Is short-term and long-term exposure to black carbon associated with cardiovascular and respiratory diseases? A systematic review and meta-analysis based on evidence reliability.

OBJECTIVE: Adverse health effects of fine particles (particulate matter2.5) have been well documented by a series of studies. However, evidences on the impacts of black carbon (BC) or elemental carbon (EC) on health are limited. The objectives were (1) to explored the effects of BC and EC on cardiovascular and respiratory morbidity and mortality, and (2) to verified the reliability of the meta-analysis by drawing p value plots. DESIGN: The systematic review and meta-analysis using adapted Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and p value plots approach. DATA SOURCES: PubMed, Embase and Web of Science were searched from inception to 19 July 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Time series, case cross-over and cohort studies that evaluated the associations between BC/EC on cardiovascular or respiratory morbidity or mortality were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently selected studies, extracted data and assessed risk of bias. Outcomes were analysed via a random effects model and reported as relative risk (RR) with 95% CI. The certainty of evidences was assessed by adapted GRADE. The reliabilities of meta-analyses were analysed by p value plots. RESULTS: Seventy studies met our inclusion criteria. (1) Short-term exposure to BC/EC was associated with 1.6% (95% CI 0.4% to 2.8%) increase in cardiovascular diseases per 1 µg/m3 in the elderly; (2) Long-term exposure to BC/EC was associated with 6.8% (95% CI 0.4% to 13.5%) increase in cardiovascular diseases and (3) The p value plot indicated that the association between BC/EC and respiratory diseases was consistent with randomness. CONCLUSIONS: Both short-term and long-term exposures to BC/EC were related with cardiovascular diseases. However, the impact of BC/EC on respiratory diseases did not present consistent evidence and further investigations are required. PROSPERO REGISTRATION NUMBER: CRD42020186244.

Impact of short-term exposure to extreme temperatures on diabetes mellitus morbidity and mortality? A systematic review and meta-analysis.

The relationship between diabetes mellitus and short-term exposure to extreme temperatures remains controversial. A systematic review and meta-analysis were performed to assess the association between extreme temperatures and diabetes mellitus morbidity and mortality. PubMed, Embase, the Cochrane Library, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched since inception to January 1, 2019, and updated on November 17, 2020. The results were combined using random effects model and reported as relative risk (RR) with 95% confidence interval (CI). In total, 32 studies met the inclusion criteria. (1) Both heat and cold exposures have impact on diabetes. (2) For heat exposure, the subgroup analysis revealed that the effect on diabetes mortality (RR=1.139, 95% CI: 1.089-1.192) was higher than morbidity (RR=1.012, 95% CI: 1.004-1.019). (3) With the increase of definition threshold, the impact of heat exposure on diabetes rose. (4) A stronger association between heat exposure and diabetes was observed in the elderly (≥ 60 years old) (RR=1.040, 95% CI: 1.017-1.064). In conclusion, short-term exposure to both heat and cold temperatures has impact on diabetes. The elderly is the vulnerable population of diabetes exposure to heat temperature. Developing definitions of heatwaves at the regional level are suggested.

Clinical Outcomes of Proximal Gastrectomy versus Total Gastrectomy for Proximal Gastric Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: The extent of optimal gastric resection for proximal gastric cancer (PGC) continues to remain controversial, and a final consensus is yet to be met. The current study aimed to compare the perioperative outcomes, postoperative complications, and overall survival (OS) of proximal gastrectomy (PG) versus total gastrectomy (TG) in the treatment of PGC through a meta-analysis. METHODS: We systematically searched PubMed, Embase, The Cochrane Library, and Web of Science for articles published in English since database establishment to October 2019. Evaluated endpoints were perioperative outcomes, postoperative complications, and long-term survival outcomes. RESULTS: A total of 2,896 patients in 25 full-text articles were included, of which one was a prospective randomized study, one was a clinical phase III trial, and the rest were retrospective comparative studies. The PG group showed a higher incidence of anastomotic stenosis (OR = 2.21 [95% CI: 1.08-4.50]; p = 0.03) and reflux symptoms (OR = 3.33 [95% CI: 1.85-5.99]; p < 0.001) when compared with the TG group, while no difference was found in PG patients with double-tract reconstruction (DTR). The retrieved lymph nodes were clearly more in the TG group (WMD = -10.46 [95% CI: -12.76 to -8.17]; p < 0.001). The PG group was associated with a better 5-year OS relative to TG with 11 included studies (OR = 1.35 [95% CI: 1.03-1.77]; p = 0.03). After stratification for early gastric cancer and PG with DTR groups, however, there was no significant difference between the 2 groups (OR = 1.35 [95% CI: 0.59-2.45]; p = 0.62). CONCLUSION: In conclusion, PG was associated with a visible improved long-term survival outcome for all irrespective of tumor stage, while a similar 5-year OS for only early gastric cancer patients between the 2 groups. Future randomized clinical trials of esophagojejunostomy techniques, such as DTR following PG, are expected to prevent postoperative complications and assist surgeons in the choice of surgical approach for PGC patients.

Corrigendum: ß-Sitosterol and Gemcitabine Exhibit Synergistic Anti-Pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3ß Signaling.

[This corrects the article DOI: 10.3389/fphar.2018.01525.].

Overexpression of Pyruvate Kinase M2 in Tumor Tissues Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with a high degree of malignancy and a poor prognosis. The aim of this study was to investigate the relationship between expression of pyruvate kinase M2 (PKM2) and prognosis in patients with HCC. The expression levels of PKM2 and PKM1 in 86 cases of HCC were detected by immunohistochemistry. An H score was used to evaluate the expression of PKM, and all patients were further divided into PKM high-expression and PKM low-expression groups. The relationship between PKM2 expression and the clinicopathological parameters and prognosis of patients were subsequently analyzed. Our data suggested that the expression level of PKM2 was significantly higher in HCC tissues than in adjacent tissues and the negatively expression of PKM1 in HCC tissues. Kaplan-Meier analysis revealed that PKM2 expression was strongly associated with survival in HCC patients (P = 0.001). The patients in the PKM2 high-expression group had significantly shorter survival times than the patients in the PKM2 low-expression group (hazard ratio for death, 2.358; 95% confidence interval [1.156, 4.812]; P = 0.018). In conclusion, these data indicate that PKM2 expression in HCC tissue samples can be used as a prognostic factor for patients with HCC and that high PKM2 expression is correlated with a poor prognosis in HCC patients.

The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a Bayesian network meta-analysis of 58 randomized controlled trials.

AIMS: The aim is to evaluate the efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4-I: sitagliptin, saxagliptin, linagliptin, vildagliptin and alogliptin) in patients with type 2 diabetes. METHODS: We searched the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), and the Wanfang Database from inception to April, 2018. Randomized controlled trials were included if they compared the different versions of DPP4-I with each other or with placebo in treatment of type 2 diabetes. Bayesian network meta-analysis and pairwise meta-analysis were performed to evaluate the efficacy and safety of the different kinds of DPP4-I and placebo. The data were analyzed using STATA 12.0 and WinBUGS1.4 software. RESULTS: We identified 58 eligible studies (with 31356 patients) involving 14 treatment arms. Indirect comparison results showed that except for alogliptin, a decrease was found for all DPP4-I versus the placebo for hemoglobin A1c (HbA1c) with vildagliptin50 twice daily (BID) showing the highest probability. Linagliptin5 once daily (QD) decreased the level of fasting plasma glucose (FPG) the most for all DPP4-I versus the placebo; when comparing them with each other, alogliptin25QD was more effective when compared with sitagliptin100QD and vildaglipti50BID; linagliptin5qd had the highest decrease impact on body mass index (BMI). Except for hypoglycemia and upper respiratory tract infection (URTI), there are no statistical significance on incidence of adverse events and the body weight when DPP4-I are compared with each other or with placebo. CONCLUSION: Our network meta-analysis presents the associations of DPP4-I versus placebos on HbA1c, FPG, 2 h postprandial blood glucose (2HPPG), BMI, body weight and adverse events. DPP4-I have a lowering effect on the glycemic level (HbA1c, FPG), especially vildaglipti50BID and linagliptin10QD, respectively. Besides, linagliptin5QD has the greatest probabilities of reducing BMI. In addition, DPP4-I were associated with not increasing the incidence of adverse events. Among them, vildagliptin100QD and sitagliptin100QD have the lowest probability in reducing the incidence of hypoglycemia and URTI, respectively.

A systematic review of questionnaires about patient's values and preferences in clinical practice guidelines.

OBJECTIVE: We conducted a systematic review to evaluate questionnaires about patient's values and preferences to provide information on the most appropriate questionnaires to be used when developing clinical practice guidelines. METHODS: A systematic literature search of the Cochrane Library, MEDLINE, Embase, Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure, and the Wanfang Database was performed to identify studies on questionnaires evaluating patient's values and preferences. The articles that used fully structured questionnaires or scales with standardized questions and answer options were included. We assessed the questionnaires' construction and content with a psychometric methodology and summarized the domains and items about patient's preferences and values. RESULTS: A total of 7,008 records were retrieved by the search strategy and scanned, and 20 articles were finally included. Of these, 10 (50%) articles described the process of item generation and only four questionnaires (20%, 4/20) mentioned the pilot testing. Regarding "validity", seven questionnaires (35%, 7/20) assessed validity and only one (5%, 1/20) questionnaire assessed internal consistency, with Cornbrash's α values of 0.74-0.87. For "acceptability", the time to complete the questionnaires ranged from 10 to 30 minutes and only nine studies (45%, 9/20) reported the response rates. In addition, the results of domains and items about patient's preferences and values showed that the "effectiveness" domain was the most considered item in the patient's value questionnaire followed by "safety", "prognosis", and others, whereas the least considered domain was "physician's experience". CONCLUSION: Only a few studies have developed questionnaires with rigorous psychometric methods to measure patient's preferences and values. Currently, still there is no valid or reliable questionnaire for patient's preferences and values for use when developing clinical practice guidelines. Further study should be conducted to develop standardized instruments to measure patient's preferences and values. This study provides the domains and items that may be used in formulating questionnaires about patient's preferences and values.

ß-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3ß Signaling.

ß-sitosterol (BS), a major bioactive constituent present in plants, has shown potent anti-cancer activity against many human cancer cells, but its activity in pancreatic cancer (PC) cells has rarely been reported. Gemcitabine (GEM) is one of the first-line drugs for PC therapy, however, the treatment effect is not sustained due to prolonged drug resistance. In this study, we firstly studied the anti-PC activity and the mechanism of BS alone and in combination with GEM in vitro and in vivo. BS effectively inhibited the growth of PC cell lines by inhibiting proliferation, inducing G0/G1 phase arrest and apoptosis, suppressed the NF- kB activity, and increased expression of the protein Bax but decreased expression of the protein Bcl-2. Moreover, BS inhibited migration and invasion and downregulated epithelial-mesenchymal transition (EMT) markers and AKT/GSK-3ß signaling pathways. Furthermore, the combination of BS and GEM exhibited a significant synergistic effect in MIAPaCa-2 and BXPC-3 cells. More importantly, the combined treatment with BS and GEM lead to significant growth inhibition of PC xenografts. Overall, our data revealed a promising treatment option for PC by the combination therapy of BS and GEM.