Publications by authors named "Bo Tu"

119 Publications

Reversal of the CD8 T-Cell Exhaustion Induced by Chronic HIV-1 Infection Through Combined Blockade of the Adenosine and PD-1 Pathways.

Front Immunol 2021 10;12:687296. Epub 2021 Jun 10.

Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

Background: Targeting immune checkpoints for HIV treatment potentially provides a double benefit resulting from the ability to restore viral-specific CD8 T-cell functions and enhance HIV production from reservoir cells. Despite promising pre-clinical data, PD-1 blockade alone in HIV-1-infected patients with advanced cancer has shown limited benefits in controlling HIV, suggesting the need for additional targets beyond PD-1. CD39 and PD-1 are highly co-expressed on CD8 T cells in HIV-1 infection. However, the characteristics of CD39 and PD-1 dual-positive CD8 T-cell subsets in chronic HIV-1 infection remain poorly understood.

Methods: This study enrolled 72 HIV-1-infected patients, including 40 treatment naïve and 32 ART patients. A total of 11 healthy individuals were included as controls. Different subsets of CD8 T cells defined by CD39 and/or PD-1 expression were studied by flow cytometry. The relationships between the frequencies of the different subsets and parameters indicating HIV-1 disease progression were analyzed. Functional (i.e., cytokine secretion, viral inhibition) assays were performed to evaluate the impact of the blockade of adenosine and/or PD-1 signaling on CD8 T cells.

Results: The proportions of PD-1, CD39, and PD-1CD39 CD8 T cells were significantly increased in treatment naïve patients but were partially lowered in patients on antiretroviral therapy. In treatment naïve patients, the proportions of PD-1CD39 CD8 T cells were negatively correlated with CD4 T-cell counts and the CD4/CD8 ratio, and were positively correlated with viral load. CD39CD8 T cells expressed high levels of the A2A adenosine receptor and were more sensitive to 2-chloroadenosine-mediated functional inhibition than their CD39 counterparts. , a combination of blocking CD39/adenosine and PD-1 signaling showed a synergic effect in restoring CD8 T-cell function, as evidenced by enhanced abilities to secrete functional cytokines and to kill autologous reservoir cells.

Conclusion: In patients with chronic HIV-1 infection there are increased frequencies of PD-1, CD39, and PD-1CD39 CD8 T cells. In treatment naïve patients, the frequencies of PD-1CD39 CD8 T cells are negatively correlated with CD4 T-cell counts and the CD4/CD8 ratio and positively correlated with viral load. Combined blockade of CD39/adenosine and PD-1 signaling may exert a synergistic effect in restoring CD8 T-cell function in HIV-1-infected patients.
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http://dx.doi.org/10.3389/fimmu.2021.687296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222537PMC
June 2021

SIRT7: a sentinel of genome stability.

Open Biol 2021 Jun 16;11(6):210047. Epub 2021 Jun 16.

Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Shenzhen University International Cancer Center, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, Shenzhen 518055, People's Republic of China.

SIRT7 is a class III histone deacetylase that belongs to the sirtuin family. The past two decades have seen numerous breakthroughs in terms of understanding SIRT7 biological function. We now know that this enzyme is involved in diverse cellular processes, ranging from gene regulation to genome stability, ageing and tumorigenesis. Genomic instability is one hallmark of cancer and ageing; it occurs as a result of excessive DNA damage. To counteract such instability, cells have evolved a sophisticated regulated DNA damage response mechanism that restores normal gene function. SIRT7 seems to have a critical role in this response, and it is recruited to sites of DNA damage where it recruits downstream repair factors and directs chromatin regulation. In this review, we provide an overview of the role of SIRT7 in DNA repair and maintaining genome stability. We pay particular attention to the implications of SIRT7 function in cancer and ageing.
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http://dx.doi.org/10.1098/rsob.210047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205529PMC
June 2021

Targeting glucose metabolism sensitizes pancreatic cancer to MEK inhibition.

Cancer Res 2021 Jun 11. Epub 2021 Jun 11.

Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center

Pancreatic ductal adenocarcinoma (PDAC) is almost universally lethal. A critical unmet need exists to explore essential susceptibilities in PDAC and identify druggable targets to improve PDAC treatment. KRAS mutations dominate the genetic landscape of PDAC and lead to activation of multiple downstream pathways and cellular processes. Here, we investigated the requirement of these pathways for tumor maintenance using an inducible KrasG12D-driven PDAC mouse model (iKras model), identifying that RAF-MEK-MAPK signaling is the major effector for oncogenic KRAS-mediated tumor maintenance. However, consistent with previous studies, MEK inhibition had minimal therapeutic effect as a single agent for PDAC in vitro and in vivo. Although MEK inhibition partially downregulated transcription of glycolysis genes, it failed to suppress glycolytic flux in PDAC cells, which is a major metabolic effector of oncogenic KRAS. Accordingly, an in vivo genetic screen identified multiple glycolysis genes as potential targets that may sensitize tumor cells to MEK inhibition. Inhibition of glucose metabolism with low dose 2-deoxyglucose in combination with a MEK inhibitor induced apoptosis in KrasG12D-driven PDAC cells in vitro. The combination also inhibited xenograft PDAC tumor growth and prolonged overall survival in a genetically engineered PDAC mouse model. Molecular and metabolic analyses indicated that co-targeting glycolysis and MAPK signaling results in apoptosis via induction of lethal ER stress. Together, our work suggests that combined inhibition of glycolysis and the MAPK pathway may serve as an effective approach to target KRAS-driven PDAC.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3792DOI Listing
June 2021

Human umbilical cord mesenchymal stem cell transfusion in immune non-responders with AIDS: a multicenter randomized controlled trial.

Signal Transduct Target Ther 2021 Jun 9;6(1):217. Epub 2021 Jun 9.

Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

We examined the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) infusion for immune non-responder (INR) patients with chronic HIV-1 infection, who represent an unmet medical need even in the era of efficient antiretroviral therapy (ART). Seventy-two INR patients with HIV were enrolled in this phase II randomized, double-blinded, multicenter, placebo-controlled, dose-determination trial (NCT01213186) from May 2013 to March 2016. They were assigned to receive high-dose (1.5 × 10/kg body weight) or low-dose (0.5 × 10/kg body weight) hUC-MSC, or placebo. Their clinical and immunological parameters were monitored during the 96-week follow-up study. We found that hUC-MSC treatment was safe and well-tolerated. Compared with baseline, there was a statistical increase in CD4+ T counts in the high-dose (P < 0.001) and low-dose (P < 0.001) groups after 48-week treatment, but no change was observed in the control group. Kaplan-Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group (95.8% vs. 70.8%, P = 0.004). However, no significant changes in CD4/CD8+ T counts and CD4/CD8 ratios were observed among the three groups. In summary, hUC-MSC treatment is safe. However, the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.
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http://dx.doi.org/10.1038/s41392-021-00607-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187429PMC
June 2021

Compromised long-lived memory CD8 T cells are associated with reduced IL-7 responsiveness in HIV-infected immunological nonresponders.

Eur J Immunol 2021 May 11. Epub 2021 May 11.

Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long-lived memory CD8 T cells (LLMCs) are essential executors of long-term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological nonresponders (INRs). We found that both TNs and INRs showed severely compromised LLMCs compared with HCs and CRs, respectively. The decrease of LLMCs in TNs correlated positively with the reduction of their precursors, namely memory precursor effector T cells (MPECs), which might be associated with elevated pro-inflammatory cytokines. Strikingly, INRs showed an accumulation of MPECs, which exhibited diminished responsiveness to interleukin 7 (IL-7), thereby indicating abrogated differentiation into LLMCs. Moreover, in vitro studies showed that treatment with dexamethasone could improve the IL7-phosphorylated (p)-signal transducer and activator of transcription (STAT5) response by upregulating the expression of the interleukin 7 receptor (IL-7Rα) on MPECs in INRs. These findings provide insights that will encourage the development of novel therapeutics to improve immune function in PLWH.
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http://dx.doi.org/10.1002/eji.202149203DOI Listing
May 2021

HLA-mismatched allogeneic adoptive immune therapy in severely immunosuppressed AIDS patients.

Signal Transduct Target Ther 2021 May 7;6(1):174. Epub 2021 May 7.

Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, PLA General Hospital, Beijing, China.

Severely immunosuppressed AIDS patients with recurrent opportunistic infections (OIs) represent an unmet medical need even in the era of antiretroviral therapy (ART). Here we report the development of a human leukocyte antigen (HLA)-mismatched allogeneic adaptive immune therapy (AAIT) for severely immunosuppressed AIDS patients. Twelve severely immunosuppressed AIDS patients with severe OIs were enrolled in this single-arm study. Qualified donors received subcutaneous recombinant granulocyte-colony-stimulating factor twice daily for 4-5 days to stimulate hematopoiesis. Peripheral blood mononuclear cells were collected from these donors via leukapheresis and transfused into the coupled patients. Clinical, immunological, and virological parameters were monitored during a 12-month follow-up period. We found AAIT combined with ART was safe and well-tolerated at the examined doses and transfusion regimen in all 12 patients. Improvements in clinical symptoms were evident throughout the study period. All patients exhibited a steady increase of peripheral CD4 T cells from a median 10.5 to 207.5 cells/μl. Rapid increase in peripheral CD8 T-cell count from a median 416.5 to 1206.5 cells/μl was found in the first 90 days since initiation of AAIT. In addition, their inflammatory cytokine levels and HIV RNA viral load decreased. A short-term microchimerism with donor cells was found. There were no adverse events associated with graft-versus-host disease throughout the study period. Overall, AAIT treatment was safe, and might help severely immunosuppressed AIDS patients to achieve a better immune restoration. A further clinical trial with control is necessary to confirm the efficacy of AAIT medication.
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http://dx.doi.org/10.1038/s41392-021-00550-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102474PMC
May 2021

Dihydromyricetin Exhibits Antitumor Activity in Nasopharyngeal Cancer Cell Through Antagonizing Wnt/β-catenin Signaling.

Integr Cancer Ther 2021 Jan-Dec;20:1534735421991217

The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.

Background: Cancer stem cells (CSCs) have been demonstrated to play a vital role in a diversity of biological processes in cancers. With the emergence of new evidence, the important function of CSCs in the formation of multidrug resistance of nasopharyngeal cancer has been demonstrated. Dysregulated Wnt/β-catenin signaling pathway is an important contributor to chemoresistance and maintenance of CSCs-like characteristics. This research aims to investigate comprehensively the function of dihydromyricetin (DMY), a natural flavonoid drug, on the cisplatin (cis) resistance and stem cell properties of nasopharyngeal cancer.

Methods: In this study, the functional role of DMY in nasopharyngeal cancer progression was comprehensively investigated in vitro and in vivo, and then its relationship with CSCs-like phenotypes and multiple oncogenes was analyzed.

Results: In parallel assays, the growth inhibitory action of cis was enhanced by the addition of DMY in cis-resistant nasopharyngeal cancer cell lines (Hone1/cis and CNE1/cis). Functional assays showed that DMY markedly diminished the stem cell properties of nasopharyngeal cells, such as colony and tumor-sphere formation. In vivo data showed that the growth of Hone1 CSCs formed tumor xenograft was inhibited significantly by the administration of DMY. Additionally, DMY could impair the Wnt/β-catenin signaling pathway and regulate the expression of downstream proteins in nasopharyngeal cancer cells.

Conclusions: Our study clarified the anti-tumor activity of DMY through blocking the Wnt/β-catenin signaling pathway in nasopharyngeal cancer. Therefore, DMY could be a novel therapeutic agent for nasopharyngeal cancer treatment.
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http://dx.doi.org/10.1177/1534735421991217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975991PMC
March 2021

NLRP3 inflammasome induces CD4+ T cell loss in chronically HIV-1-infected patients.

J Clin Invest 2021 Mar;131(6)

Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

Chronic HIV-1 infection is generally characterized by progressive CD4+ T cell depletion due to direct and bystander death that is closely associated with persistent HIV-1 replication and an inflammatory environment in vivo. The mechanisms underlying the loss of CD4+ T cells in patients with chronic HIV-1 infection are incompletely understood. In this study, we simultaneously monitored caspase-1 and caspase-3 activation in circulating CD4+ T cells, which revealed that pyroptotic and apoptotic CD4+ T cells are distinct cell populations with different phenotypic characteristics. Levels of pyroptosis and apoptosis in CD4+ T cells were significantly elevated during chronic HIV-1 infection, and decreased following effective antiretroviral therapy. Notably, the occurrence of pyroptosis was further confirmed by elevated gasdermin D activation in lymph nodes of HIV-1-infected individuals. Mechanistically, caspase-1 activation closely correlated with the inflammatory marker expression and was shown to occur through NLRP3 inflammasome activation driven by virus-dependent and/or -independent ROS production, while caspase-3 activation in CD4+ T cells was more closely related to T cell activation status. Hence, our findings show that NLRP3-dependent pyroptosis plays an essential role in CD4+ T cell loss in HIV-1-infected patients and implicate pyroptosis signaling as a target for anti-HIV-1 treatment.
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http://dx.doi.org/10.1172/JCI138861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954596PMC
March 2021

Efficacy of ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis or occlusion at juxta-anastomosis: A 3-year follow-up cohort study.

J Vasc Surg 2021 Jul 16;74(1):217-224. Epub 2020 Dec 16.

Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Objective: Arteriovenous fistula (AVF) is the preferred access for hemodialysis. Percutaneous transluminal angioplasty (PTA) has become a choice for AVF stenosis, and ultrasound has been used in PTA more frequently.

Methods: This single-center retrospective cohort study analyzed 129 patients who underwent PTA in the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2016. Angioplasty was performed using a noncompliant high-pressure balloon. The process was visualized by duplex scan. Our inclusion criteria were as follows: (1) stenoses or occlusions were located at the juxta-anastomosis site: the first 5 cm of the vein distal to the anastomosis; (2) stenosis was confirmed with the following conditions: (a) flow rates are <500 mL/min in the brachial artery and <200 mL/min in the fistula during dialysis, and (b) the stenosis diameter is <1.7 mm. We used the Kaplan-Meier curve to show the postintervention primary and secondary patency rates of patients with stenosis and occlusion.

Results: Altogether, 129 patients with 76 males were analyzed. Moreover, 104 have AVFs on the left arm, and only one patient had an ulnar-basilic AVF, whereas others had a radial-cephalic AVF. The postintervention primary patency rates are better in occlusion cases (P < .05), whereas secondary patency rates have no difference. The postintervention primary patency rates are better in patients without diabetes mellitus (P < .05), whereas the secondary patency rates had no difference.

Conclusions: For juxta-anastomosis site stenosis or occlusion, PTA can be used to obtain satisfactory results.
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http://dx.doi.org/10.1016/j.jvs.2020.11.041DOI Listing
July 2021

Nickel-Catalyzed Amination of Aryl Chlorides with Amides.

Org Lett 2021 Feb 18;23(3):687-691. Epub 2020 Dec 18.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, China.

A nickel-catalyzed amination of aryl chlorides with diverse amides via C-N bond cleavage has been realized under mild conditions. A broad substrate scope with excellent functional group tolerance at a low catalyst loading makes the protocol powerful for synthesizing various aromatic amines. The aryl chlorides could selectively couple to the amino fragments rather than the carbonyl moieties of amides. Our protocol complements the conventional amination of aryl chlorides and expands the usage of inactive amides.
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http://dx.doi.org/10.1021/acs.orglett.0c03836DOI Listing
February 2021

Alterations of the frequency and functions of follicular regulatory T cells and related mechanisms in HIV infection.

J Infect 2020 11 19;81(5):776-784. Epub 2020 Sep 19.

Treatment and Research Center for Infectious Disease, The Fifth Medical Center of PLA General Hospital, NO. 100, Xisihuan Road, FengTai District, Beijing 100039, China. Electronic address:

Human immunodeficiency virus (HIV) infection impairs both cellular and humoral immune system. Follicular regulatory T (Tfr) cells are a recently characterised subset of CD4T cells. Tfr also exerts an immunosuppressive effect on humoral immune system through interaction with follicular helper T (Tfh) cells, but the role of Tfr in HIV infection needs to be further elucidated. 20 treatment-naïve and 20 antiretroviral therapy (ART)-treated HIV-infected individuals were enrolled for cross-sectional study and nine complete responders (CRs) and eight immune non-responders (INRs) after ART were collected for retrospective cohort study. Tfr phenotypes, cytokine secretions, and apoptosis of those subjects were evaluated by flow cytometry. HIV DNA was measured by reverse transcription-quantitative PCR (RT-qPCR). Significantly increased circulating Tfr was observed in chronic HIV patients and the imbalance between Tfr and Tfh17 was associated with CD4T counts. In addition, an elevated proportion of Tfr was associated with immune reconstruction failure of patients after ART. The IL-10 and CTLA-4 expressions of Tfr cells were up-regulated in treatment-naïve HIV patients. Ex vivo experiments showed IL-10 and CTLA-4 expressed by Tfr inhibited IL-21 secretion of Tfh. Tfr harboured a comparable HIV-1 DNA level with Tfh in HIV patients. Compared to Tfr of HCs, Tfr cells of HIV patients were more insensitive to CD95 and IFN-α induced apoptosis, had a higher proliferation rate, and had more stem-like T cell (Tscm) phenotype. The anti-apoptosis feature, higher proliferation rate, and Tscm-like features of Tfr in HIV patients, led to the expansion of Tfr which in turn resulted in dysfunction of Tfh. Tfr cells were also involved in immune reconstruction failure and latent infection of HIV. Tfr cells were a novel, and potentially therapeutic, target for the cure of HIV infection, especially for HIV vaccine development and HIV reservoir elimination.
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http://dx.doi.org/10.1016/j.jinf.2020.09.014DOI Listing
November 2020

Multivariate predictive model for asymptomatic spontaneous bacterial peritonitis in patients with liver cirrhosis.

World J Gastroenterol 2020 Aug;26(29):4316-4326

Department of Infectious Disease, the Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100039, China.

Background: Spontaneous bacterial peritonitis (SBP) is a detrimental infection of the ascitic fluid in liver cirrhosis patients, with high mortality and morbidity. Early diagnosis and timely antibiotic administration have successfully decreased the mortality rate to 20%-25%. However, many patients cannot be diagnosed in the early stages due to the absence of classical SBP symptoms. Early diagnosis of asymptomatic SBP remains a great challenge in the clinic.

Aim: To establish a multivariate predictive model for early diagnosis of asymptomatic SBP using positive microbial cultures from liver cirrhosis patients with ascites.

Methods: A total of 98 asymptomatic SBP patients and 98 ascites liver cirrhosis patients with negative microbial cultures were included in the case and control groups, respectively. Multiple linear stepwise regression analysis was performed to identify potential indicators for asymptomatic SBP diagnosis. The diagnostic performance of the model was estimated using the receiver operating characteristic curve.

Results: Patients in the case group were more likely to have advanced disease stages, cirrhosis related-complications, worsened hematology and ascites, and higher mortality. Based on multivariate analysis, the predictive model was as follows: y () = 0.018 + 0.312 × MELD (model of end-stage liver disease) + 0.263 × PMN (ascites polymorphonuclear) + 0.184 × N (blood neutrophil percentage) + 0.233 × HCC (hepatocellular carcinoma) + 0.189 × renal dysfunction. The area under the curve value of the established model was 0.872, revealing its high diagnostic potential. The diagnostic sensitivity was 73.5% (72/98), the specificity was 86.7% (85/98), and the diagnostic efficacy was 80.1%.

Conclusion: Our predictive model is based on the MELD score, polymorphonuclear cells, blood N, hepatocellular carcinoma, and renal dysfunction. This model may improve the early diagnosis of asymptomatic SBP.
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http://dx.doi.org/10.3748/wjg.v26.i29.4316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422546PMC
August 2020

Resolution of high-output cardiac failure secondary to high flow radiocephalic fistula by precision banding under ultrasound guidance: A case report.

J Vasc Access 2020 Aug 23:1129729820947858. Epub 2020 Aug 23.

Ultrasonography Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.

Background: The creation of dialysis shunt affects hemodynamic and cardiac function. High-output cardiac failure may occur if dialysis access volume flow is greater than 1500 to 2000 mls/min. To resolve symptoms of cardiac failure due to high flow dialysis shunt requires flow reduction procedure. We describe successful resolution of symptoms of heart failure due to excessive flow dialysis access by adopting precision banding, totally under vascular ultrasound guidance without angiography.

Case: Hemodialysis adult patient uses the right arm radiocephalic fistula for 4 years. Recently, the patient presented with symptoms of high-output cardiac failure, including dyspnea, palpitations, fatigue, and orthopnea. The cardiac unit excluded all other causes of cardiac failure and referred the patient to our center for further evaluation. Ultrasonography revealed high blood volume flow measuring 3100 mls/min at brachial artery, marking high flow fistula and the underlying cause of cardiac failure. Juxta-anastomotic segment of fistula vein was identified; 3 mm diameter balloon was advanced to the juxta-anastomotic segment and maximally inflated. Two precision bandings were made on this segment, 1 to 2 cm apart with flow reduction to 691 mls/min. All steps of the procedure were done under ultrasound guidance without angiography. All symptoms were significantly alleviated immediately following the procedure. The patient was discharged after 48 h of monitoring. At 6 months, the patient was stable, no recurrence of high flow access, no signs or symptoms of cardiac failure, and the flow was 1119 mls/min.

Conclusion: This case demonstrates that the precision banding procedure is feasible under ultrasound guidance, and the procedure is safe and effective in resolution of cardiac failure due to high flow radiocephalic fistula.
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http://dx.doi.org/10.1177/1129729820947858DOI Listing
August 2020

Radial artery diameterand and age related functional maturation of the radio-cephalic arteriovenous fistula.

BMC Nephrol 2020 06 22;21(1):234. Epub 2020 Jun 22.

Department of Nephrology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road NO.600, Guangzhou, 510632, China.

Background: Previous studies have not described the relationship between reducing radial artery diameter as well as increasing age and functional maturation of the radio-cephalic arteriovenous fistula (RCAVF) and no data identify these as linear relationship. The objective of this study was to perform trend analysis to assess these aspects.

Methods: Our retrospective cohort study enrolled and analyzed 353 follow-up cases that underwent first AVF creation. The artery and vein sizes were measured by ultrasound. We performed follow-up, a minimum of 3 months after surgery. Multivariable logistic regression analysis was used to identify independent risk factors inmaturation. Participant age was categorized into four groups (age ≤ 29, 30-49, 50-69, and 70-90 years). Radial artery diameter was categorized into four groups (≤ 1.9, >1.9 and ≤ 2.1, >2.1 and ≤ 2.4, >2.4 mm) according to median and interquartile ranges. We adjusted for confounders in four logistic models, and primary analyses were based on building ordered category models and tested P values for trends to estimate the relationship of radial artery diameter and each 20-year increase in age with risk of maturation.

Results: The mature RCAVF group included 301 cases, and the immature group included 52 cases. Radial artery diameter, age, and diabetes were independent risk factors of maturation. Odds ratios (ORs) associated with maturation reduced with increasing age, while ORs increased with increasing radial artery diameter. P values for trends(<0.05) were observed in all four models. A reduction in radial artery diameter and higher age were significantly associated with a higher incidence of immaturity after adjusting the multivariate models. The risks of immaturation were increased by more than 1.54 fold for each 20-year increase and increased by more than 1.34 fold for the smaller radial artery diameter group.

Conclusion: Our findings suggest that a significantly higher immaturity risk of RCAVF was associated with increasing age and a reduction in radial artery diameter. Our study identified a linear exposure-response relationship of age and radial artery diameter with immaturity incident. A careful selection of patients will be helpful in improving AVF functional maturation.
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http://dx.doi.org/10.1186/s12882-020-01883-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310035PMC
June 2020

gen. nov., sp. nov., an anaerobic formate-utilizing bacterium isolated from Shengli oilfield, and proposal of four novel families and ord. nov. in the phylum .

Int J Syst Evol Microbiol 2020 May;70(5):3361-3373

Institute of New Energy and Low-Carbon Technology, Sichuan University, Chengdu, 610065, PR China.

A novel obligately anaerobic, thermophilic and formate-utilizing bacterium K32 was isolated from Shengli oilfield of China. Cells were straight rods (0.4-0.8 µm × 2.5-8.0 µm), Gram-stain-positive, non-spore-forming and slightly motile. Optimum growth occurred with pH of 7 and 0.5 g l NaCl under temperature of 55-60 °C. Nitrate could be reduced into nitrite, syntrophic formate oxidation to methane and carbon dioxide occurred when co-culturing strain K32 and ΔH. The main cellular fatty acids were iso-C (24.0 %), anteiso-C (21.7 %), C (12.7 %) and C (10.8 %), and the main polar lipid was phosphatidylglycerol. The G+C content of the genomic DNA was 46.3 mol%. The 16S rRNA gene sequence of K32 shared ≤90.4 % of sequence similarity to closest type strains of , and members of the genus . Based on the phenotypic, biochemical and genotypic characterization, gen. nov., sp. nov. is proposed with K32 (=CCAM 584 =DSM 107278=CGMCC1.5297) as the type strain, which is the first representative of fam. nov. In addition, the order nd family were reclassified, and three novel families in the novel order of ord. nov. were also proposed.
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http://dx.doi.org/10.1099/ijsem.0.004178DOI Listing
May 2020

A simple tourniquet technique for bleeding control after percutaneous hemodialysis fistula and graft interventions.

BMC Nephrol 2020 03 31;21(1):112. Epub 2020 Mar 31.

Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: The purse-string suture has been widely used for bleeding control after percutaneous interventions through arteriovenous fistula (AVF) and graft (AVG), and it requires suture removal the next day. This study aimed to introduce a simple method using a tourniquet to facilitate hemostasis following AVF or AVG sheath removal after percutaneous procedures.

Methods: Data were retrospectively collected and included all the consecutive patients who received bleeding control with a tourniquet after percutaneous AVF or AVG interventions. Hemostasis was facilitated using the tourniquet technique after sheath removal.

Results: A total of 1966 patients who received the tourniquet technique for bleeding control after percutaneous AVF or AVG interventions were included. Bleeding control was successfully achieved in all patients. Regarding complications, hematoma, thrombosis, and rebleeding occurred in 57 (2.9%), 11 (0.6%), and 8 (0.4%) patients, respectively. Neither pseudoaneurysm nor infection occurred in the patients. Age, gender, pre-existing diseases (including diabetes and hypertension), procedure count, sheath size, hemodialysis access type, and canalization route were similar between patients with and without complications. The primary patency rates at 6,12, 24, and 36 months were 85.0, 64.6, 53.8, and 41.6%, respectively.

Conclusions: The tourniquet technique is an effective and safe approach for facilitating hemostasis after catheter-based percutaneous interventions of hemodialysis accesses.
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http://dx.doi.org/10.1186/s12882-020-01784-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110728PMC
March 2020

Virtual memory CD8+ T cells restrain the viral reservoir in HIV-1-infected patients with antiretroviral therapy through derepressing KIR-mediated inhibition.

Cell Mol Immunol 2020 12 24;17(12):1257-1265. Epub 2020 Mar 24.

Peking University 302 Clinical Medical School, Beijing, China.

The viral reservoir is the major hurdle in developing and establishing an HIV cure. Understanding factors affecting the size and decay of this reservoir is crucial for the development of therapeutic strategies. Recent work highlighted that CD8+ T cells are involved in the control of viral replication in ART-treated HIV-1-infected individuals, but how CD8+ T cells sense and restrict the HIV reservoir are not fully understood. Here, we demonstrate that a population of unconventional CD45RA+, PanKIR+, and/or NKG2A+ virtual memory CD8+ T cells (T cells), which confer rapid and robust protective immunity against pathogens, plays an important role in restraining the HIV DNA reservoir in HIV-1-infected patients with effective ART. In patients undergoing ART, T cells negatively correlate with HIV DNA and positively correlate with circulating IFN-α2 and IL-15. Moreover, T cells constitutively express high levels of cytotoxic granule components, including granzyme B, perforin and granulysin, and demonstrate the capability to control HIV replication through both cytolytic and noncytolytic mechanisms. Furthermore, by using an ex vivo system, we showed that HIV reactivation is effectively suppressed by T cells through KIR-mediated recognition. This study suggests that T cells are a promising target to predict posttreatment virological control and to design immune-based interventions to reduce the reservoir size in ART-treated HIV-1-infected individuals.
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http://dx.doi.org/10.1038/s41423-020-0408-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784989PMC
December 2020

Correlation of intensity-modulated radiation therapy at a specific radiation dose with the prognosis of nasal mucous damage after radiotherapy.

Radiat Environ Biophys 2020 05 6;59(2):245-255. Epub 2020 Feb 6.

Department of Oncology, The First Affiliated Hospital of Ji Nan University, No. 613 Huang Pu Road west, Guangzhou, 510632, Guangdong, China.

Objective of the present study was to investigate the tolerant radiation dose of nasal mucosa by observing and analyzing patients who received intensity-modulated radiation therapy (IMRT). Patients with nasopharyngeal carcinoma (N = 66) were selected for this study. The modified saccharin assay, endoscopy test, magnetic resonance imaging, and sino-nasal outcome test-20 (SNOT-20) survey were performed for the patients before and at 0 (T0), 3 (T1), 6 (T2), and 12 (T3) months after radiotherapy. The threshold doses of IMRT before radiotherapy and at T0, T1, T2, and T3 were determined as, respectively, 37 Gy, 37 Gy, 39 Gy, and 37 Gy for the saccharin test; 38 Gy, 37 Gy, 40 Gy, and 38 Gy for the endoscopy test; and 39 Gy, 37 Gy, 39 Gy, and 39 Gy for the nasal-related symptom scoring test. The modified saccharin assay, endoscopy test, and SNOT-20 survey revealed that a low dose (< threshold dose) of IMRT was associated with higher mucocilia transport rate (MRT), better endoscopy test score, and improved SNOT-20 score. The patients who received IMRT at a dose less than the threshold had the least damaged nasal mucosa morphology, and functional impairment scores were highest at T1 of IMRT. We conclude that nasal mucosa showed the most serious damage within 3 months after IMRT. If the radiation dose can be controlled within the threshold, the nasal mucosa can recover in the following few months, but recovery will be difficult otherwise.
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http://dx.doi.org/10.1007/s00411-020-00830-5DOI Listing
May 2020

Synergistic effects of vorinostat (SAHA) and azoles against Aspergillus species and their biofilms.

BMC Microbiol 2020 02 7;20(1):28. Epub 2020 Feb 7.

Department of Otorhinolaryngology and Head Neck Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, People's Republic of China.

Background: Invasive aspergillosis is a fungal infection that occurs mainly in immunocompromised patients. It is responsible for a high degree of mortality and is invariably unresponsive to conventional antifungal treatments. Histone deacetylase inhibitors can affect the cell cycle, apoptosis and differentiation. The histone deacetylase inhibitor vorinostat (SAHA) has recently received approval for the treatment of cutaneous T cell lymphoma. Here, we investigated the interactions of SAHA and itraconazole, voriconazole, and posaconazole against Aspergillus spp. in vitro using both planktonic cells and biofilms.

Results: We investigated 20 clinical strains using broth microdilution checkerboard methods. The results showed synergy between SAHA and itraconazole, voriconazole, and posaconazole against 60, 40, and 25% of tested isolates of planktonic Aspergillus spp., respectively. Similar synergy was also observed against Aspergillus biofilms. The expression of the azole-associated multidrug efflux pumps MDR1, MDR2, MDR3 and MDR4, as well as that of HSP90, was measured by RT-PCR. The results indicated that the molecular mechanism of the observed synergistic effects in Aspergillus fumigatus may be partly associated with dampened expression of the efflux pump genes and, furthermore, that HSP90 suppression may be a major contributor to the observed synergistic effects of the drugs.

Conclusions: SAHA has potential as a secondary treatment to enhance the effects of azoles against both biofilm and planktonic cells of Aspergillus spp. in vitro. This effect occurs mostly by inhibition of HSP90 expression.
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http://dx.doi.org/10.1186/s12866-020-1718-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006160PMC
February 2020

Efficacy and safety of a mother-child technique for recanalization of chronic central venous occlusive disease in hemodialysis patients.

J Vasc Surg Venous Lymphat Disord 2020 07 14;8(4):558-564. Epub 2019 Dec 14.

Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Objective: There is no optimal treatment for central vein occlusive disease that remains a major contributor to vascular access impairment. This study aimed to review the outcomes of percutaneous treatment with a mother-child technique in the treatment of symptomatic central venous stenosis (CVS) and central venous occlusion (CVO) in patients on hemodialysis.

Methods: Data were collected retrospectively and included all consecutive patients with CVS or CVO who were treated with percutaneous angioplasty and stenting. The occlusive lesions were crossed using the mother-child technique with an angiographic catheter-in-guiding catheter system.

Results: A total of 36 patients with symptomatic CVS and 45 patients with total CVO were included. The average age and gender composition were similar between the two groups. Patients with CVO had higher prevalence of diabetic nephropathy than CVS (24.4% vs 5.6%; P < .05). Lesion success, device success, and procedural success were achieved in 36 (100%), 1 (100%), and 36 (100%) patients in the CVS group and in 43 (95.6%), 11 (100%), and 43 (95.6%) patients in the CVO group, respectively. There were no severe complications or procedure-related deaths in either group. During follow-up (median, 6 months), the primary patency rates were 89.7% (CVS) and 81.0% (CVO) at 6 months and were 54.2% (CVS) and 47.1% (CVO) at 12 months. The assisted primary patency rates were 100% (CVS) and 91.2% (CVO) at 6 and 12 months.

Conclusions: With extra backup support of the mother-child technique, percutaneous treatment provides an effective and safe method for recanalization of chronic venous occlusion in patients on hemodialysis.
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http://dx.doi.org/10.1016/j.jvsv.2019.10.020DOI Listing
July 2020

gen. nov., sp. nov., an aerotorelant bacterium isolated from Shengli oilfield and validation of family .

Int J Syst Evol Microbiol 2020 Feb;70(2):951-957

Center for Anaerobic Microbial Resources of Sichuan Province, Chengdu, PR China.

A novel Gram-stain-positive, rod shaped and anaerobic bacterium, designated as W6, was isolated from Shengli oilfield in China. Strain W6 was observed to grow from 20 to 45 °C with pH 6.5-9.0 (optimally at 40 °C and pH of 7.5) and without addition of NaCl. The major cellular fatty acids were iso-C (29.1%), C (27.0%) and C (12.2%), and the main polar lipids were lipids (L) and aminolipids (AL). The DNA G+C content is 42.9 mol%. Based on 16S rRNA gene sequence analysis, strain W6 showed highest similarities to DSM 9508 (94.9%) and DSM 12858 (94.1%). The morphological, physiological, biochemical, phylogenetic and phylogenomic analyses demonstrated strain W6 (CCAM 534=DSM 28124=CGMCC 1.5291) represents a novel species in a new genus for which the name gen. nov. sp. nov. is proposed. The family is proposed as a new family containing the genera , , , , , , , and species based on the phylogenetic and phylogenomic analyses.
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http://dx.doi.org/10.1099/ijsem.0.003854DOI Listing
February 2020

YAP1 oncogene is a context-specific driver for pancreatic ductal adenocarcinoma.

JCI Insight 2019 11 1;4(21). Epub 2019 Nov 1.

Molecular and Cellular Oncology Department.

Transcriptomic profiling classifies pancreatic ductal adenocarcinoma (PDAC) into several molecular subtypes with distinctive histological and clinical characteristics. However, little is known about the molecular mechanisms that define each subtype and their correlation with clinical outcome. Mutant KRAS is the most prominent driver in PDAC, present in over 90% of tumors, but the dependence of tumors on oncogenic KRAS signaling varies between subtypes. In particular, the squamous subtype is relatively independent of oncogenic KRAS signaling and typically displays much more aggressive clinical behavior versus the progenitor subtype. Here, we identified that yes-associated protein 1 (YAP1) activation is enriched in the squamous subtype and associated with poor prognosis. Activation of YAP1 in progenitor subtype cancer cells profoundly enhanced malignant phenotypes and transformed progenitor subtype cells into squamous subtype. Conversely, depletion of YAP1 specifically suppressed tumorigenicity of squamous subtype PDAC cells. Mechanistically, we uncovered a significant positive correlation between WNT5A expression and YAP1 activity in human PDAC and demonstrated that WNT5A overexpression led to YAP1 activation and recapitulated a YAP1-dependent but Kras-independent phenotype of tumor progression and maintenance. Thus, our study identifies YAP1 oncogene as a major driver of squamous subtype PDAC and uncovers the role of WNT5A in driving PDAC malignancy through activation of the YAP pathway.
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http://dx.doi.org/10.1172/jci.insight.130811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948828PMC
November 2019

Description of gen. nov., sp. nov., and proposal of ord. nov. containing two novel families of fam. nov. and fam. nov.

Int J Syst Evol Microbiol 2019 Dec;69(12):3891-3902

China Collection of Anaerobic Microorganisms, Chengdu 610041, PR China.

A Gram-stain-negative, rod-shaped, chemoorganotrophic and anaerobic bacterium, strain SK-G1, was isolated from oily sludge sampled at the Shengli oilfield in PR China. Growth occurred with 0-30 g l NaCl, at 40-65 °C and at pH 6.0-8.5. The predominant fatty acids were C and C, and the major cellular polar lipids were phosphatidylglycerol and phosphatidylethanolamine. No respiratory quinone was detected. The genomic G+C content was 43.9 mol%. The strain had highest 16S rRNA gene sequence similarity (93.2 % identity) to DSM 15584. The phylogenetic, phenotypic and chemotaxonomic data showed that strain SK-G1 (=CCAM 530=KCTC 15783=JCM 33158) represents a novel species of a new genus gen. nov., sp. nov. The results of phylogenetic and phylogenomic analyses indicated that the genera , , , , , and formed a clade with high bootstrap support distinguishing to other taxon within the order Thermoanaerobacterales. This clade is proposed as ord. nov. and includes fam. nov. and fam. nov. Emended descriptions of the order and family are also provided.
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http://dx.doi.org/10.1099/ijsem.0.003701DOI Listing
December 2019

Comparative efficacy and safety of local and peripheral venous thrombolytic therapy with urokinase for thrombosed hemodialysis arteriovenous fistulas.

Exp Ther Med 2019 May 20;17(5):4279-4284. Epub 2019 Mar 20.

Department of Ultrasonography, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, P.R. China.

Arteriovenous fistula (AVF) thrombosis is a common complication in patients undergoing hemodialysis, and early intervention is required. Urokinase has been used as a thrombolytic agent for declotting the thrombosed access. However, the optimal route for infusing urokinase remains to be determined. In the present retrospective observational study, 49 patients who underwent local venous infusion and 57 patients with peripheral venous infusion of urokinase were included. A urokinase dosage of 300,000 U was administered until successful thrombolysis, which was a maximum of three times. Age, sex, period of dialysis, time of AVF placement, systolic and diastolic blood pressure and thrombus age were similar between the two groups. The efficacy of urokinase infusion via the two routes in resolving thrombosed AVFs, defined as successful fibrinolysis, and the safety, defined as the number of bleeding events, was compared. The cumulative thrombolysis success rate following three sessions of thrombolytic therapy in the local venous thrombolysis group was higher compared with that in the peripheral venous thrombolysis group (85.7 vs. 68.4%; P=0.04). The local thrombolysis group exhibited less ecchymosis (4.1 vs. 14.0%; P=0.07), epistaxis (2.0 vs. 10.5%; P=0.08) and gingival bleeding (4.1 vs. 19.3%; P=0.02) events compared with the peripheral thrombolysis group. Further analyses demonstrated that systolic [odds ratio (OR)=1.10; 95% confidence interval (CI), 1.03-1.17; P<0.01] and diastolic (OR=1.08; 95% CI, 1.02-1.14; P<0.05) blood pressure were protective factors, whereas thrombus age (OR=0.91; 95% CI, 0.84-0.99; P<0.05) was a risk factor for thrombolysis success among patients who underwent local thrombolytic therapy. Overall, the results suggest that local venous infusion of urokinase is superior to peripheral venous infusion for the treatment of patients with thrombosed fistulas.
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http://dx.doi.org/10.3892/etm.2019.7415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447926PMC
May 2019

SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA damage repair.

Sci Adv 2019 03 27;5(3):eaav1118. Epub 2019 Mar 27.

Guangdong Key Laboratory of Genome Instability and Human Disease, Shenzhen University Carson Cancer Center, Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, Shenzhen 518060, China.

The activation of ataxia-telangiectasia mutated (ATM) upon DNA damage involves a cascade of reactions, including acetylation by TIP60 and autophosphorylation. However, how ATM is progressively deactivated after completing DNA damage repair remains obscure. Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. In response to DNA damage, SIRT7 is mobilized onto chromatin and deacetylates ATM during the late stages of DNA damage response, when ATM is being gradually deactivated. Deacetylation of ATM by SIRT7 is prerequisite for its dephosphorylation by its phosphatase WIP1. Consequently, depletion of SIRT7 or acetylation-mimic mutation of ATM induces persistent ATM phosphorylation and activation, thus leading to impaired DNA damage repair. Together, our findings reveal a previously unidentified role of SIRT7 in regulating ATM activity and DNA damage repair.
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http://dx.doi.org/10.1126/sciadv.aav1118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436926PMC
March 2019

Climate and soil parameters are more important than denitrifier abundances in controlling potential denitrification rates in Chinese grassland soils.

Sci Total Environ 2019 Jun 8;669:62-69. Epub 2019 Mar 8.

Key Laboratory of Environmental and Applied Microbiology, CAS, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China. Electronic address:

Denitrification is an important process that influences nitrogen (N) loss and the production of greenhouse gas in grassland soils. However, the relative contributions of abiotic and biotic factors to soil denitrification potential at the regional and sub-regional scales in grassland ecosystems remain elusive. In this study, soil samples were collected from 21 sites at three steppes of China, including the Inner Mongolia Plateau (IMP), the Xinjiang Autonomous Region (XAR) and the Tibetan Plateau (TP) grasslands. Results showed that the key factors controlling the denitrification potential were regional and scale-dependent. At the sub-regional scales, soil pH, aridity index (AI) and total organic carbon (TOC) explained the highest variances on denitrification potential in the IMP, XAR and TP steppe, respectively. At the regional scale, the mean annual precipitation (MAP) was the most important environmental driver for the denitrification potential. Partial least squares (PLS) path modeling revealed that the MAP might regulate denitrification potential directly and indirectly by its effects on the plant and soil properties. Overall, these results help to improve our understandings on the prediction of the denitrification potential under global changes and revealed that the denitrification potential at various scales could be regulated by the multiple interactions of abiotic and biotic factors.
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http://dx.doi.org/10.1016/j.scitotenv.2019.03.093DOI Listing
June 2019

Partial aneurysmectomy for treatment of autologous hemodialysis fistula aneurysm is safe and effective.

J Vasc Surg 2019 Aug 6;70(2):547-553. Epub 2019 Mar 6.

Department of Ultrasonography, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Objective: The purpose of this study was to evaluate the outcome and the factors associated with stenosis after treatment using partial aneurysmectomy for aneurysm in autologous arteriovenous fistulas.

Methods: This retrospective cohort study was conducted from July 2007 to June 2016 and included patients with complicated aneurysms in upper extremity autologous arteriovenous fistulas were treated by partial aneurysmectomy. Vascular ultrasound examination was performed every 6 months after the surgery.

Results: Forty-one patients (median age, 37 years; 70.7% males) were included. Of the patients, 95.1% had a radial-cephalic fistula in the forearm and nearly 88% had 1 or 2 aneurysms in arteriovenous fistulas that had been created for 10 to 84 months. Technical success of partial aneurysmectomy was achieved in all patients. The access diameter (44.0 ± 5.1 mm vs 10.4 ± 1.8 mm; P < .01) and brachial artery blood flow (1618.2 ± 277.0 mL/min vs 772.1 ± 127.4 mL/min; P < .01) were significantly decreased after the surgery. The median follow-up time was 27 months (range, 12-43 months). The primary patency rates at 6 and 12 months were 100% and 95%, respectively. Loss of patency was due to stenosis of the remodeled fistulas, which occurred in seven patients (17%). Multivariate COX regression analysis revealed that diabetes (hazard ratio, 114.28; 95% confidence interval, 2.85-4583.94; P = .01) was a risk factor for the impaired primary patency rates. A larger postprocedure residual diameter trended to favor fistula patency (hazard ratio, 0.46; P = .07). Stenosis was successfully treated with percutaneous transluminal angioplasty.

Conclusions: Partial aneurysmectomy is an effective and safe method for treating aneurysm of upper extremity autologous arteriovenous fistulas, leading to good 12-month primary patency and no aneurysm recurrence. Using a larger catheter to size the revised fistula during aneurysmectomy may increase access patency.
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http://dx.doi.org/10.1016/j.jvs.2018.10.119DOI Listing
August 2019

Transcriptome Sequencing Identifies Novel Immune Response Genes Highly Related to the Severity of Human Adenovirus Type 55 Infection.

Front Microbiol 2019 6;10:130. Epub 2019 Feb 6.

Treatment and Research Center for Infectious Diseases, 302 Military Hospital of China, Beijing, China.

Human adenovirus type 55 (HAdV-55) is considered a highly virulent pathogen causing severe and even deadly pneumonia in immunocompetent people. The mechanisms of HAdV-55-induced initiation and progression of severe pneumonia remain ambiguous. In the current study, we endeavored to identify novel immune response genes which are substantially involved in the pathogenesis of severe inflammation in HAdV-55-infected patients. HAdV-55-infected patients with upper respiratory tract symptoms (minor patients) and pneumonia (severe patients) were enrolled. Through transcriptome sequencing and quantitative real-time PCR, the peripheral blood mononuclear cells of the patients were analyzed. We found that the expression of eight genes, including , , , , , , , and , were closely correlated with the severity of HAdV-55 infection. Most of these genes belong to interleukin-1 family or tumor necrosis factor (TNF) superfamily, respectively. The changes in gene expression were confirmed by Western blot assay. Our data will be crucial for deepening the understanding of the pathogenic mechanisms of severe pneumonia in HAdV-55 infection.
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http://dx.doi.org/10.3389/fmicb.2019.00130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372566PMC
February 2019

Comparing the vascular thromboembolic events following arteriovenous fistula in Chinese population with end-stage renal diseases receiving Clopidogrel versus Beraprost sodium therapy: a retrospective cohort study.

BMC Nephrol 2018 12 27;19(1):376. Epub 2018 Dec 27.

Department of Gynaecology and obstetrics, The First Affiliated Hospital of Sun Yat-sen University, Huangpu East Road No. 183, Huangpu District, Guangzhou, 510700, China.

Background: To assess the time to first on-study vascular thromboembolic events (VTEs) of clopidogrel (CL) or beraprost sodium (BPS) in Chinese population with end-stage renal disease (ESRD) treated with arteriovenous fistula (AVF) surgery.

Methods: From Jan 2009 to May 2015, 346 ESRD cases suffering an AVF surgery and undergoing oral administration of 75 mg CL (initial dose of 300 mg), 1 time/day, for 4 weeks or 40 μg BPS, 3 times/day, for 4 weeks were retrospectively assessed. The primary outcome was time to first on-study VTE.

Results: In total, 222 ESRD cases (CL, n = 112; BPS, n = 110) were assessed, with a median follow-up time of 38.1 months (range, 37-40 months). The mean time to first on-study VTE was 1.2 weeks (0.5-2.3) and 1.8 weeks (1.2-3.8) for CL and BPS, respectively (HR 0.27, 95% CI 0.16-1.45; P = 0.00). An increased incidence of VTEs was found during the 1th-month follow-up, with rates of 14.2 and 5.5% for CL and BPS, respectively (P = 0.03). The difference persisted over time, with rates of 24.1 and 11.8% at final follow-up, respectively (P = 0.02).

Conclusion: CL with an increased risk of VTEs tended to have a VTE within the 1st month after cessation compared with BPS.
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http://dx.doi.org/10.1186/s12882-018-1166-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307208PMC
December 2018

Bloodstream infection due to in liver cirrhosis patients: clinical features and outcomes.

Oncotarget 2018 Nov 13;9(87):35780-35789. Epub 2017 Dec 13.

Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China.

Objectives: The study aimed to investigate the clinical characteristics and antibiotic management, as well as independent indicators for survival within 30 days for Escherichia coli bloodstream infection (BSI) in liver cirrhosis.

Results: Hospital-acquired BSI accounted for 60.07%, with prolonged hospital stay ( = 0.000). The prevalence of Extended Spectrum Beta-Lactamases (ESBL) producing bacteria was 48.26%, which correlated with ICU admission ( = 0.015) and high model for end-stage liver disease (MELD) score at onset of BSI ( = 0.035). Moreover, ESBL producing pathogens showed a high resistant to the common antibiotic families and 27.5% pathogens were confirmed as multidrug-resistant (MDR). MDR infection was significantly correlated with ESBL production, ICU admission, inappropriate empiric therapy, resistance to firstly selected antibiotic, and infection duration ( < 0.05 for all). In addition, appropriate empiric therapy within 48 h (HR = 2.581, 95% CI = 1.166-5.715), ICU admission (HR = 4.434, 95% CI = 2.130-8.823), HE (HR = 2.379, 95% CI = 1.115-5.073) and final MELD (HR = 1.074, 95% CI = 1.044-1.106) were independent indicators for 30-day mortality.

Materials And Methods: The clinical data were collected from 288 eligible patients, and compared according to survival status and sites of infection acquisition. Drug resistance was recorded according to ESBL. In addition, cox regression analysis model was applied to evaluate the risk factors for 30-day mortality.

Conclusions: ESBL production can promote resistance to antibiotics in Escherichia coli. Antibiotic regimens, ICU admission, HE and MELD score can help identify the risk individuals who will benefit from the improved therapeutic regimens.
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http://dx.doi.org/10.18632/oncotarget.23200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254670PMC
November 2018
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