Therapeutic effect of folic acid combined with decitabine on diabetic mice.

AIM: To evaluate the therapeutic effect of folic acid combined with decitabine on diabetic mice. METHODS: The diabetic model of db/db mice were randomly divided into model group, folic acid group, decitabine group, folic acid combined with decitabine group, and C57 mice as normal control group. The density of retinal blood vessels and retinal thickness were detected by fundus photography and optical coherence tomography, respectively. Pathological changes of retina were observed by hematoxylin-eosin (HE) staining. The homocysteine (Hcy) in serum was detected by enzyme linked immunosorbent assay (ELISA). TdT-mediated dUTP nick-end labeling (TUNEL) was used to detect apoptosis in retinal tissue. Evans blue dye was used to detect the permeability of retinal blood vessels. The platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor receptor (VEGFR) protein were detected by Western blot. The 3-nitrotyrosine (3-NT) and 4-hydroxynonanine (4-HNE) were detected by immunohistochemistry. RESULTS: The density of retinal blood vessels, retinal thickness, retinal vascular permeability and the proportion of apoptotic cells of retinal tissue in the model group increased significantly than control group (P<0.05). The Hcy in serum and the levels of CD31, VEGFR, 3-NT, and 4-HNE in retinal tissue increased significantly in the model group (P<0.01). Folic acid and decitabine both reversed these changes significantly, and the combination of the folic acid and decitabine worked best. CONCLUSION: The combination of folic acid and decitabine has a more significant protective effect on the retina in diabetic mice.

The heterophilicic epitopes in conserved HA regions of human and avian influenza viruses can produce antibodies that bound to kidney tissue.

Influenza virus infection can cause kidney damage. However, the link between influenza infection and disease is still unclear. The purpose of this study was to analyze the relationship between heterophilic epitopes on H5N1 hemagglutinin (HA) and disease. The monoclonal antibody (mAb) against H5N1 was prepared, mAbs binding to human kidney tissue were screened, and the reactivities of mAbs with five different subtypes of influenza virus were detected. Design and synthesize the peptides according to the common amino acid sequence of these antigens, and analyze the distribution of the epitope on the crystal structure of HA. Immunological methods were used to detect whether the heterophilic epitopes could induce the production of antibodies that cross-react with kidney tissue. The results showed that H5-30 mA b binding to human kidney tissue recognized the heterophilic epitope 191-LVLWGIHHP-199 on the head of HA. The key amino acid were V192, L193, W194 and I196, which were highly conserved in human and avian influenza virus HA. The heterophilic epitope could induce mice to produce different mAbs binding to kidney tissue. Such heterophilic antibodies were also detected in the serum of the patients. It can provide materials for the mechanism of renal diseases caused by influenza virus infection.

Identification of Heterophilic Epitopes of H1N1 Influenza Virus Hemagglutinin.

Our previous studies found that the H1-50 monoclonal antibody (mAb) of influenza A virus hemagglutinin (HA) cross-reacted with pancreatic tissue and islet ß-cells, and further studies showed that H1-50 mAb binds to prohibitin (PHB) protein of islet ß-cells. These suggest that there are heterophilic epitopes between influenza virus HA and pancreatic tissue, which may be involved in the pathogenesis of type 1 diabetes. To further investigate these heterophilic epitopes, we screened binding epitopes of H1-50 mAb using a phage 12-peptide library. DNA sequencing and comparative analysis were performed on specific positive phage clones, and the sequence of 12-peptide binding to H1-50 mAb was obtained. The binding epitopes of H1-50 mAb in influenza virus HA were determined by sequence analysis and experimental verification, and their distribution within the three-dimensional structure was assessed by PyMOL. The results showed that H1-50 mAb specifically binds to polypeptides (306-SLPFQNIHPITIGK-319) of influenza A virus HA, located in the stem of the HA protein. However, there is no specific binding sequence between H1-50 mAb and the PHB protein of islet ß-cells in the primary structure, and we speculate that the binding of H1-50 mAb to islet ß-cells may depend on the spatial conformation. The identification of the heterophilic epitopes of H1N1 influenza virus hemagglutinin provides a new perspective on type 1 diabetes that may be caused by influenza virus infection, which may contribute to the prevention and control of influenza.

A new prognostic model for predicting outcomes of patients with recurrent or metastatic nasopharyngeal carcinoma receiving subsequent line (≥2 lines) anti-programmed death-1 monotherapy.

OBJECTIVES: About 17.7-34.0 % of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) responded well to anti-PD-1 monotherapy. We sought to establish a nomogram to estimate the progression-free survival (PFS) of RM-NPC patients receiving subsequent-line anti-PD-1 monotherapy. MATERIALS AND METHODS: This cohort study investigated consecutive RM-NPC patients undergoing anti-PD-1 monotherapy. A nomogram was developed in the training cohort (n = 161), using a Cox multivariate model with backward stepwise inclusion, and was validated in the validation cohort (n = 69). Its predictive accuracy was assessed using a concordance index (C-index) and calibration curve. The primary endpoint was PFS. Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: Liver metastasis, albumin, lactate dehydrogenase, monocyte-to-lymphocyte ratio, and plasma Epstein-Barr virus DNA were used to develop a nomogram that could separate patients into favourable- and unfavourable-prognosis groups. The C-index in the training and validation cohort were 0.70 and 0.68, respectively, which was confirmed by calibration curves. Median PFS (mPFS) was lower for the unfavourable-prognosis than for the favourable-prognosis group (1.80 vs 4.93; hazard ratio 2.49 [95 % confidence interval: 1.78-3.49]; p < 0.001), across all subgroups. OS exhibited the same pattern. The ORR and DCR were markedly lower in the unfavourable-prognosis than in the favourable-prognosis group. All results were confirmed in the validation cohort. CONCLUSION: Our model is a reliable prognostic indicator of PFS in RM-NPC patients undergoing anti-PD-1 monotherapy, allowing robust estimation of the immunotherapy benefit an individual might derive.

Sex-related differences in clinical outcomes and predictive factors in the very elderly patients with ACS undergoing PCI.

Background: As shown in previous studies, there may be sex-related differences in clinical outcomes in patients with acute coronary syndromes (ACS) after percutaneous coronary intervention (PCI). However, the benefits of PCI in very elderly ACS patients and the gender differences were poorly described and understood. We investigated the clinical characteristics and outcomes after PCI by sex stratification, and the predictive factors of major adverse cardiovascular and cerebrovascular events (MACCE) in this very elderly ACS cohort. Methods: A total of 1,676 consecutive ACS patients (50.2% women) aged ≥80 years old between January 2013 and May 2020 were recruited in this study. All patients were divided into four groups according to gender and treatment: male PCI (n = 321) and conservative management groups (n = 513), and female PCI (n = 283) and conservative management groups (n = 559). Clinical and coronary lesion characteristics were compared among four groups, also the clinical outcomes. MACCE and their predictive factors were assessed using Kaplan-Meier curve and Cox regression analysis. Results: PCI procedures were conducted in 604 patients, and 1,072 were conservative management. Men were most likely to present with prior myocardial infarction (MI), peripheral artery disease, and chronic total occlusion (CTO); women had a higher prevalence of hypertension and dyslipidemia. The proportion of men receiving PCI procedures was significantly higher than that of women (38.5 vs. 33.6%, p = 0.038). Compared to conservative management, successful PCI significantly improved composite MACCE in both men (33.9 vs. 18.4%, p < 0.001) and women (27.9 vs. 20.8%, p = 0.026). There were no differences between sex in the improvement of clinical outcomes after PCI. In addition, age, ST-segment elevation myocardial infarction (STEMI), log N-terminal pro-brain natriuretic peptide (NT-proBNP), P2Y12 receptor antagonist, and ß-blocker were independently associated with the incidence of MACCE after PCI tested by the Cox regression model, but not gender (male: hazard ratio (HR) 1.275, 95% confidence interval (CI) 0.853-1.905, p = 0.236). Conclusion: In this very elderly ACS cohort, men presented with more complex clinical conditions, and women were less likely to receive PCI treatment. Both women and men had similar benefits from the PCI procedure in the decrease of MACCE.

First-Line Immunochemotherapy Versus Palliative Chemotherapy Plus Definitive Radiation Therapy for de novo Metastatic Nasopharyngeal Carcinoma: A Matched Cohort Study.

BACKGROUND: The combined use of immune checkpoint inhibitors (ICIs) with palliative chemotherapy (PCT) is a promising first-line treatment for de novo metastatic nasopharyngeal carcinoma (mNPC). However, the efficacy of ICIs with PCT vs PCT with definitive radiation therapy (DRT) remain unclear. METHODS: Patients with mNPC who received first-line immunochemotherapy (ICI + PCT) or PCT + DRT were included. Propensity score matching (PSM) was applied to balance potential confounders between patients who did and did not undergo DRT (at a ratio of 1:1). Progression free survival (PFS) and overall survival (OS) were compared between the 2 groups using a log-rank test and Cox proportional hazard model. RESULTS: Among all participants, 149 received ICI + PCT. After PSM, 149 patients were included in the PCT + DRT group. First-line immunochemotherapy was associated with significantly improved PFS (median 9.0 months vs 12.0 months, P < .001) and OS (median 12.5 months vs 19.9 months, P < .001). Subgroup analysis revealed that tumor response to immunochemotherapy, metastatic organs, and number of metastatic sites potentially affected the efficacy of DRT after first-line immunochemotherapy. CONCLUSION: Compared with PCT + DRT, first-line immunochemotherapy was associated with improved PFS and OS in patients with mNPC but not in patients with unfavorable tumor response and metastasis involving the liver, distant nodes, or multiple sites.

Identification and analysis of B cell epitopes of hemagglutinin of H1N1 influenza virus.

The frequent variation of influenza virus hemagglutinin (HA) antigen is the main cause of influenza pandemic. Therefore, the study of B cell epitopes of HA is of great significance in the prevention and control of influenza virus. In this study, the split vaccine of 2009 H1N1 influenza virus was used as immunogen, and the monoclonal antibodies (mAbs) were prepared by conventional hybridoma fusion and screening techniques. The characteristics of mAbs were identified by ELISA method, Western-blot test and hemagglutination inhibition test (HI). Using the obtained mAbs as a tool, the B cell epitopes of HA were predicted by ELISA blocking test, sandwich ELISA method and computer simulation method. Finally, four mAbs against HA antigen of H1N1 influenza virus were obtained. The results of ELISA and computer prediction showed that there were at least two types of epitopes on HA of influenza virus. The results of this study complemented the existing methods for predicting HA epitopes, and also provided a new method for predicting other pathogenic microorganisms.

[Effects of Astragalus polysaccharide on imiquimod-induced psoriasiform dermatitis in mice and its mechanisms].

Objective: To investigate the effects and mechanisms of Astragalus polysaccharide on improving imiquimod-induced psoriasiform dermatitis in mice. Methods: Forty healthy female C57BL/6 mice were randomly divided into 5 groups, including blank control group, model group, astragalus polysaccharide high-dose group (200 mg/kg), medium-dose group (100 mg/kg) and low-dose group (50 mg/kg), with 8 mice in each group. The mice in model group and astragalus polysaccharide treatment group were treated with 5% imiquimod cream on the back to induce psoriasiform dermatitis. PASI score was monitored, and the secretion of inflammatory factors was determined by ELISA. The secretion of inflammatory factors was closely related to the infiltration of macrophages. The infiltration of macrophages in skin was detected by flow cytometry to further explore the effect of different concentrations of APS on psoriasis. Results: Compared with control group, the PASI score and the serum levels of TNF-α, IL-1ß and IL-6 were increased significantly (P＜0.05), and the infiltration of macrophages in skin tissue was increased significantly in model group (P＜0.05). Compared with model group, the PASI score was decreased significantly (P＜0.05), and the serum levels of TNF-α, IL-1ß and IL-6 were down-regulated significantly in astragalus polysaccharide high-dose and medium-dose groups (P＜0.05). The infiltrating macrophages in skin tissue were decreased significantly in Astragalus polysaccharide high-dose group (P＜0.05). Conclusion: Astragalus polysaccharide improve psoriasiform dermatitis in mice by inhibiting the infiltration of macrophages in skin tissue and decreasing the secretion of TNF-α, IL-1ß and IL-6 in serum.

Multi-Concept Frailty Predicts the Late-Life Occurrence of Cognitive Decline or Dementia: An Updated Systematic Review and Meta-Analysis of Longitudinal Studies.

Background: Frailty is a multidimensional syndrome that increases an individual's vulnerability for developing adverse health outcomes, which include dementia. It might serve as a promising target for dementia prevention. However, there are currently no studies summarizing the association between multi-concept frailty and the risk of cognitive disorders. This study aims to summarize the evidence of associations between multi-concept frailty and cognitive disorders based on longitudinal studies. Methods: Scopus, The Cochrane Library, PsycINFO, CINAHL, PubMed, and EMBASE databases were searched from inception to January 2, 2022. Longitudinal studies, which explored the association of frailty with incident risk of cognitive decline or dementia, were included. The multivariable-adjusted effect estimates were pooled by random-effects models. The evidence credibility was depicted according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Results: A total of 30 longitudinal studies were included. Four types of frailty concepts were involved, including physical, cognitive, social, and biopsychosocial frailty. The meta-analysis comprised 20 studies of 252,571 older adults (mean age: 64.1-80.4 years), among whom 7,388 participants developed cognitive decline or dementia. Physical frailty was associated with higher risk of developing cognitive disorders [pooled relative risk (pRR) = 1.52, 95% confidence interval (CI): 1.28-1.80, I 2 = 21.2%, pRR = 1.62 for cognitive decline, 95% CI: 1.07-2.45, I 2 = 40.2%, pRR = 1.37 for all-cause dementia (ACD), 95% CI: 1.13-1.66, I 2 = 0.0%]. Cognitive frailty (pRR = 2.90, 95% CI: 1.28-6.55, I 2 = 78.1%) and pre-frailty (pRR = 4.24, 95% CI: 2.74-6.56, I 2 = 30.2%) were linked to higher risk of ACD. Biopsychosocial frailty could predict a 41% (pRR = 1.41, 95% CI: 1.17-1.71) elevated risk of cognitive decline or dementia [pRR = 1.53 (95% CI: 1.19-1.96) for ACD and 1.11 (95% CI: 1.05-1.17) for Alzheimer's disease (AD)]. In the systematic review, social frailty was associated with a 53% higher risk of AD. Preventing frailty could avoid a maximum of 9.9% cognitive disorders globally. The overall evidence strength is rated as low-to-moderate. Inconsistency and imprecision are major sources of bias. Conclusion: Frailty in late life is a promising risk factor for cognitive disorders. Frail elderly should be monitored for their cognitive dynamics and initiate early prevention of dementia. Systematic Review Registration: www.ClinicalTrials.gov, identifier CRD4202127 3434.

Deintensified Chemoradiotherapy for Pretreatment Epstein-Barr Virus DNA-Selected Low-Risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Randomized Noninferiority Trial.

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

Prognostic Value of NT-proBNP in Patients With Successful PCI for ACS and Normal Left Ventricular Ejection Fraction.

BACKGROUND: Patients undergoing successful percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) with normal left ventricular ejection fraction (LVEF) are generally considered to have successful clinical outcomes; however, there are still significant differences in clinical outcomes among these patients. The aim of the study was to find a common indicator to predict the risk of major adverse cardiac and cerebrovascular events (MACCE) in this population. METHODS: A total of 3986 patients with ACS were divided into 4 groups based on the quartile (Q) values of peak N-Terminal pro-brain natriuretic peptide (NT-proBNP) measured during hospitalization. The incidence of MACCE was compared among Q1-Q4 groups during follow up. Multivariate Cox regression analysis was performed to identify independent prognostic factors of MACCE. Receiver operating characteristic (ROC) curve was generated to compare the area under the curve (AUC) for MACCE by adding NT-proBNP to the Thrombolysis in Myocardial Infarction (TIMI) risk score. RESULTS: NT-proBNP was significantly positively correlated with peak values of cardiac troponin I (cTnI) (r = 0.418), high-sensitivity C-reactive protein (hs-CRP) (r = 0.397) and left ventricular end-diastolic diameter (LVEDD) (r = 0.075) (P < 0.001). The risks of composite MACCE (5.6%, 9.1%, 13.0%, 20.1%, P < 0.001), all-cause death (1.0%, 2.5%, 4.1%, 8.4%, P < 0.001) and non-fatal myocardial infarction (2.0%, 3.4%, 4.8%, 6.2%, P < 0.001) were significantly higher in the higher Q groups. In multivariate analysis, the Q4 group displayed an independent 2.2-fold increase for MACCE compared to Q1 (HR: 2.16; 95%CI: 1.57-2.99; P < 0.001). Compared with TIMI risk score alone, TIMI+NT-proBNP showed improved AUCs: cardiovascular death (P = 0.0008), and heart failure requiring hospitalization (P = 0.0017). CONCLUSIONS: In patients with ACS with successful PCI and normal LVEF, elevated NT-proBNP was significantly associated with poor clinical outcomes. These results suggest that NT-proBNP is a useful biomarker for prognosis and risk stratification in this population.

Monoclonal Antibody Targeting the HA191/199 Region of H1N1 Influenza Virus Mediates the Damage of Neural Cells.

Vaccination is the most effective mean of preventing influenza virus infections. However, vaccination-induced adverse reactions of the nervous system, the causes of which are unknown, lead to concerns on the safety of influenza A vaccine. In this study, we used flow cytometry, cell ELISA, and immunofluorescence to find that H1-84 monoclonal antibody (mAb) against the191/199 region of the H1N1 influenza virus hemagglutinin (HA) protein binds to neural cells and mediates cell damage. Using molecular simulation software, such as PyMOL and PDB viewer, we demonstrated that the HA191/199 region maintains the overall structure of the HA head. Since the HA191/199 region cannot be removed from the HA structure, it has to be altered via introducing point mutations by site-directed mutagenesis. This will provide an innovative theoretical support for the subsequent modification the influenza A vaccine for increasing its safety.

[Evidence of clinical randomized controlled trial study in treatment of acute cerebral infarction with traditional Chinese medicine in recent five years].

To systematically search and sort out the clinical randomized controlled trial(RCT) on the prevention and treatment of acute cerebral infarction with traditional Chinese medicine(TCM) by using the method of evidence map, and to understand the evidence distribution of related studies. CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Cochrane Library and Web of Science were retrieved from January 2016 to September 2020, and literatures related to the prevention and treatment of acute cerebral infarction with traditional Chinese medicine were included. Text description combined with table and bubble chart were used to analyze the distribution characteristics of evidence. A total of 1 102 clinical articles in recent five years were retrieved. The annual trend of clinical study publication, study size, TCM therapy category and main scheme, and study literature quality were analyzed. We find that TCM treatment of acute cerebral infarction has become a hot topic of clinical research, the number of literature showed a trend of increased year by year, various means of intervention of TCM in the treatment of the advantages of increasingly highlight. Follow-up clinical research should highlight the characteristics of TCM: in the analysis of outcome indicators; increase the neuropsychological patients after stroke and cognitive ability, and the theory of combined treatment of TCM disease when thoughts; At the same time, the quality of clinical research needs to be improved. At present, there is still a lack of unified standards for the production of evidence map. This study is the first to explore the application of evidence map to summarize and display the clinical research status of TCM treatment of acute cerebral infarction, and combine it with the setting of priority areas of TCM clinical research, so as to provide a reference basis for determining the priority topic selection of TCM treatment optimization research.

[Analysis of status quo of outcome indicators of randomized controlled trials in treatment of acute ischemic stroke with acupuncture in recent three years].

To analyze the use of outcome indicators of randomized controlled trial(RCT) of acupuncture in the treatment of acute ischemic stroke in recent three years, so as to provide a basis for building a study on the core outcome indicators for the treatment of acute ischemic stroke with acupuncture. The RCTs of acupuncture treatment for acute ischemic stroke in recent three years were collec-ted through computer retrieval of eight Chinese and English databases and two clinical trial registries at home and abroad. Literature was screened out, and data was extracted. Risk of assessment bias tool Cochrane 6.1 was used for bias risk assessment, outcome indicators were summarized and analyzed. A total of 47 RCTs were included, and 3 studies were trials registration scheme. Outcome indicators were divided into 6 categories according to functional attributes, namely physical symptoms/signs, physical and chemical examination, quality of life, traditional Chinese medicine symptoms/syndromes, safety events and long-term prognosis. The study found that in addition to the common problems in previous studies covered by the status quo of outcome indicators selection of RCT of acupuncture in the treatment of acute ischemic stroke, there were also the other problems as follows: emphasis on macroscopic efficacy indicators but neglect of acupuncture specific indicators, lack of characteristic indicators and economic indicators of traditional Chinese medicine therapy, and unification of indicators measurement tool and measurement time point. In the future, the outcome indicators set for the treatment of acute ischemic stroke with acupuncture shall be established, and the core outcome indicators set shall be in line with the characteristics of traditional Chinese medicine treatment.

[Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of cerebral ischaemic stroke].

There have been many clinical trials, systematic reviews/Meta-analysis proving that Xingnaojing Injection has a good clinical efficacy in treatment of cerebral ischaemic stroke, but with fewer comprehensive descriptions. In this study, an overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treating cerebral ischaemic stroke was performed to provide current situation of evidences and basis for clinical practice. CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science were retrieved through computers. A total of 6 literatures were included in this study. By AMSTAR-2 checklist and GRADE, the quality of included systematic reviews and the efficacy of Xingnaojing Injection were evaluated. The results of AMSTAR-2 checklist showed an extremely low quality for all of the 6 systematic reviews. According to the results of GRADE evaluation, among 55 outcomes, there were 2 outcomes with a medium quality, 4 outcomes with a low quality and 49 outcomes with an extremely low quality. The 6 systematic reviews reached a consistent conclusion that Xingnaojing Injection was effective in the treatment of cerebral ischaemic stroke. This therapy could improve the total efficacy, neurological deficit scores, hemodynamic and hemodynamic parameters. However, the methodolo-gical quality of all literatures was extremely low. The evidence levels of outcomes were between extremely low to medium. The effectiveness of Xingnaojing Injection in the treatment of cerebral ischaemic stroke still needs to be further verified by more high-quality studies. In the future, relevant clinical studies and systematic reviews/Meta-analysis shall be carried out in a strict accordance with relevant regulations.

[Overview of systematic reviews of Panax notoginseng saponins in treatment of acute cerebral infarction].

To overview the systematic reviews of Panax notoginseng saponins in the treatment of acute cerebral infarction. CNKI, CBM, Wanfang, VIP, PubMed, Cochrane Library and EMbase databases were retrieved to collect the systematic reviews of the efficacy of P. notoginseng saponins in the treatment of acute cerebral infarction. The retrieval time was from the time of database establishment to January 2021. After two researchers independently screened out the literature and extracted the data, AMSTAR-2 scale was used to evaluate the methodological quality of the included systematic reviews, GRADE system was used to grade the quality of evidences of the outcome indicators, and the efficacy evaluation was summarized. A total of 5 systematic reviews were included. AMSTAR-2 evaluation results showed that 3 items were relatively complete, while 4 items had a poor overall quality. P. notoginseng saponins combined with conventional Western medicine therapy was superior to single conventional therapy in the recovery of neurological function, enhancement of the total effective rate in clinic, and improvement of activities of daily living. GRADE evaluation results showed that the quality of evidence was from low quality to very low quality. In conclusion, in the treatment of acute cerebral infarction, P. notoginseng saponins can improve the clinical efficacy, with a good safety but a not high methodological quality and a low evidence quality. It is suggested that high-quality clinical studies shall be further carried out to provide evidence-based basis for the application of P. notoginseng saponins in the treatment of acute cerebral infarction.

Systematic Review and Meta-Analysis on Randomized Controlled Trials on Efficacy and Safety of Panax Notoginseng Saponins in Treatment of Acute Ischemic Stroke.

OBJECTIVE: To assess the efficacy and safety of PNS on antiplatelet therapy in the treatment of AIS. METHODS: We searched 7 literature databases and 2 clinical studies databases for randomized controlled studies (RCTs) evaluating PNS as an adjuvant therapy for AIS. Relevant studies were retrieved and screened, and data were extracted independently by two reviewers. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool. Meta-analysis was carried out with the Rev Man 5.4 software. RESULTS: Of 8267 records identified, 43 RCTs met our inclusion criteria (n = 4170 patients). Patients assigned to PNS with conventional treatments (CTs) had improved functional independence at 90 days compared with those assigned to CTs alone (RR = 1.87, 95% CI = 1.37, to 2.55, P < 0.0001). Patients who received PNS combined with CTs showed significantly high improvements in neurological function among individuals with AIS on the neurologic deficit score (NDS) (MD CSS = -5.71, 95% CI = -9.55 to -1.87, P=0.004; MD NIHSS = -3.94, 95% CI = -5.65 to -2.23, P < 0.00001). The results also showed PNS contributed to a betterment in activities of daily living (ADL) on the Barthel index (MD day 10 BI = 4.86, 95% CI = 2.18, to 7.54, P < 0.00001; MD day 14 BI = 13.92, 95% CI = 11.46 to 16.38, P < 0.00001; MD day 28 BI = 7.16, 95% CI = 0.60, to 13.72, P < 0.00001). In addition, PNS, compared with CTs alone, could significantly improve overall response rate (ORR) (RR NIHSS = 1.20, 95% CI = 1.16, to 1.24, P < 0.00001; RR CSS = 1.15, 95% CI = 1.08, to 1.24, P < 0.0001), hemorheological parameters, maximum platelet aggregation rate (MPAR) (MD = -6.82, 95% CI = -9.62 to -4.02, P < 0.00001), platelet parameters (MD PLT = 4.85, 95% CI = 1.82 to 7.84, P=0.002; MD MPV = -0.79, 95% CI = -1.09 to -0.48, P < 0.00001), and serum CD62P (MD = -0.21, 95% CI = -0.29 to -0.13, P < 0.00001). The incidence of adverse reactions in PNS was lower than that in the control group (RR = 0.62, 95% CI = 0.39 to 0.97, P=0.04). Adverse reactions in the PNS were mild adverse reactions. CONCLUSION: PNS may be effective and safe in treating AIS on ameliorating neurological deficit, improving activities of daily living function, and enhancing antiplatelet effects. However, more high-quality evidence is needed before it can be recommended for routine antiplatelet therapy in patients with AIS.

Improvement of long-term clinical outcomes by successful PCI in the very elderly women with ACS.

BACKGROUND: Whether very elderly women with acute coronary syndromes (ACS) should receive aggressive percutaneous coronary intervention (PCI) is still controversial. We assessed the effectiveness and long-term clinical outcomes of successful PCI in this population and identified prognostic factors which might contribute to the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in the very elderly female PCI cohort. METHODS: Female ACS patients aged ≥ 80 years were consecutively enrolled (n = 729) into the study. All the patients were divided into female PCI group (n = 232) and medical group (n = 497). MACCE was followed up, including non-fatal myocardial infarction (MI), stroke, heart failure requiring hospitalization (HFRH), cardiovascular (CV) death, and the composite of them. After propensity score matching (1:1), the incidences of MACCE were compared between the two groups. Clinical and coronary artery lesion characteristics were compared between the female PCI patients with (n = 56) and without MACCE (n = 176). Multivariate Cox regression analysis was performed to identify risk factors which independently associated with MACCE in the female PCI patients. MACCE of male PCI patients, who aged ≥ 80 years and hospitalized in the same period (n = 264), was also compared with that of the female PCI patients. RESULTS: A total of 32% very elderly female ACS patients received PCI in the present study. (1) Compared to female medical group, PCI procedure significantly alleviated the risks of MACCE: non-fatal MI (6.2% vs. 20.2%, P < 0.001), HFRH (10.9% vs. 22.5%, P = 0.012), CV death (12.4% vs. 28.7%, P < 0.001) and the composite MACCE (24.0% vs. 44.2%, P < 0.001) during the median follow-up period of 36 months. (2) Between very elderly female and male PCI patients, there were no significant differences in occurrence of MACCE (P = 0.232) and CV death (P = 0.951). (3) Multivariate Cox analysis revealed that ST-segment elevation myocardial infarction (STEMI) (HR 1.944, 95% CI 1.11-3.403, P = 0.02) and elevated log- N-Terminal pro-brain natriuretic peptide (NT-proBNP) (HR 1.689, 95% CI 1.029-2.773, P = 0.038) were independently associated with the incidence of MACCE in the female PCI patients. CONCLUSIONS: PCI procedure significantly attenuated the risk of MACCE and improved the long-term clinical outcomes in very elderly female ACS patients. Aggressive PCI strategy may be reasonable in this population.

Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

PURPOSE: This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). RESULTS: Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis-free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05). CONCLUSION: Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

The treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

WHAT IS KNOWN AND OBJECTIVE: In recent years, the resistance of Mycoplasma pneumoniae to macrolide antibiotics has increased significantly. The health systems are facing significant challenges in carrying out the diagnosis and treatment of refractory Mycoplasma pneumoniae pneumonia in children. Levofloxacin is suitable for treating infectious diseases in various systems but limited in children due to arthropathy issues in weight-bearing joints. This study aimed to evaluate the efficacy and safety of levofloxacin in children with macrolide-resistant Mycoplasma pneumoniae pneumonia. METHODS: We retrospectively enrolled six confirmed cases of refractory Mycoplasma pneumoniae pneumonia who were admitted in the paediatric respiratory ward of Shandong provincial hospital Affiliated to Shandong first Medical University between 1st January 2020 and 29th February 2020. Levofloxacin was given to the patients through the intravenous or oral route as per the following dosages :<5 years, 8-10 mg/kg q12 h; >5 years, 8-10 mg/kg, qd for 10 days. The clinical data were collected and analysed. RESULTS AND DISCUSSION: The average age of the enrolled cases was six years and nine months (range, four years, and seven months to eleven years and seven months). All cases were found to be drug-resistant and were treated with azithromycin combined with antibacterial drugs. Levofloxacin was used in the patient's refractory to macrolide antibiotics. The temperature of five cases returned to normal 1-2 days after treatment with levofloxacin, and the imaging of the four cases showed expected improvements. The gastrointestinal symptoms, neurological manifestations, joint symptoms, blood parameters, liver and kidney functions, and exercise conditions of the children were closely monitored. The follow-up time of the patients ranged from one week to five months. No drug-related adverse reactions were observed in patients during treatment or during follow-up. WHAT IS NEW AND CONCLUSION: The clinical symptoms and imaging significantly improved after treatment with levofloxacin, and no drug-related adverse reactions were observed. Levofloxacin proved to be an effective and safe drug in the treatment of children with macrolide-resistant mycoplasma pneumonia. This study will provide a reference for evaluating the efficacy and safety of levofloxacin in the paediatric population.