can bind to over-expressed receptors in various kinds of cancer cells. OBJECTIVE: The aim of this study is to develop prodrugs containing HA, BCL and GEM, and construct nanomedicine incorporate GEM and BCL in the core and HA on the surface. This system could target the cancer cells and co-deliver the drugs. METHODS: GEM-stearic acid lipid prodrug (GEM-SA) and hyaluronic acid-amino acid-baicalein prodrug (HA-AA-BCL) were synthesized. Then, GEM and BCL prodrug-based targeted nanostructured lipid carriers (HA-GEM-BCL NLCs) were prepared by the nanoprecipitation technique. The in vitro cytotoxicity studies of the NLCs were evaluated on AsPC1 pancreatic cancer cell line. In vivo anti-tumor effects were observed on the murine-bearing pancreatic cancer model. RESULTS: HA-GEM-BCL NLCs were effective in entering pancreatic cancer cells over-expressing HA receptors, and showed cytotoxicity of tumor cells in vitro. In vivo study revealed significant tumor growth inhibition ability of HA-GEM-BCL NLCs in murine pancreatic cancer model. CONCLUSION: It could be concluded that HA-GEM-BCL NLCs could be featured as promising co-delivery, tumor-targeted nanomedicine for the treatment of cancers.

Methylation-associated silencing of miR-495 inhibit the migration and invasion of human gastric cancer cells by directly targeting PRL-3.

Phosphatase of regenerating liver-3 (PRL-3) is believed to be associated with cell motility, invasion, and metastasis. Our previous work found that PRL-3 is highly overexpressed in gastric cancer (GC) tissue with peritoneal metastasis and directly involved in the pathogenesis of GC peritoneal metastasis. Moreover, we further found that the down-regulation of endogenous miR-495 expression plays a causative role in over expression of PRL-3 in GC peritoneal metastasis. However, the molecular regulation mechanisms by which endogenous miR-495 expression is down-regulated and PRL-3 promotes GC peritoneal metastasis remain to be clearly elucidated. Some studies have shown that the promoter methylation is closely related to the miRNA gene expression. Therefore, in present study, based on our previous findings, we will analysis whether DNA methylation is a major cause of the down-expression of endogenous miR-495, which results in PRL-3 overexpression in GC peritoneal metastasis. Methylation specific PCR (MSP) and sodium bisulfite sequencing method (BSP) detected miR-495 gene promoter methylation status. We treated GC cell lines with 5-Aza-2'-deoxycytidine (5-Aza-dC) to make the gene promoter methylation inactivation. By treating with 5-Aza-dC the migration and invasion of GC cells were significantly inhibited. And the miR-495 was overexpressing, corresponds to the mRNA and protein levels of PRL-3 were reduced, the ability of invasion and metastasis was inhibited. This study suggest that miR-495 have tumor suppressor properties and are partially silenced by DNA hypermethylation in GC, will provide new strategies for prevention and treatment of GC peritoneal metastasis.

Halovenus rubra sp. nov., isolated from salted brown alga Laminaria.

Halophilic archaeal strain R28(T) was isolated from the brown alga Laminaria produced at Dalian, Liaoning Province, China. The cells of the strain were pleomorphic and lysed in distilled water, stained Gram-negative, and formed red-pigmented colonies. Strain R28(T) was able to grow at 25-50 °C (optimum 42 °C), in the presence of 3.1-5.1 M NaCl (optimum 3.9 M NaCl), with 0.005-1.0 M MgCl(2) (optimum 0.01 M MgCl(2)) and at pH 6.0-9.5 (optimum pH 7.0-7.5). The minimal NaCl concentration to prevent cell lysis was 15 % (w/v). The major polar lipids of the strain were identified as phosphatidic acid, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, and two glycolipids chromatographically identical to those of Halovenus aranensis CGMCC 1.11001(T). The 16S rRNA gene and rpoB' gene of strain R28(T) were phylogenetically related to the corresponding genes of Hvn. aranensis CGMCC 1.11001(T) (91.9-97.2 and 82.9 % nucleotide identity, respectively). The DNA G+C content of strain R28(T) was determined to be 56.3 mol%. The phenotypic, chemotaxonomic, and phylogenetic properties suggest that strain R28(T) (=CGMCC 1.10592(T) = JCM 17269(T)) represents a novel species of the genus Halovenus, for which the name Halovenus rubra sp. nov. is proposed.

Segmental Duodenectomy in Surgical Therapy of Tumor of the Third and Fourth Portions of Duodenum.

BACKGROUND/AIMS: To analyze our experience of segmental duodenectomy for tumors located at the third and fourth portion of the duodenum and attempt to explore the security and feasibility of this surgical procedure. METHODOLOGY: A retrospective cohort study of five patients who underwent segmental duodenectomy in our hospital, medical records were analyzed in this study. RESULTS: The initial symptoms in five patients are not specific. Five were surgically treated by segmental resection. All patients without postoperative anastomotic leakage, the gastroparesis and anastomotic stenosis each appeared in a case and all recovered after supportive care. Pathological examination showed: 3 cases of stromal tumor, 1 :ases of lymphangioma, diffuse large B-cell lymphoma. Postoperative gastrointestinal bleeding does not appear in the lymphangioma,two cases of high risk group of stromal tumor patients received targeting therapy with Imatinib Mesylate for 2 years after resection, the patient with lymphoma administer postoperative adjuvant chemotherapy. All patients are still alive and the lymphoma patient developed postoperative local recurrence after approximately six months. CONCLUSIONS: Segmental duodenectomy is a reliable and curative option for most duodenal benign tumor and stromal tumor located at the third and fourth portion. It is also applicable to some malignant tumor.

[Changes of CD4 + CD25 + Foxp3 + regulatory T cells in the peripheral blood and their correlation with insulin resistance in different stages of prostate cancer].

OBJECTIVE: To investigate the changes of CD4 + CD25 + Foxp3 + regulatory T cells in the peripheral blood mononuclear cells (PBMC) and their association with insulin resistance in different stages of prostate cancer (PCa). METHODS: Using flow cytometry, we counted the CD4+ CD25 + Foxp3 + regulatory T cells in the PBMCs of 62 PCa patients (5 cases of TNM stage I, 16 cases of stage II, 21 cases of stage III, and 20 cases of stage IV) and 42 normal healthy controls, and calculated their proportion in the CD4+ T-lymphocytes. We determined the levels of fast blood glucose (FBG) and fast insulin (FINS) for the insulin resistance index (HOMA-IR), obtained the serum IGF-1 level by ELISA, and analyzed the relationship of the count and proportion of CD4+ CD25+ Foxp3+ regulatory T cells with insulin resistance by comparison between the PCa patients and normal healthy controls. RESULTS: Compared with the control group, the PCa patients showed significantly increased HOMA-IR (3.68 ± 1.42 vs 6.68 ± 1.66), decreased level of serum IGF-1 ([164.56 ± 30.58] vs [96.39 ± 21.21] ng/ml), and elevated count ([1.99 ± 0.78 ] x 10(7) vs [3.55 ± 0.29] x 10(7)) and proportion ([5.33 ± 0.65] vs [13.88 ± 0.96]%) of CD4 + CD25 + Foxp3 regulatory T cells in the PBMCs. The TNM stage was correlated positively with the count and percentage of CD4 + CD25+ Foxp3 + regulatory T cells and HOMA-IR, but negatively with the level of serum IGF-1. Meanwhile, the count and percentage of CD4 + CD25 + Foxp3 + regulatory T cells were found to have a positive correlation with HOMA-IR (r = 0.722 and 0.689, P < 0.01) but a negative correlation with the level of serum IGF-1 (r = -0.747 and -0.896, P < 0.01). CONCLUSION: The count and proportion of CD4+ CD25 + Foxp3 + regulatory T cells in the peripheral blood and insulin resistance increase with the elevated stage of PCa. CD4 + CD25 + Foxp3 + regulatory T cells may be involved in the occurrence and progression of PCa by regulating insulin resistance.

Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration.

OBJECTIVE: To evaluate the 24-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly or as needed (pro re nata [PRN]) in patients with neovascular age-related macular degeneration (wet AMD). DESIGN: Twenty-four-month, multicenter, randomized, double-masked, active treatment-controlled phase 3 trial. PARTICIPANTS: Patients (n = 1098) ≥ 50 years of age with treatment-naïve subfoveal wet AMD. METHODS: Patients were randomized to receive intravitreal injections of ranibizumab 0.5 mg or 2.0 mg monthly or PRN after 3 monthly loading doses. MAIN OUTCOME MEASURES: The primary efficacy end point was the mean change in best-corrected visual acuity (BCVA) from baseline at month 12. Key secondary end points included mean change in BCVA from baseline at month 24, proportion of patients who gained ≥ 15 letters in BCVA, mean number of ranibizumab injections, and mean change in central foveal thickness from baseline over time by spectral-domain optical coherence tomography. Ocular and systemic safety events also were evaluated through month 24. RESULTS: At month 24, the mean change from baseline in BCVA was (letters) +9.1 (0.5 mg monthly), +7.9 (0.5 mg PRN), +8.0 (2.0 mg monthly), and +7.6 (2.0 mg PRN). The change in mean BCVA from month 12 to 24 was (letters) -1.0, -0.3, -1.2, and -1.0, respectively. The proportion of patients who gained ≥ 15 letters from baseline in BCVA at month 24 was 34.5%, 33.1%, 37.6%, and 34.8%, respectively. The mean number of ranibizumab injections through month 24 was 21.4, 13.3, 21.6, and 11.2, respectively; 5.6 and 4.3 mean injections were required in year 2 in the 0.5 mg and 2.0 mg PRN groups, respectively. The average treatment interval in the 0.5 mg PRN group was 9.9 weeks after 3 monthly loading doses, and 93% of these patients did not require monthly dosing. Ocular and systemic safety profiles over 2 years were similar among all 4 treatment groups and were consistent with previous ranibizumab trials in AMD. CONCLUSIONS: At month 24, mean BCVA improvements were clinically meaningful and similar among all 4 ranibizumab treatment groups. The 0.5 mg PRN group achieved a mean gain of 7.9 letters at month 24 with an average of 13.3 injections (5.6 injections in year 2). No new safety events were identified over 24 months.

Halopenitus salinus sp. nov., isolated from the brine of salted brown alga Laminaria.

A halophilic archaeal strain, SKJ47(T), was isolated from a commercial preparation of the brown alga Laminaria produced at Dalian, Liaoning Province, China. Cells of the strain were observed to be short rods, stain Gram-negative, and to form red-pigmented colonies on solid media. Strain SKJ47(T) was found to be able to grow at 20-50 °C (optimum 37 °C), at 0.9-4.8 M NaCl (optimum 2.6-3.1 M), at pH 6.0-9.5 (optimum pH 7.0). The cells lysed in distilled water and the minimal NaCl concentration to prevent cell-lysis was found to be 5% (w/v). The major polar lipids of the strain were identified as phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and two glycolipids chromatographically identical to those of Halopenitus persicus IBRC 10041(T). The 16S rRNA gene and rpoB' gene of strain SKJ47(T) were found to be phylogenetically related to the corresponding genes of Halopenitus malekzadehii IBRC-M 10418(T) (96.3 and 91.9% nucleotide identity, respectively) and Hpt. persicus IBRC 10041(T) (96.2 and 93.8%). The DNA G+C content of strain SKJ47(T) was determined to be 65.0 mol%. The phenotypic, chemotaxonomic and phylogenetic properties suggested that strain SKJ47(T) (=CGMCC 1.12229(T) = JCM 18641(T)) represents a new species of the genus Halopenitus, for which the name Halopenitus salinus sp. nov. is proposed.

Halobellus litoreus sp. nov., a halophilic archaeon isolated from a Chinese marine solar saltern.

Halophilic archaeal strain GX31(T) was isolated from a marine solar saltern of China. The cells of the strain were rod-shaped and lysed in distilled water, stain Gram-negative and formed red-pigmented colonies. It was neutrophilic, and required at least 0.9 M NaCl and 0-1.0 M MgCl2 for growth under the optimum growth temperature of 37 °C. The major polar lipids of the strain were phosphatidylglycerol (PG), PG phosphate methyl ester, PG sulphate, and two major glycolipids chromatographically identical to sulphated mannosyl glucosyl diether (S-DGD-1) and mannosyl glucosyl diether (DGD-1), respectively. Trace amounts of two unidentified lipids were also detected. On the basis of 16S rRNA gene sequence analysis, strain GX31(T) was closely related to the members of Halobellus of the family Halobacteriaceae with similarities of 94.1-98.7 %. Strain GX31(T) showed 89.8-95.4 % of the rpoB' gene similarity to the members of Halobellus. The DNA G+C content of strain GX31(T) was 66.8 mol%. Strain GX31(T) showed low DNA-DNA relatedness with two most related members of the genus Halobellus. The phenotypic, chemotaxonomic and phylogenetic properties suggest that strain GX31(T) represent a novel species of the genus Halobellus, for which the name Halobellus litoreus sp. nov. is proposed. The type strain is GX31(T) (=CGMCC 1.10387(T) = JCM 17118(T)).