mGluR5 promotes the progression of multiple myeloma in vitro via Ras-MAPK signaling pathway.

BACKGROUND: Multiple myeloma (MM) is a malignant plasma cancer which remains difficult to be cured. Recently, numerous research studies have appeared, exploring MM from molecular level. However, there is no study about the impact of metabotropic glutamate receptors (mGluRs), especially mGluR5, on MM progression. Thus, the present research was dedicated to the exploration of the influence of mGluR5 on MM. OBJECTIVES: In this research, we used quantitative real-time polymerase chain reaction (qRT-PCR) to check the gene expression in MM, western blot assay to check the protein expression of the gene, MTT assay to quantify the cell viability, and flow cytometry (FCM) apoptosis method to evaluate cell apoptosis in order to acquire the results. The purpose was to assess the role of mGluR5 in MM cells. MATERIAL AND METHODS: The qRT-PCR was used and it was found that mGluR5 was overexpressed in MM cell lines and MM tissues compared to normal ones. To better observe the function of mGluR5 in MM, cell viability and apoptosis were checked using MTT and FCM apoptosis assays after the treatment with agonists and antagonists. RESULTS: Agonist-induced mGluR5 upregulation could promote MM cell viability and inhibit apoptosis. The same results were obtained through MTT and FCM apoptosis assays after upregulation and downregulation of mGluR5 by transfection. To further investigate the inner mechanism, the effect of mGluR5 on Ras-MAPK pathway was checked using western blot. It was found that the upregulation of mGluR5 could activate the Ras-MAPK pathway. CONCLUSIONS: The mGluR5 might be involved in promoting cell proliferation and inhibiting cell apoptosis in MM. It can be an essential biomarker in the screening for MM and a potential part of future MM therapies.

Comparative efficacy and safety of antipseudomonal ß-lactams for pediatric febrile neutropenia: A systematic review and Bayesian network meta-analysis.

BACKGROUND: Antipseudomonal ß-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal ß-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal ß-lactams for pediatric FN. METHODS: PubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal ß-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763. RESULTS: Eighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal ß-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate. CONCLUSIONS: Meropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.

Clinical efficacy and safety of Huachansu injection combination with platinum-based chemotherapy for advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Huachansu injection (HCS) is a widely used traditional Chinese medicine for advanced non-small cell lung cancer (NSCLC) to alleviate the adverse drug reactions (ADRs) and enhance the clinical efficacy of chemotherapy. OBJECTIVE: To evaluate the efficacy and safety of HCS as an adjunctive treatment to platinum-based chemotherapy (PBC) for advanced NSCLC. METHODS: A systematic review and meta-analysis were conducted according to PRISMA guidelines. A total of nine databases were searched to select randomized controlled trials (RCTs) of HCS plus PBC to treat NSCLC from inception to October 10, 2020. RCTs on HCS plus PBC vs PBC alone for advanced NSCLC were included. Dichotomous data were pooled as risk ratio (RR) with 95% confidence intervals. RCTs compared to HCS plus PBC vs PBC alone were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), and secondary outcomes were survival rate, quality of life (QOL), and adverse drug reactions (ADRs). GRADE software was used to access the quality of evidence. RESULTS: A total of 32 RCTs, including 2753 patients, were included. Compared to PBC alone, HCS plus PBC improved the ORR, DCR, 1- and 2-year survival rates, and QOL and alleviated neutropenia, thrombocytopenia, nausea, vomiting, anemia, liver injury, renal injury, and alopecia. CONCLUSIONS: Compared to PBC alone, HCS plus PBC improved the clinical efficacy and alleviated the ADRs in advanced NSCLC patients. Considering the limitations of the included RCTs, high-quality trials with longer follow-ups are needed to further confirm the results.

Carbapenems vs alternative antibiotics for the treatment of complicated urinary tract infection: A systematic review and network meta-analysis.

BACKGROUND: Complicated urinary tract infections (cUTI) are universal reasons for hospitalization, and highly likely to develop into sepsis or septic shock. Carbapenem antibiotics with potentially higher efficacy or with fewer and milder side effects have increased in popularity, but evidence is limited by a scarcity of randomized controlled trials (RCTs) comparing different carbapenem antibiotics for cUTI. Network meta-analysis is a useful tool to compare multiple treatments when there is limited or no direct evidence available. OBJECTIVE: The aim of this study is to compare the efficacy and safety of different carbapenems with alternative antibiotics for the treatment of cUTI. METHODS: Pubmed, Medline, CENTRAL, and Embase were searched in November 2018. Studies of cUTI patients receiving carbapenem were included. We performed network meta-analysis to estimate the risk ratio (RR) and 95% credible interval (CrI) from both direct and indirect evidence; traditional meta-analysis was also performed. Primary outcomes were clinical and microbiological treatment success. RESULTS: A total of 19 studies and 7380 patients were included in the analysis. Doripenem (DOPM) was associated with lower clinical treatment success rates than other carbapenems. Although the efficacy of other carbapenems by RRs with 95% CrIs did not show statistical differences, the cumulative rank probability indicated that meropenem/vaborbactam (MV), ertapenem (ETPM), and biapenem (BAPM) had higher clinical and microbiological treatment success rates; imipenem/cilastatin (IC) and MV showed higher risk of adverse events (AEs). CONCLUSIONS: MV was associated with higher treatment success rates for cUTI, especially for cUTI caused by carbapenem-resistant uropathogens, but also with higher risk of AEs. Our findings suggest MV as a first-choice treatment of carbapenem-resistant cUTI. ETPM, BAPM, and meropenem (MEPM) is another reasonable choice for cUTI empiric therapy.

Safety and efficacy of combined use of propofol and etomidate for sedation during gastroscopy: Systematic review and meta-analysis.

BACKGROUND: Sedation with etomidate or propofol alone during gastroscopy has many side effects. A systematic review and meta-analysis were conducted to evaluate the safety and efficacy of the combined use of propofol and etomidate for sedation during gastroscopy. METHODS: PubMed, Embase, Medline (via Ovid SP), Cochrane library databases, CINAHL (via EBSCO), China Biology Medicine disc (CBMdisc), Wanfang, VIP, and China National Knowledge Infrastructure (CNKI) databases were systematically searched. We included randomized controlled trials (RCTs) comparing the combined use of propofol and etomidate vs etomidate or propofol alone for sedation during gastroscopy. Data were pooled using the random-effects models or fixed-effect model based on heterogeneity. RESULTS: Fifteen studies with 2973 participants were included in the analysis. Compared to propofol alone, the combined use of propofol and etomidate possibly increased recovery time (SMD = 0.14, 95% CI = 0.04-0.24; P = .005), and the risk for myoclonus (OR = 3.07, 95% CI = 1.73-5.44; P < .001), injection pain, and nausea and vomiting. Furthermore, compared to propofol alone, the combination of propofol and etomidate produced an apparent beneficial effect for mean arterial pressure (MAP) after anesthesia (SMD = 1.32, 95% CI = 0.38-2.26; P = .006), SPO2 after anesthesia (SMD = 0.99, 95% CI = 0.43-1.55; P < .001), apnea or hypoxemia (OR = 0.16, 95% CI = 0.08-0.33; P < .001), injection pain, and body movement. Further, compared to etomidate alone, the combination of propofol and etomidate reduced the risk for myoclonus (OR = 0.15, 95% CI = 0.11-0.22; P < .001), body movement, and nausea and vomiting. CONCLUSION: The combination of propofol and etomidate might increase recovery time vs that associated with propofol, but it had fewer side effects on circulation and respiration in patients undergoing gastroscopy. The combined use of propofol and etomidate can improve and produce an apparent beneficial effect on the adverse effects of propofol or etomidate alone, and it was safer and more effective than propofol or etomidate alone.

FTY720 attenuates iron deposition and glial responses in improving delayed lesion and long-term outcomes of collagenase-induced intracerebral hemorrhage.

Most intracerebral hemorrhage (ICH) survivors have poor long-term outcomes, such as cognitive deficits and depression. Delayed lesions of ICH include neuron loss and white matter injury and the pathology of the lesions involves iron deposition and glial responses, which contribute to depressive-like behavior and cognitive impairment in animals. This study aimed to investigate the effects of FTY720 (0.3 mg/kg/day for 4 weeks) on iron deposition, glial responses, histological abnormalities and behavioral dysfunction in mice with ICH. The primary adverse long-term outcomes in our study of ICH mice were depressive-like behavior and impaired recognition memory. We found that FTY720 safely ameliorated depressive-like behavior and impaired recognition without affecting recovery of grip function and locomotor activity 28 days post-ICH. Moreover, we measured neuron loss, white matter lesions, lesion volume and iron deposition at day 28, which were attenuated in the FTY720-treated group compared to the ICH-control group, without changing initial hematoma volume on day 1 post-ICH. Long-term elevation of glial responses, including microglia activity and astrogliosis with tumor necrosis factor alpha (TNFα) expression was demonstrated by Western blot and immunofluorescence staining, which we found was attenuated by FTY720 treatment. Hence, FTY720 could become a novel therapeutic agent for improving long-term outcomes after ICH.

CdS nanoparticles-enhanced chemiluminescence and determination of baicalin in pharmaceutical preparations.

CdS nanoparticles (CdS NPs) of different sizes were synthesized by the citrate reduction method. It was found that CdS NPs could enhance the chemiluminescence (CL) of the luminol-potassium ferricyanide system and baicalin could inhibit CdS NPs-enhanced luminol-potassium ferricyanide CL signals in alkaline solution. Based on this inhibition, a flow-injection CL method was established for determination of baicalin in pharmaceutical preparations and human urine samples. Under optimized conditions, the linear range for determination of baicalin was 5.0 x 10(-6) to 1.0 x 10(-3) g/L. The detection limit at a signal-to-noise ratio of 3 was 1.7 x 10(-6) g/L. CL spectra, UV-visible spectra and transmission electron microscopy (TEM) were used to investigate the CL mechanism. The method described is simple, selective and obviates the need of extensive sample pretreatment.

Determination of bisphenol A in water via inhibition of silver nanoparticles-enhanced chemiluminescence.

Sensitive detection of trace bisphenol A (BPA) in water samples has been accomplished via inhibition of luminol chemiluminescence (CL) by BPA on the silver nanoparticles (AgNPs)-enhanced luminol-KMnO(4) CL system for the first time. Under the optimized experimental conditions, the CL intensity was found to be proportional to the concentration of BPA ranging from 1.0 × 10(-8) to 5.0 × 10(-5) g L(-1). The detection limit (3σ) was estimated to be 1 × 10(-9) g L(-1). Such a concentration level is approximately 1-4 orders of magnitude lower than those reported by other methods. The feasibility of the method for determination of BPA in real water samples has been demonstrated. Via examining CL and UV-vis spectra of the CL system, possible mechanism inherent in the AgNPs-enhanced CL assay and the follow-up inhibition of BPA on the above system was proposed. The method described herein is simple, selective and obviates the need of extensive sample pretreatment.