Altered lipid metabolites accelerate early dysfunction of T cells in HIV-infected rapid progressors by impairing mitochondrial function.

The complex mechanism of immune-system damage in HIV infection is incompletely understood. HIV-infected "rapid progressors" (RPs) have severe damage to the immune system early in HIV infection, which provides a "magnified" opportunity to study the interaction between HIV and the immune system. In this study, forty-four early HIV-infected patients (documented HIV acquisition within the previous 6 months) were enrolled. By study the plasma of 23 RPs (CD4+ T-cell count < 350 cells/µl within 1 year of infection) and 21 "normal progressors" (NPs; CD4+ T-cell count > 500 cells/µl after 1 year of infection), eleven lipid metabolites were identified that could distinguish most of the RPs from NPs using an unsupervised clustering method. Among them, the long chain fatty acid eicosenoate significantly inhibited the proliferation and secretion of cytokines and induced TIM-3 expression in CD4+ and CD8+ T cells. Eicosenoate also increased levels of reactive oxygen species (ROS) and decreased oxygen consumption rate (OCR) and mitochondrial mass in T cells, indicating impairment in mitochondrial function. In addition, we found that eicosenoate induced p53 expression in T cells, and inhibition of p53 effectively decreased mitochondrial ROS in T cells. More importantly, treatment of T cells with the mitochondrial-targeting antioxidant mito-TEMPO restored eicosenoate-induced T-cell functional impairment. These data suggest that the lipid metabolite eicosenoate inhibits immune T-cell function by increasing mitochondrial ROS by inducing p53 transcription. Our results provide a new mechanism of metabolite regulation of effector T-cell function and provides a potential therapeutic target for restoring T-cell function during HIV infection.

Proximity-induced exponential amplification reaction triggered by proteins and small molecules.

We proposed a method to regulate nucleic acid polymerization by proximity and designed an ultrasensitive biosensor based on proximity-induced exponential amplification reaction for proximity assay of proteins (streptavidin) and small molecules (adenosine triphosphate), which allows us to detect a variety of interesting targets by simply changing the binding sites of DNA.

Reporting quality of systematic reviews with moxibustion.

BACKGROUND: Moxibustion is one of the major interventions of Chinese medicine (CM). The systematic reviews (SRs) are essential references for evaluating the efficacy and safety of moxibustion interventions. This study aimed to assess the reporting quality of these SRs, particularly whether necessary information related to moxibustion was adequately reported. METHODS: Seven databases (including four English and three Chinese databases) were systematically searched for SRs of moxibustion that were published up to 31 December 2019. The primary analysis was to assess their reporting quality based on 27-item of the Preferred Reporting Items for SRs and Meta-Analyses (PRISMA) and 14-item of moxibustion-related information designed according to CM theory and the STandards for Reporting Interventions in Clinical Trials Of Moxibustion (STRICTOM). Descriptive statistics were also used to analyze their baseline characteristics. RESULTS: A total of 97 SRs of moxibustion were identified from 2011 to 2019. For 27-item of PRISMA, except item 5, 8, 16 and 23, the remaining 23 items had the reporting compliances higher than 55%, of which 2 items (item 20 and 26) were fully reporting (100%). However, for moxibustion-related information, 69.1% (67/97) SRs did not provide the specific type of moxibustion, 39.2% (38/97) lacked details regarding the materials, procedure and technique used for moxibustion, 67.0% (65/97) did not report the selection criteria of acupoints for moxibustion, 28.9% (28/97) did not provide the number or duration of treatment sessions, 69.1% (67/97) did not provide any information about safety evaluation, and 94.8% (92/97) SRs did not report the treatment environment. For 51 (55.4%) of 92 SRs that included meta-analysis, it was impossible to assess whether meta-analysis had been properly conducted due to inadequate reporting of moxibustion interventions. CONCLUSION: The reporting quality of SRs of moxibustion need further improvements in terms of adequate reporting of moxibustion interventions and of moxibustion-related rationales. Reporting guideline of "PRISMA extension for moxibustion interventions" should be developed thus to improve their quality.

PRISMA extension for moxibustion 2020: recommendations, explanation, and elaboration.

BACKGROUND: Moxibustion is a common intervention of Chinese medicine (CM). Systematic reviews (SRs) on moxibustion are increasing. Although the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement provides guidelines for SRs, the quality of moxibustion-related SRs is still not satisfactory. In particular, descriptions of the interventions and the rationale for using moxibustion are insufficient. To address these inadequacies, the working group developed this PRISMA extension for reporting SRs of moxibustion (PRISMA-M 2020). METHODS: A group of CM clinical professionals, methodologists of SRs, reporting guideline developers, and journal editors developed this PRISMA-M 2020 through a comprehensive process that includes registration, literature review, consensus meetings, Delphi exercises for soliciting comments, and revision, resulting in this final draft. RESULTS: Seven of the 27 PRISMA checklist items, namely title (1), rationale (3), eligibility criteria (6), data item (11), additional analyses (16), study characteristics (18), and additional analysis (23), were extended, with specific reference to the application of moxibustion. Illustrative examples and explanations for each item are provided. CONCLUSION: The PRISMA-M 2020 will help improve the reporting quality of SRs with moxibustion. SYSTEMATIC REVIEW REGISTRATION: We have registered it on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network, particularly under the item of PRISMA-TCM: http://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-systematic-reviews/#65 .

Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection.

BACKGROUND: Disease progression in the absence of therapy varies significantly in mono-HIV and HCV infected individuals. Virus-specific CD8+ T cells play an important role in restricting lentiviral replication and determining the rate of disease progression during HIV and HCV mono- and co-infection. Thus, understanding the similarities in the characteristics of CD8+ T cells in mono-HIV and HCV infection at the transcriptomic level contributes to the development of antiviral therapy. In this study, a meta-analysis of CD8+ T cell gene expression profiles derived from mono-HIV and HCV infected individuals at different stages of disease progression, was conducted to understand the common changes experienced by CD8+ T cells. METHODS: Five microarray datasets, reporting CD8+ T cell mRNA expression of the mono-HIV and HCV infected patients, were retrieved from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified via integrative meta-analysis of expression data (INMEX) program. Network analysis methods were used to assess protein-protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs. MirDIP and miRDB online prediction tools were used to predict potential microRNAs (miRNAs) targeting hub genes. RESULTS: First, we identified 625 and 154 DEGs in the CD8+ T cells originating from mono-HIV and HCV chronic progressor patients, respectively, compared to healthy individuals. Among them, interferon-stimulated genes (ISGs) including ISG15, IFIT3, ILI44L, CXCL8, FPR1 and TLR2, were upregulated after mono-HIV and HCV infection. Pathway enrichment analysis of DEGs showed that the "cytokine-cytokine receptor interaction" and "NF-kappa B" signaling pathways were upregulated after mono-HIV and HCV infection. In addition, we identified 92 and 50 DEGs in the CD8+ T cells of HIV non-progressor and HCV resolver patients, respectively, compared with corresponding chronic progressors. We observed attenuated mitosis and reduced ISG expression in HIV non-progressors and HCV resolvers compared with the corresponding chronic progressors. Finally, we identified miRNA-143-3p, predicted to target both IFIT3 in HIV and STAT5A in HCV infection. CONCLUSIONS: We identified DEGs and transcriptional patterns in mono-HIV and HCV infected individuals at different stages of disease progression and identified miRNA-143-3p with potential to intervene disease progression, which provides a new strategy for developing targeted therapies.

Reporting quality of Cochrane systematic reviews with Chinese herbal medicines.

BACKGROUND: Chinese herbal medicines (CHMs) are the major interventions of traditional Chinese medicine (TCM), which are typically administered as either single herbs or formulas. The Cochrane systematic reviews (SRs) of CHMs are essential references for evaluating the efficacy and safety of CHMs interventions; they are expected to be accurate and reliable. This study aimed to assess the reporting quality of these SRs, particularly whether necessary information related to CHM was adequately reported. METHODS: The Cochrane Database was systematically searched for all SRs of CHM that were published up to 31 December 2017. The primary analysis was to assess their reporting quality based on 27-item of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and 9-item of CHM-related information designed according to TCM theory. Descriptive statistics were additionally used to analyze their baseline characteristics. RESULTS: A total of 109 Cochrane SRs of CHM were identified from 1999 to 2017. For 27-item of PRISMA, 26 had the reporting compliances higher than 50%, of which 11 were fully reporting (100%). However, for CHM-related information, 65 (59.6%) SRs did not report the specific name of the CHM in the title, 42 (38.5%) lacked TCM-related rationales in the introduction, 62 (56.9%) did not include CHM-related characteristics in the additional analyses, and 77 (70.6%) did not analyze CHM results in terms of TCM-related theories in the discussion. Of 97 SRs that included clinical trials, 38 (39.2%) did not provide the details of composition and dosage of CHMs, 85 (87.6%) did not report the CHM sources, 13 (13.4%) did not provide the dosage form, 95 (97.9%) lacked CHM quality control information, and 57 (58.8%) did not describe details of the controls. For 62 (72.9%) of 85 SRs that included meta-analysis, it was impossible to assess whether meta-analysis had been properly conducted due to inadequate reporting of CHM interventions. CONCLUSION: Although the Cochrane SRs of CHM showed reporting compliance with PRISMA checklist, their reporting quality needs improvement, especially about full reporting of CHM interventions and of TCM-related rationales. Reporting guideline of "PRISMA extension for CHM interventions" should be developed thus to improve their quality.

Thrombus aspiration catheter improve the myocardial reperfusion of STEMI patients with high thrombus load during the emergency PCI operation.

OBJECTIVE: This study aims to discuss the efficacy and safety of the application of thrombus aspiration catheters during emergency PCI operations for acute ST-elevation myocardial infarction (STEMI) patients with high thrombus load. METHODS: A total of 204 patients diagnosed with acute STEMI and high thrombus load in the Sixth Affiliated Hospital of Guangxi Medical University from July 1, 2016 to June 30, 2017 were selected for the present study. These patients were randomly divided into two groups: thrombus catheter aspiration group (group A, n = 101), and balloon dilatation group (group B, n = 103). The blood flow of the culprit coronary artery in the thrombolysis in myocardial infarction (TIMI) immediately after the emergency PCI operation in these two groups of patients was recorded. Then, an echocardiogram was performed to determine the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) after the operation, and data on major adverse cardiovascular events (MACE) during the 30 days of postoperative follow-up were collected. RESULTS: The comparative difference between these two groups of patients in terms of hypertension, smoking, diabetes, usage rate of GPIIb/IIIa receptor antagonist, time from hospitalization to balloon dilatation (D2B) and other basic clinical data was not statistically significant (P > 0.05). The postoperative TIMI flow grade of these two groups of patients improved, and the comparative difference between the data obtained from these two groups was statistically significant (P < 0.05). The comparative difference between these two groups in terms of LVEDD and LVEF at 7 days after the operation was not statistically significant (P > 0.05). There was a difference in the occurrence rate of MACE in these two groups of patients during the 30 days of postoperative follow-up, but the comparative difference between these two groups was not statistically significant (P = 0.335). CONCLUSION: The application of thrombus aspiration catheter during the emergency PCI operation of STEMI patients with high thrombus load can better improve the myocardial reperfusion. There is no basis for increasing the stroke occurrence risk. However, it obviously fails to improve the recent prognosis and more studies need to explore its effect on myocardial remodeling and major adverse cardiovascular events.

Value of the expression of miR-208, miR-494, miR-499 and miR-1303 in early diagnosis of acute myocardial infarction.

AIMS: This study aims to investigate the value of the expression of miR-208, miR-494, miR-499 and miR-1303 in the early diagnosis of acute myocardial infarction (AMI). MAIN METHODS: Patients were divided into two groups: AMI group (n = 41), and Stable angina pectoris (SAP) group (n = 32). Peripheral venous blood was sampled from these patients at the time of admission (T0), 6 h after onset (T6) and 12 h after onset (T12), while blood was sampled once from healthy subjects who underwent physical examination in the same time period (control group, n = 10). The expression of miR-208, miR-494, miR-499 and miR-1303 in serum were detected by real-time quantitative polymerase chain reaction (qRT-PCR), and differences in miRNA expression among these three groups of patients were analyzed. KEY FINDINGS: Serum miR-208, miR-494, miR-499 and miR-1303 expression levels at different time points were significantly higher in the AMI group than in the SAP group and control group. The differences among these groups were statistically significant (P < 0.05), while the difference between the SAP group and control group was not statistically significant (P > 0.05). Variation trend: The miRNA levels above began to increase at T0 in the AMI group, the peak levels of miR-208, miR-494 and miR-499 appeared before T12, and the peak level of miR-1303 appeared between T6 and T12, or after T12. SIGNIFICANCE: miR-208, miR-494, miR-499 and miR-1303 were not superior to hs-cTnI as myocardial markers in the diagnosis of early acute myocardial infarction.

Laparoscopic radical cystectomy with orthotopic ileal neobladder: report of 33 cases.

BACKGROUND: The laparoscopic radical cystectomy (LRC) with orthotopic ileal neobladder is now applied to treat invasive bladder cancer, however, it has not been well codified and illustrated. We describe in this paper a technique step by step that we have developed in 33 patients and achieved excellent results. METHODS: The surgical procedure can be divided into eight steps: laparoscopic pelvic lymphadenectomy and mobilization of the distal ureters; exposing Denonvillier's space and the posterior aspect of prostate; exposing retropubic space and anterior surface of the bladder; dividing the lateral pedicles of the bladder and the prostate; dividing the apex of the prostate; extracorporeal formation of the ileal pouch; extracorporeal implantation of the ureters; and laparoscopic urethra-neobladder anastomosis. This operation was performed in 33 patients, 29 males and 4 females, with muscle invasive bladder cancer between December 2002 and September 2004. RESULTS: The operating time was 5.5-8.5 hours with an average of 6.5 hours; the estimated blood loss was 200-1000 ml with an average of 460 ml. The surgical margins of the bladder specimen were negative in all patients. There was no evidence of local recurrence at follow-up of 1-21 months in all the patients. However lymph node metastases were found in one case at 9 months postoperatively. Most of patients achieved urine control 1 to 3 months after surgery. The daytime continence rate was 94% (31 cases) and nighttime continence rate was 88% (29 cases). Urodynamic evaluation was performed between 3 and 6 months postoperatively for all cases. The mean value of neobladder capacity was (296 +/- 37) ml. The mean value of maximum flow rate was (18.7 +/- 7.1) ml/s. The mean residual urine volume was (32 +/- 19) ml. In all cases, excretory urography at 1 to 2 months postoperatively demonstrated slightly dilated upper urinary tracts without ureteral obstruction, which resolved at follow up. Cystography showed neobladders being similar in shapes to normal. Two small ureteral nipples with intermittently efflux of urine were observed at cystoscopy in most patients. Postoperative complications occurred in 6 of 33 patients (18%), including pouch leakage in 2 cases, pelvic infection in 1, partial small bowel obstruction in 2 and neobladder-vaginal fistula in 1. CONCLUSIONS: The LRC with orthotopic ileal neobladder is a feasible option for bladder cancer when radical cystectomy is indicated. The extracorporeal formation of the ileal pouch and ureteral implantation through a small lower midline incision can simplify the complexity of the procedures, shorten the duration of surgery and reduce the medical expenses.

[Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression in superficial transitional cell bladder carcinoma].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) can promote the proliferation of endothelial cell and angiogenesis. They are important materials in growth, invasion, and metastasis of tumor. There were few reports of their difference in single and multiple superficial transitional cell bladder carcinoma. Our objective was to study the expression of them in single and multiple superficial transitional cell bladder carcinoma and their clinical significance. METHODS: Immunohistochemical method was used to study the VEGF and bFGF expression in 60 cases of superficial transitional cell bladder carcinoma and in 10 cases of normal bladder tissue (as control). RESULTS: The expression levels of VEGF (55.6%), bFGF (50.0%), and coexpression level of VEGF and bFGF (50.0%) in the multiple superficial transitional cell bladder carcinoma were higher than that in single tumor. The recurrent rate in the patients with VEGF high expression (61.1%) was higher than that in the patients with VEGF low expression (16.7%). CONCLUSION: The expression levels of VEGF and bFGF were correlated with the biological behavior of superficial transitional cell bladder carcinoma.