Assessment of comorbidities and prognosis in patients with COPD diagnosed with the fixed ratio and the lower limit of normal: a systematic review and meta-analysis.

BACKGROUND: Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) is not uniform, COPD guidelines recommend fixed ratio (FR), whereas ATS and ERS define airflow obstruction based on lower limit of normal (LLN). We aim to determine if there is difference between the two diagnostic criteria for morbidity, mortality, exacerbation. METHODS: Four databases and all relevant studies from the references were searched from inception to June 25, 2019, to find studies that described the rate of comorbidity, the exacerbation rates, mortality in COPD patients. Data analysis was performed using STATA/SE 14.0 and followed the standard of Cochrane Collaboration. A sensitivity analysis was performed to find the source of heterogeneity. RESULTS: Thirteen studies and 154,447 participants were finally included in this meta-analysis. The 11 cohort studies and 2 cross-sectional studies were all high-quality. Patients with airflow limitation according to either FR or LLN had higher mortality (HRFR+/LLN- = 1.27, 95% CI = 1.14-1.42; HRFR-/LLN+ = 1.83, 95% CI = 1.17-2.86) than those who met neither criteria. When compared with the FR-/LLN- criteria, those who met the FR criteria were more likely to exacerbate (HR FR+/LLN- = 1.64, 95% CI = 1.09-2.46; HR FR-/LLN+ = 1.58, 95% CI = 0.70-3.55). The meta-analysis for comorbidities showed no significant difference between patients who met neither criteria and those who met LLN or FR criteria. CONCLUSION: The patients with airflow limitations according to FR were more likely to exacerbate than those with LLN only. Patients that met either FR or LLN were more likely to have higher mortality than FR-/LLN-. There was no difference between the FR+/LLN- and FR-/LLN+ groups for the occurrence of comorbidities.

Deletion of soluble epoxide hydrolase attenuates mice Hyperoxic acute lung injury.

BACKGROUND: Recent studies reported that soluble epoxide hydrolase (sEH) plays an important role in lung diseases. However, the role of sEH in hyperoxia-induced ALI is unclear. METHODS: ALI was induced by exposure to 100% oxygen in an airtight cage for 72 h in wild-type (WT) and sEH gene deletion (EPHX2-/-) mice. ALI was assessed by the lung dry/wet ratio, alveolar capillary protein leak, and the infiltration of inflammatory cells in the lung. RESULTS: Hyperoxia elevated sEH activity in WT mice. Simultaneously, epoxyeicosatrienoic acids (EETs) levels were decreased in WT mice exposed to hyperoxia. However, the level of EETs was increased in EPHX2-/- mice exposed to hyperoxia. Hyperoxia induced pulmonary edema and inflammation were dampened in EPHX2-/- mice compared with WT mice. Decreased expression of Kelch-like ECH-associated protein 1 (Keap1) was found in EPHX2-/- mice exposed to hyperoxia. Hyperoxia-induced the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) was enhanced in EPHX2-/- mice compared with WT mice. Simultaneously, the activities of heme oxygenase-1 and superoxide dismutase were elevated in EPHX2-/- mice. The levels of reactive oxygen species were inhibited in EPHX2-/- mice compared with WT mice exposed to hyperoxia. CONCLUSIONS: sEH is a harmful factor for hyperoxic ALI. The beneficial effect of sEH gene deletion is associated with the elevation of EETs and regulation of Nrf2/Keap1 signal pathway.

NT-proBNP in Different Patient Groups of COPD: A Systematic Review and Meta-Analysis.

Purpose: NT-proBNP, a peptide biomarker synthesized and secreted by cardiomyocytes in response to cardiac load, has gained attention in recent years for its potential role in respiratory diseases. Chronic Obstructive Pulmonary Disease (COPD), a chronic and progressive inflammatory condition affecting the respiratory system, is frequently associated with comorbidities involving the cardiovascular system. Consequently, the aim of this systematic review and meta-analysis was to evaluate the variations in NT-proBNP levels across distinct patient groups with COPD and establish a foundation for future investigations into the precise clinical significance of NT-proBNP in COPD. Methods: The search databases for this study were conducted in PubMed, Excerpt Medica database (Embase), Web of Science (WOS), and Cochrane Library databases. Databases were searched for studies on the predictive value of NT-proBNP in adult COPD patients. Results: A total of 29 studies (8534 participants) were included. Patients with stable COPD exhibit elevated levels of NT-proBNP [standardized mean difference(SMD) [95CI%]=0.51 [0.13,0.89]; p=0.0092]. COPD patients with predicted forced expiratory volume in 1 s (FEV1) < 50% exhibit significantly elevated levels of NT-proBNP compared to those with FEV1 ⩾50%[SMD [95CI%]=0.17 [0.05,0.29]; p=0.0058]. NT-proBNP levels were significantly higher in acute exacerbations (AECOPD) compared to patients with stable COPD [SMD [95CI%]=1.18 [0.07,2.29]; p=0.037]. NT-proBNP levels was significantly higher in non-survivors than in survivors of hospitalised AECOPD patients [SMD [95CI%]=1.67 [0.47,2.88]; p=0.0063]. Both COPD patients with pulmonary hypertension(PH) [SMD [95CI%]=0.82 [0.69,0.96]; p<0.0001] and chronic heart failure(CHF) [SMD [95CI%]=1.49 [0.96,2.01]; p<0.0001] showed higher NT-proBNP level. Conclusion: NT-proBNP, a biomarker commonly used in clinical practice to evaluate cardiovascular disease, demonstrates significant variations in different stages of COPD and during the progression of the disease. The fluctuations in NT-proBNP levels could be indicative of the severity of pulmonary hypoxia and inflammation and cardiovascular stress among COPD patients. Therefore, assessing NT-proBNP levels in COPD patients can aid in making informed clinical decisions.

Treatment of a patient with severe lactic acidosis and multiple organ failure due to mitochondrial myopathy: A case report.

BACKGROUND: Mitochondrial myopathy is a rare genetic disease with maternal inheritance that may involve multiple organ systems. Due to the lack of typical characteristics, its clinical diagnosis is difficult, and it is often misdiagnosed or even missed. CASE SUMMARY: The patient was a young college student. When he presented at the hospital, he had severe lactic acidosis, respiratory failure, and shock with multiple organ dysfunction syndrome (MODS). He was treated by mechanical ventilation, veno-arterial extracorporeal membrane oxygenation, and other organ support. However, his condition continued to worsen. After a thorough and detailed medical and family history was taken, a mitochondrial crisis was suspected. A muscle biopsy was taken. Further genetic testing confirmed a mitochondrial gene mutation (TRNL1 3243A>G). The final diagnosis of mitochondrial myopathy was made. Although there is no known specific treatment, intravenous methylprednisone and intravenous immunoglobulin were started. The patient's shock eventually improved. The further course was complicated by severe infection in multiple sites, severe muscle weakness, and recurrent MODS. After 2 mo of multidisciplinary management and intensive rehabilitation, the patient could walk with assistance 4 mo after admission and walk independently 6 mo after admission. CONCLUSION: More attention should be paid to mitochondrial myopathy to avoid missed diagnosis and misdiagnosis.

High-Flow Nasal Cannula Oxygen Therapy versus Non-Invasive Ventilation for AECOPD Patients After Extubation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: To evaluate the clinical efficacy of high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) after extubation. Research Methods: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: reintubation rate, mortality, complication rate, and ICU length of stay. Results: Eight studies were included, with a total of 612 subjects, including 297 in the HFNC group and 315 in the NIV group. The effect of HFNC and NIV on the reintubation rate of AECOPD patients after extubation, RR (1.49 [95% CI,0.95 to 2.33], P = 0.082). Subgroup analysis with or without hypercapnia according to the included AECOPD population, with hypercapnia, RR (0.69 [95% CI,0.33 to 1.44], P=0.317), without hypercapnia, RR (2.61 [95% CI,1.41 to 4.83], P=0.002). Mortality, RR (0.92 [95% CI,0.56 to 1.52], P = 0.752). ICU length of stay, MD (-0.44 [95% CI,-1.01 to 0.13], P = 0.132). Complication rate, RR (0.22 [95% CI,0.13 to 0.39], P = 0.000). After subgroup analysis, the reintubation rate of HFNC and NIV has no statistical difference in patients with hypercapnia, but NIV can significantly reduce the reintubation rate in patients without hypercapnia. In the outcome measures of complication rate, HFNC significantly reduced complication rate compared with NIV. In mortality and ICU length of stay, analysis results showed that HFNC and NIV were not statistically different. Conclusion: According to the available evidence, the application of HFNC can be used as an alternative treatment for NIV after extubation in AECOPD patients with hypercapnia, but in the patients without hypercapnia, HFNC is less effective than NIV.

Efficacy and cardiovascular safety of LAMA in patients with COPD: a systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is at present the third leading cause of death in the world. Long-acting muscarinic antagonist (LAMA) is widely used as a bronchodilator in patients with COPD. However, there is controversy concerning their cardiovascular safety. This meta-analysis aims to assess the efficacy and cardiovascular safety of LAMAs versus placebo in patients with COPD. We searched Pub Med, Embase, Cochrane Library, and Web of Science to identify studies that compared LAMA with placebo in patients with COPD. Twenty-one studies involving 24,987 participants were finally included in the analysis. There was no significant difference in the incidence of all adverse events (risk ratio (RR)=1.01, 95% CI 1.00 to 1.02, I2=15.2%) and cardiovascular events (RR=0.98, 95% CI 0.88 to 1.09, I2=4.9%) in patients treated with LAMAs versus placebo. LAMAs significantly improved trough forced expiratory volume in 1 s (weighted mean difference (WMD)=0.12, 95% CI 0.10 to 0.14, I2=86.6%), Transitional Dyspnea Index (WMD=0.75, 95% CI 0.56 to 0.94, I2=0%), and St. George's Respiratory Questionnaire (WMD=‒2.50, 95% CI ‒3.32 to ‒1.69, I2=39.8%). Moreover, LAMAs significantly reduced the incidence of exacerbation in patients with COPD (RR=0.85, 95% CI 0.79 to 0.91, I2=69.9%). LAMAs are safe therapy and play a pivotal role in improving lung function, dyspnea, and health status, and reducing the exacerbation in patients with COPD.

Low-dose theophylline in addition to ICS therapy in COPD patients: A systematic review and meta-analysis.

BACKGROUND: A synergism has been reported between theophylline and corticosteroids, wherein theophylline increases and restores the anti-inflammatory effect of inhaled corticosteroids (ICS) by enhancing histone deacetylase-2 (HDAC) activity. Several studies have explored the efficacy of low-dose theophylline plus ICS therapy on chronic obstructive pulmonary disease (COPD) but the results are discrepant. METHOD: We conducted searches in electronic database such as PubMed, Web Of Science, Cochrane Library, and Embase to find out original studies. Stata/SE 15.0 was used to perform all data analysis. RESULT: A total of 47,556 participants from 7 studies were included in our analysis and the sample size of each study varied from 24 to 10,816. Theophylline as an add-on therapy to ICS was not associated with the reduction of COPD exacerbations (HR: 1.08, 95% CI: 0.97 to 1.19, I2 = 95.2%). Instead, the theophylline group demonstrated a higher hospitalization rate (HR: 1.12, 95% CI: 1.10 to 1.15, I2 = 20.4%) and mortality (HR: 1.19, 95% CI: 1.14 to 1.25, I2 = 0%). Further, the anti-inflammatory effect of low-dose theophylline as an adjunct to ICS on COPD was controversial. Besides, the theophylline group showed significant improvement in lung function compared with the non-theophylline group. CONCLUSION: Based on current evidence, low-dose theophylline as add-on therapy to ICS did not reduce the exacerbation rate. Instead, the hospitalization rate and mortality increased with theophylline. Thus, we do not recommend adding low-dose theophylline to ICS therapy in COPD patients. TRIAL REGISTRATION: PROSPERO Registration CRD42021224952.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression.

Correction to "Liu LP, Sheng XP, Shuai TK, Zhao YX, Li B, Li YM. Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression. World J Gastroenterol 2018; 24: 4565-4577 [PMID: 30386106 DOI: 10.3748/wjg.v24.i40.4565]." In this article, we have identified some of the images in Figure 2A, C, E, G, and I are identical to the images in Figures 1B, 2A, 3B, 3E, and 3G of another paper entitled "Liu L, Zhao Y, Fan G, Shuai T, Li B, Li Y. Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogenactivated protein kinase signalling in human gastric cancer cells.", which was published by us in the Molecular Medicine Reports in December, 2018 [PMID: 30320396 DOI: 10.3892/mmr.2018.9558]. The reason why we asked to replace the pictures was that when we were simultaneously preparing to submit our two different articles to the World Journal of Gastroenterology (WJG) and Molecular Medicine Reports, we uploaded the wrong pictures to the WJG, which were same as those submitted to the Molecular Medicine Reports. We apologize for this negligence and any inconvenience that this may cause. We would be grateful if you could replace the wrong pictures with the correct ones attached.

The clinical value of suPAR in diagnosis and prediction for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is positively correlated with immune system activity. Inflammation can promote the development of chronic obstructive pulmonary disease (COPD). Therefore, this study conducted a systematic review and meta-analysis to assess the association between suPAR levels and the pathogenesis of COPD, and further assess the exact clinical value of suPAR in COPD. METHODS: PubMed, Excerpt Medica Database (Embase), Web of Science (WOS), and Cochrane Library databases were searched for studies that reported the value of suPAR diagnosis for adult COPD patients. RESULTS: A total of 11 studies were included, involving 4520 participants. Both COPD patients with predicted forced expiratory volume in 1 s (FEV1)⩾80% [weighted mean difference (WMD) = 320.25; 95% confidence interval (CI): 99.79-540.71] and FEV1 < 80% (WMD = 2950.74; 95% CI: 2647.06-3254.43) showed higher suPAR level. The sensitivity and specificity of suPAR for diagnosis of COPD were 87% and 79%, respectively, and AUC was 84%. This can not only effectively identify acute exacerbation of COPD (AECOPD) in a healthy population (WMD = 3114.77; 95% CI: 2814.66-3414.88), but also has the potential to distinguish AECOPD from stable COPD (WMD = 351.40; 95% CI: 215.88-486.93). There was a significant decrease of suPAR level after treatment [WMD = -1226.97; 95% CI: -1380.91- (-1073.03)]. CONCLUSION: suPAR as a novel biomarker has potential for early diagnosis of COPD and prediction of AECOPD. There is a potential correlation between the level of suPAR and the state of COPD, which may also indicate the early state and severity of COPD. When the suPAR level of COPD patients is further increased, the risk of acute exacerbation increases and should be highly valued. This also shows potential as a measure of treatment response, and as a guide to the clinical management in COPD. The reviews of this paper are available via the supplemental material section.

Risk factors for new-onset atrial fibrillation in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: New-onset atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD) is associated with an accelerated decline in lung function, and a significant increase in mortality rate. A deeper understanding of the risk factors for new-onset AF during COPD will provide insights into the relationship between COPD and AF and guide clinical practice. This systematic review and meta-analysis is designed to identify risk factors for new-onset AF in patients with COPD, and to formulate recommendations for preventing AF in COPD patients that will assist clinical decision making. METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies, which reported the results of potential risk factors for new-onset AF in COPD patients. RESULTS: Twenty studies involving 8,072,043 participants were included. Fifty factors were examined as potential risk factors for new-onset AF during COPD. Risk factors were grouped according to demographics, comorbid conditions, and COPD- and cardiovascular-related factors. In quantitative analysis, cardiovascular- and demographic-related factors with a greater than 50% increase in the odds of new-onset AF included age (over 65 years and over 75 years), acute care encounter, coronary artery disease, heart failure and congestive heart failure. Only one factor is related to the reduction of odds by more than 33.3%, which is black race (vs white). In qualitative analysis, the comparison of the risk factors was conducted between COPD-associated AF and non-COPD-associated AF. Cardiovascular-related factors for non-COPD-associated AF were also considered as risk factors for new-onset AF during COPD; however, the influence tended to be stronger during COPD. In addition, comorbid factors identified in non-COPD-associated AF were not associated with an increased risk of AF during COPD. CONCLUSIONS: New-onset AF in COPD has significant demographic characteristics. Older age (over 65 years), males and white race are at higher risk of developing AF. COPD patients with a history of cardiovascular disease should be carefully monitored for new-onset of AF, and appropriate preventive measures should be implemented. Even patients with mild COPD are at high risk of new-onset AF. This study shows that risk factors for new-onset AF during COPD are mainly those associated with the cardiovascular-related event and are not synonymous with comorbid factors for non-COPD-associated AF. The pathogenesis of COPD-associated AF may be predominantly related to the cardiac dysfunction caused by the chronic duration of COPD, which increases the risk of cardiovascular-related factors and further increases the risk of AF during COPD. PROSPERO REGISTRATION NUMBER: CRD42019137758.

DECAF score as a mortality predictor for acute exacerbation of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

OBJECTIVES: This study was conducted to assess the association between the Dyspnea, Eosinopenia, Consolidation, Acidemia and Atrial Fibrillation (DECAF) scores and the prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), to evaluate the specific predictive and prognostic value of DECAF scores and to explore the effectiveness of different cut-off values in risk stratification of patients with AECOPD. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Adult patients diagnosed with AECOPD (over 18 years of age). PRIMARY AND SECONDARY OUTCOME MEASURES: Electronic databases, including the Cochrane Library, PubMed, the Embase and the WOS, and the reference lists in related articles were searched for studies published up to September 2019. The identified studies reported the prognostic value of DECAF scores in patients with AECOPD. RESULTS: Seventeen studies involving 8329 participants were included in the study. Quantitative analysis demonstrated that elevated DECAF scores were associated with high mortality risk (weighted mean difference=1.87; 95% CI 1.19 to 2.56). In the accuracy analysis, DECAF scores showed good prognostic accuracy for both in-hospital and 30-day mortality (area under the receiver operating characteristic curve: 0.83 (0.79-0.86) and 0.79 (0.76-0.83), respectively). When the prognostic value was compared with that of other scoring systems, DECAF scores showed better prognostic accuracy and stable clinical values than the modified DECAF; COPD and Asthma Physiology Score; BUN, Altered mental status, Pulse and age >65; Confusion, Urea, Respiratory Rate, Blood pressure and age >65; or Acute Physiology and Chronic Health Evaluation II scores. CONCLUSION: The DECAF score is an effective and feasible predictor for short-term mortality. As a specific and easily scored predictor for patients with AECOPD, DECAF score is superior to other prognostic scores. The DECAF score can correctly identify most patients with AECOPD as low risk, and with the increase of cut-off value, the risk stratification of DECAF score in high-risk population increases significantly.

Prevalence of chronic obstructive pulmonary disease at high altitude: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Recently, several studies have investigated the prevalence of chronic obstructive pulmonary disease (COPD) at high altitude (>1,500 m). However, much remains to be understood about the correlation between altitude and COPD. We aimed to summarize the prevalence of COPD at high-altitudes and find out if altitude could be a risk factor for COPD. METHODS: We searched PubMed/Medline, Cochrane Library, Web of Science, SCOPUS, OVID, Chinese Biomedical Literature Database (CBM) and Embase databases from inception to April 30th, 2019, with no language restriction. We used STATA 14.0 to analyze the extracted data. A random-effect model was used to calculate the combined OR and 95% CI. Heterogeneity was assessed by the I 2 statistic versus P-value. We performed a subgroup analysis to analyze possible sources of heterogeneity. The Egger's test and the Begg's test were used to assess any publication bias. RESULTS: We retrieved 4,574 studies from seven databases and finally included 10 studies (54,578 participants). Males ranged from 18.8% to 49.3% and the population who smoked ranged from 3.3% to 53.3%. The overall prevalence of COPD at high-altitude was 10.0% (95% CI [0.08-0.12], P < 0.001). In a subgroup analysis, based on different regions, the results showed that the prevalence in Asia was higher than that in Europe and America. Seven studies compared the relationship between the prevalence of COPD at high-altitudes and the lowlands. The results showed that altitude was not an independent risk factor for the prevalence of COPD (ORadj = 1.18, 95% CI [0.85-1.62], P = 0.321). There was no publication bias among the studies. CONCLUSIONS: Our study found a higher prevalence of COPD at high-altitudes than those from average data. However, altitude was not found to be an independent risk factor for developing COPD (PROSPERO Identifier: CRD42019135012).

Extracorporeal Shock Wave Therapy for Treating Foot Ulcers in Adults With Type 1 and Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Extracorporeal shock wave therapy (ESWT) as a new adjuvant therapy has shown a potential capability to promote diabetic foot ulcer (DFU) healing. The purpose of this study was to assess the efficacy and safety of ESWT on the healing of DFUs. The Cochrane Library, PubMed, Embase, Web of Science, China Biology Medicine and reference lists were searched for studies published up to December 2018. Randomized controlled trials of any design, including ESWT for patients with DFU, were included. Two reviewers extracted data, including the wound surface area (WSA), percentage of re-epithelialization, population of complete cure and unchanged and other related outcomes. Eight randomized controlled trials (N=339) were included. ESWT was found to be associated with a greater reduction of WSA by 1.54 cm2, and increase of re-epithelialization by 26.31%. A greater population with complete cure was found at the end of treatment (risk ratio [RR] = 2.22; 95% confidence interval [CI], 1.46 to 3.40); however, there was no statistically significant difference at the end of follow up (p=0.052). It can also reduce treatment inefficiency by 4.8-fold (95% CI, 0.12 to 0.37). In addition, ESWT also showed a higher superiority than hyperbaric oxygen therapy in the population for complete cure and unchanged ulcer (RR=1.83; 95% CI, 1.14 to 2.94 and RR=0.25; 95% CI, 0.13 to 0.48, respectively). ESWT is a feasible adjuvant treatment for DFUs. It can effectively improve the complete cure rate, shorten the healing period of DFUs and significantly reduce treatment ineffectiveness. This can provide new therapeutic ideas for clinical practice of intractable and recurrent DFUs.

The Diagnostic and Prognostic Value of suPAR in Patients with Sepsis: A Systematic Review and Meta-Analysis.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) has the potential to diagnose infectious diseases. Due to the lack of reliable biomarkers and the importance of timely diagnosis for sepsis treatment, we conducted this systematic review and meta-analysis to evaluate the value of suPAR diagnosis and prognosis for sepsis. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for studies, which reported the value of suPAR diagnosis and/or prognosis in patients with sepsis. RESULTS: A total of 30 studies involving 6,906 patients were included. Sensitivity and specificity of suPAR for diagnosing sepsis were 0.76 [95% confidence interval (CI), 0.63-0.86] and 0.78 (95% CI, 0.72-0.83), respectively. The area under the summary receiver-operating characteristic curve (AUC) was 0.83 (95% CI, 0.80-0.86). Pooled sensitivity and specificity for predicting mortality were 0.74 (95% CI, 0.67-0.80) and 0.70 (95% CI, 0.63-0.76), respectively, with AUC of 0.78 (95% CI, 0.74-0.82). In addition, AUC for differentiating sepsis from systemic inflammatory response syndrome (SIRS) was 0.81 (95% CI, 0.77-0.84), and the sensitivity and specificity were 0.67 (95% CI, 0.58-0.76) and 0.82 (95% CI, 0.73-0.88), respectively. CONCLUSION: suPAR is a feasible biomarker for timely diagnosis and prognosis of sepsis. Compared with effective value of procalcitonin (PCT) identified by previous meta-analysis, suPAR has similar clinical guiding value, whereas suPAR exhibits higher specificity, which can facilitate the deficiencies of PCT. suPAR also shows a diagnostic value in differentiating sepsis from SIRS. Considering the lack of biomarkers for sepsis and the similar clinical value of suPAR and PCT, suPAR should be considered as a biomarker in clinical practice for sepsis.

Association between Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic kidney disease (CKD) has become a global public health problem with a high prevalence and mortality. There is no sensitive and effective markers for chronic kidney disease. Previous studies proposed suPAR as an early predict biomarker for chronic kidney disease, but the results are controversial. Therefore, the purpose of the current meta-analysis is to evaluate the association between suPAR and CKD. METHODS: We searched the PubMed, Embase, Cochrane Library databases, and Web of Science before May 1, 2019. The search was based on the key words including suPAR and CKD. Data are extracted independently according to standard format, and quality analysis is performed. We extracted the concentration of suPAR and hazard rate (HR) values of mortality, cardiovascular disease, and end-stage renal disease. RESULTS: There were 14 studies fulfilling the criteria. The concentration of suPAR was higher in patients with CKD than that in the control group (P < 0.001; SMD: -2.17; 95% CI: -2.71, -1.63; I 2 = 67.4%). SuPAR had a higher risk of mortality (P=0.001; HR: 1.72; 95% CI: 1.24, 2.39; I 2 = 68.0%). The higher suPAR level increased the risk of cardiovascular disease (P < 0.001; HR: 3.06; 95% CI: 2.21, 4.22; I 2 = 0.0%) and the risk of end-stage renal disease (P < 0.001; HR: 1.40; 95% CI: 1.22, 1.60; I 2 = 0.0%). CONCLUSIONS: Monitoring suPAR concentrations may be used for early diagnosis and prognosis for patients with CKD, and the higher suPAR increased the risk of mortality, cardiovascular events, and end-stage renal disease.

Serum soluble urokinase type plasminogen activated receptor and focal segmental glomerulosclerosis: a systematic review and meta-analysis.

OBJECTIVES: Soluble urokinase plasminogen activated receptor (suPAR) is a biomarker that may predict the occurrence of focal segmental glomerulosclerosis (FSGS); however, there is still controversy about whether suPAR can predict FSGS. In this study, we performed a systematic evaluation and meta-analysis to prove whether suPAR can predict FSGS, and to detect a threshold concentration of suPAR that can be used to diagnose FSGS. In addition, a threshold concentration of suPAR for the diagnosis of FSGS was proposed. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We systematically searched PubMed, Embase, Cochrane Library, Web of Science and China Biology Medicine databases for studies published from the inception dates to 1 December 2018. ELIGIBILITY CRITERIA: (1) Data involving the suPAR level were from blood samples; (2) FSGS was diagnosed by biopsy; and (3) randomised controlled trials, cohort studies, case-control studies and cross-sectional studies. DATA EXTRACTION AND SYNTHESIS: Initially, a total of 364 studies were searched, among which 29 studies were finally included. In addition, seven studies described the cut-off value of suPAR, which ranged from 2992.6 to 5500 pg/mL. RESULTS: The results showed that the suPAR levels in the primary FSGS group were significantly higher when compared with that in the normal control group (p<0.001; standard mean difference (SMD): 2.56; 95% CI 1.85 to 3.28), and significant differences were observed in the secondary FSGS and in the normal control group (p<0.001; SMD: 1.68; 95% CI 1.37 to 1.98). A suPAR concentration of 3000 pg/mL may be the best threshold for the diagnosis of primary FSGS (sensitivity=0.72; specificity=0.88; area under the curve=0.85). CONCLUSION: Our results suggested that suPAR might be a potential biomarker for predicting primary and secondary FSGS. In addition, our data showed that a suPAR concentration of 3000 pg/mL might be used as a threshold for the diagnosis of FSGS. TRIAL REGISTRATION NUMBER: CRD42019120948.

A prognostic role for non-thyroidal illness syndrome in chronic renal failure:a systematic review and meta-analysis.

BACKGROUND: Chronic renal failure (CRF) is a serious disease that has become a burden on global and local economics and public health. In addition, non-thyroidal illness syndrome (NTIS) has become increasingly more prevalent in CRF patients. MATERIALS AND METHODS: A data search was conducted on the PubMed/Medline, Cochrane Library, Web of Science, Embase, and CBM databases to identify studies up to November 1st, 2018, that compared low T3 and normal T3 levels in patients with CRF. Data analysis was done by calculating the relative risks (RR) and 95% confidence intervals (95% CI) and continuous variables were described by weighted mean difference (WMD) and 95% CI. The efficacy outcomes included renal function and mortality. The Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality scale were used to assess the quality of the cohort and cross-sectional studies, respectively. A funnel plot was used to identify publication bias. RESULTS: Seventeen studies with a total of 4593 patients were finally included in the analysis. Among the 17 studies, 11 reported the mortality of CRF patients with low T3 and normal T3 levels. Subgroups were assigned according to different follow-up times and different methods of treatment. The mortality rate in the low T3 group was much higher than in the normal T3 group. 11 studies reported creatinine (Cr) results in patients with low T3 and normal T3 levels and our analysis found no significant differences between the two groups (95%CI: 0.46-0.25; P-heterogeneity = 0.000; P = 0.559). Five studies reported uric acid results and we found no significant differences between the two groups (95%CI: 0.08-0.22; P-heterogeneity = 0.438; P = 0.377). Five studies reported the urea levels in the two groups and our analysis found no significant differences (95%CI: 1.60-1.23; I2 = 0.0%; P-heterogeneity = 0.498;P = 0.798). CONCLUSION: Low T3 had a greater impact on the short-term prognosis of patients with CRF than on the long-term prognosis. NTIS did not cause substantial kidney damage.

Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogen­activated protein kinase signalling in human gastric cancer cells.

Helicobacter pylori (H. pylori) infection is the most important factor in the development of gastric cancer. Heparanase (HPA) is involved in tissue remodelling and cell migration, which leads to inflammation and tumour metastasis. The current study aimed was to explore whether a H. pylori infection leads to an increase in the level of HPA in gastric cancer and to investigate the specific mechanism underlying this association. Reverse transcription­polymerase chain reaction and western blotting were used to detect HPA mRNA and protein expression, respectively, in MKN­45 cells infected by H. pylori, MKN­45 cells treated with the mitogen­activated protein kinase (MAPK) inhibitor SB203580 and MKN­45 cells transfected with small interfering RNA against HPA. MAPK and nuclear factor (NF)­κB expression were determined by western blotting in the different cells group. Cell Counting Kit­8, Transwell method, and Scratch and Clone tests were conducted to detect proliferation, invasion, migration and clone formation ability of gastric cancer cells. It was demonstrated that HPA mRNA expression was highest at 6 h post­infection, while the expression of the HPA protein was highest at 24 h post­infection in H. pylori­infected gastric cancer cells. Furthermore, it was demonstrated that H. pylori infection significantly enhanced the expression of MAPK and NF­κB in MKN­45 cells at the mRNA and protein levels. SB203580 significantly decreased the expression of NF­κB in MKN­45 cells infected with H. pylori. Exposure to SB203580 also significantly decreased the expression of HPA. In the present study, the inhibition of HPA significantly lowered H. pylori­induced cell proliferation, suggesting that H. pylori infection induces the proliferation of gastric cancer cells through the upregulation of HPA. Taken together, the results of the present study demonstrated that HPA serves a critical role in the development of gastric cancer in H. pylori­infected cells, which may be an important mechanism through which H. pylori infection leads to gastric cancer. In addition, H. pylori infection promotes the proliferation, invasion and metastasis of gastric cancer cells through the upregulation of HPA expression, and this is likely mediated via the MAPK and NF­κB signalling pathways. These data suggest that HPA can be used as a therapeutic target in gastric cancer, particularly in cases induced by H. pylori infection.

Long non­coding RNA lnc­GNAT1­1 inhibits gastric cancer cell proliferation and invasion through the Wnt/ß­catenin pathway in Helicobacter pylori infection.

The aim of the present study was to investigate the effect of long non­coding (lnc)­G protein subunit α transducin 1 (GNAT1)­1 in gastric cancer cells infected with Helicobacter (H.) pylori. Reverse transcription­quantitative polymerase chain reaction was used to assess lnc­GNAT1­1 expression in normal gastric and gastric cancer cells infected with H. pylori. The overexpression of lnc­GNAT1­1 in SGC­7901 and MNK45 cells was induced by transfection. Migration and invasion assays were performed in transfected gastric cancer cells to evaluate the effect of lnc­GNAT1­1. Histological and western blot analyses were used to determine the alterations in the Wnt/ß­catenin signaling pathway protein expression. Cells transfected with lnc­GNAT1­1 were used to initiate gastric cancer tumor xenografts to compare tumor growth in mice inoculated with untransfected cells. The results revealed that H. pylori infection significantly downregulated lnc­GNAT­1 expression. Lnc­GNAT1­1 overexpression inhibited gastric cancer cell migration and invasion. Wnt/ß­catenin pathway protein expression was decreased by lnc­GNAT1­1 overexpression. In addition, lnc­GNAT1­1 overexpression reduced tumor growth. Thus, lnc­GNAT1­1 is downregulated in gastric cancer infected with H. pylori and lnc­GNAT1­1 overexpression inhibited gastric cancer growth through the Wnt/ß­catenin signaling pathway.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression.

AIM: To detect the mechanisms of Helicobacter pylori (H. pylori) infection in the invasion and metastasis of gastric cancer (GC). METHODS: Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase (HPA) and mitogen-activated protein kinase (MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival (OS) and relapse-free survival (RFS) of GC patients were estimated by the Kaplan-Meier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS: H. pylori infection was observed in 70 of 99 patients with GC (70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK (P < 0.05); HPA expression was relevant to MAPK expression (P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing (P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases (P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION: H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.