Evaluation on the traditional safe use of Kochiae Fructus oriented by antioxidant properties and oral safety of its ethanolic extract.

Kochiae Fructus (KF) is a traditional Chinese medicine, which has been used to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc. In order to fully understand the traditional medicinal value of KF, we evaluated the antioxidant properties and oral safety of its ethanolic extract. Considering flavonoids and phenolics in medicinal plants generally have strong antioxidant activity, we firstly detected the total flavonoids and phenolics contents of KFEE and its fractions. Secondly, we evaluated the antioxidant activities of KFEE and its fractions. Finally, we evaluated the oral safety of KFEE by the acute and 28-day subacute toxicities. The n-butanol fraction (ENBF) possessed the highest phenolics and flavonoids with values of 77.30 ± 3.17 mg gallic acid equivalents/g and 228.81 ± 7.56 mg rutin equivalents/g, respectively. The results of antioxidant tests showed that ENBF possessed potent antioxidant ability. Among them, the high antioxidation capacity observed in ENBF could be attributed to its rich content of flavonoids and phenolics. The results of toxicological studies showed that the LD50 value of KFEE was 6000 mg/kg BW, and the no observed adverse effect level (NOAEL) of KFEE was 600 mg/kg BW. According to the standards of the American Academy of Sciences for the classification of toxic substances, KFEE can be classified as practically non-toxic substance, which provided valuable evidence for the oral safety of KF as a natural aging delay medicine.

Antioxidant, Anti-Inflammatory and Anti-Diabetic Activities of Tectona grandis Methanolic Extracts, Fractions, and Isolated Compounds.

Tectona grandis is a traditional Dai medicine plant belonging to the Lamiaceae family, which can be used to treat malaria, inflammation, diabetes, liver disease, bronchitis, tumors, cholelithiasis, jaundice, skin disease and as an anti-helminthic. To find more novel therapeutic agents contained in this medicinal plant, the antioxidant, anti-inflammatory and anti-diabetic activities of T. grandis methanolic extract, fractions and compounds were evaluated. In this study, 26 compounds were isolated from the leaves and branches of T. grandis. Their structures were identified based on extensive spectral experiments, including NMR, ESI-MS and comparison with published spectral data. Among them, compounds 1-2, 4-6, 9-14 and 16-22 were reported for the first time for this plant. The antioxidant activity screening results showed that compounds 5, 15 and 23 had potent antioxidant capacities, with SC50 values from 0.32 to 9.92 µmol/L, 0.92 to 1.10 mmol Trolox/L and 1.02 to 1.22 mmol Trolox/L for DPPH, ABTS and FRAP, respectively. In addition, their anti-inflammatory effects were investigated by releasing TNF-α, IL-1ß and IL-6 through the use of mouse monocytic macrophages (RAW 264.7). Compounds 1, 13, 18 and 23 had the effects of reducing the expression of inflammatory factors. Compounds 13 and 18 were reported for the first time for their anti-inflammatory activities. Furthermore, the methanolic extract (ME), petroleum ether extract (PEE) and EtOAc extract (EAE) of T. grandis showed significant glucose uptake activities; compounds 21 and 23 significantly promoted glucose uptake of 3T3-L1 adipocytes at 40 µM. Meanwhile, compounds 4, 5 and 7 showed significant inhibitory activities against α-glucosidase, with IC50 values of 14.16 ± 0.34 µmol/L, 19.29 ± 0.26 µmol/L and 3.04 ± 0.08 µmol/L, respectively. Compounds 4 and 5 were reported for the first time for their α-glucosidase inhibitory activities. Our investigation explored the possible therapeutic material basis of T. grandis to prevent oxidative stress and related diseases, especially inflammation and diabetes.

Triterpenoids from Kochiae Fructus: Glucose Uptake in 3T3-L1 Adipocytes and α-Glucosidase Inhibition, In Silico Molecular Docking.

In this study, three new triterpenes (1-3) and fourteen known triterpenoids (4-17) were isolated from the ethanol extract of Kochiae Fructus, and their structures were elucidated by analyzing UV, IR, HR-ESI-MS, 1D, and 2D NMR spectroscopic data. Among them, compounds 6, 8, and 11-17 were isolated for the first time from this plant. The screening results of the glucose uptake experiment indicated that compound 13 had a potent effect on glucose uptake in 3T3-L1 adipocytes at 20 µM. Meanwhile, compounds 3, 9 and 13 exhibited significant inhibitory activities against α-glucosidase, with IC50 values of 23.50 ± 3.37, 4.29 ± 0.52, and 16.99 ± 2.70 µM, respectively, and their α-glucosidase inhibitory activities were reported for the first time. According to the enzyme kinetics using Lineweaver-Burk and Dixon plots, we found that compounds 3, 9 and 13 were α-glucosidase mixed-type inhibitors with Ki values of 56.86 ± 1.23, 48.88 ± 0.07 and 13.63 ± 0.42 µM, respectively. In silico molecular docking analysis showed that compounds 3 and 13 possessed superior binding capacities with α-glucosidase (3A4A AutoDock score: -4.99 and -4.63 kcal/mol). Whereas compound 9 showed +2.74 kcal/mol, which indicated compound 9 exerted the effect of inhibiting α-glucosidase activity by preferentially binding to the enzyme-substrate complex. As a result, compounds 3, 9 and 13 could have therapeutic potentials for type 2 diabetes mellitus, due to their potent hypoglycemic activities.

PD-1/PD-L1 inhibitor plus chemotherapy versus standard of care in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor plus chemotherapy vs standard of care (SoC) treatment in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M-SCCHN). METHODS: Randomized controlled trials (RCTs) that investigated PD-1/PD-L1 inhibitor plus chemotherapy vs SoC as first-line treatment for R/M-SCCHN were searched from electronic databases (PubMed, Embase and Cochrane Library). The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: In total, three phase 3 RCTs (KEYNOTE-048, CAPTAIN-1st, and JUPITER-02; n = 1120) with three PD-1 inhibitors (pembrolizumab, camrelizumab and toripalimab) were included in the analysis. Compared with SoC, PD-1 inhibitor plus chemotherapy significantly prolonged PFS (hazard ratio [HR] 0.66, 95% CI 0.40-0.93, p < 0.001) and OS (HR 0.73, 95% CI 0.60-0.86, p < 0.001) of patients. There was no statistical differences in ORR (odds ratio [OR] 1.26; 95% CI 0.97-1.64, p = 0.086), grade 3 or higher AEs (OR 0.77, 95% CI 0.50-1.17, p = 0.221), and treatment-related deaths (OR 1.34, 95% CI 0.60-2.98, p = 0.470) between the two groups. CONCLUSION: PD-1 inhibitor plus chemotherapy showed more survival benefit than SoC in the first-line treatment for R/M-SCCHN, with a similar safety profile.

Efficacy and safety of adjuvant therapy with PD­1/PD­L1 inhibitors in cancer.

Anti-programmed cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) antibodies have been widely used in cancers. The present study aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in human cancers. Studies were searched from Cochrane Library, PubMed and Embase databases. Randomized controlled trials (RCTs) that investigated adjuvant therapy with anti-PD-1/PD-L1 agents in solid cancers were eligible for inclusion. As the primary focus of the meta-analysis, clinical outcome measures including overall survival (OS), disease-free survival (DFS), and adverse events (AEs) were analyzed by Stata 15.0 software. A total of six RCTs (n=4,436) met the inclusion criteria. The DFS [hazard ratio (HR)=0.71; 95% confidence interval (CI): 0.63-0.78; P<0.001] and OS (HR=0.66, 95% CI: 0.46-0.86, P<0.001) of patients were significantly prolonged by adjuvant immunotherapy. Subgroup analysis indicated that significantly improved DFS was observed in patients treated with different anti-PD-1/PD-L1 drugs (nivolumab, pembrolizumab, or atezolizumab), as well as in those with different tumors (melanoma, urothelial carcinoma, esophageal or gastroesophageal junction cancer, or renal cell carcinoma), and PD-L1 status [negative (<1%) or positive (≥1%)]. However, PD-1/PD-L1 inhibitors was associated with increased ≥ grade 3 treatment-related AEs (odds ratio=1.63; 95% CI: 1.20-2.21; P=0.002). The available evidence suggests that adjuvant therapy with PD-1/PD-L1 inhibitors provided more survival benefit than placebo for patients with cancer, with increased grade 3 or higher AEs. Prospero registration no. CRD42021290654.

Night Vision Anti-Halation Method Based on Infrared and Visible Video Fusion.

In order to address the discontinuity caused by the direct application of the infrared and visible image fusion anti-halation method to a video, an efficient night vision anti-halation method based on video fusion is proposed. The designed frame selection based on inter-frame difference determines the optimal cosine angle threshold by analyzing the relation of cosine angle threshold with nonlinear correlation information entropy and de-frame rate. The proposed time-mark-based adaptive motion compensation constructs the same number of interpolation frames as the redundant frames by taking the retained frame number as a time stamp. At the same time, considering the motion vector of two adjacent retained frames as the benchmark, the adaptive weights are constructed according to the interframe differences between the interpolated frame and the last retained frame, then the motion vector of the interpolated frame is estimated. The experimental results show that the proposed frame selection strategy ensures the maximum safe frame removal under the premise of continuous video content at different vehicle speeds in various halation scenes. The frame numbers and playing duration of the fused video are consistent with that of the original video, and the content of the interpolated frame is highly synchronized with that of the corresponding original frames. The average FPS of video fusion in this work is about six times that in the frame-by-frame fusion, which effectively improves the anti-halation processing efficiency of video fusion.

Kochiae Fructus: Evaluation on the antioxidant properties and oral safety of its water decoction.

Kochiae Fructus (KF) was listed as 'top grade' medicinal material by the 'Shennong's Herbal Classic of Materia Medica' and has been used in traditional Chinese medicine to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc. Our research focused on the antioxidant capability of water decoction and fractions from KF based on 2,2-iphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radical scavenging assay, the ferric reducing antioxidant power assay, and inhibitory effects on DNA and protein oxidative damage. The results of total phenolics and flavonoids contents showed that ethyl acetate fraction (EAF) possessed the highest phenolics and flavonoids with values of 112.90 ± 9.58 mg gallic acid equivalents/g and 329.60 ± 20.93 mg rutin equivalents/g, respectively. At the same time, the results of antioxidant capacities showed that EAF possessed best antioxidant abilities. In addition, in this work, we evaluated the oral safety of the water decoction of KF (KFWD) via the 14-day acute and 28-day subacute toxicity tests. The results of in vivo toxicity assessment showed that KFWD did not cause significant changes in the general clinical symptoms, hematology and biochemical parameters, organ weights, or histopathological appearances in mice or rats. In summary, the reason why KF has the traditional effect on delaying aging may be related to the fact that its rich in flavonoids and phenolics. Simultaneously, no toxicity was detected after acute or subacute treatment of KFWD, providing valuable evidence for the traditional safe use of KF.

Efficacy of immune checkpoint inhibitor as maintenance therapy for advanced or metastatic cancers: A meta-analysis of randomized controlled trials.

BACKGROUND: This study aimed to evaluate the efficacy of immune checkpoint inhibitors (ICIs) as maintenance therapy for advanced or metastatic cancers. METHODS: The PubMed, Embase, and Cochrane Library databases were searched for eligible randomized controlled trials. A meta-analysis of eligible studies investigating the outcomes including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) with a significance level set to 0.05 was performed. RESULTS: Five RCTs (n = 2828) were identified in this analysis. The pooled hazard ratios (HRs) of PFS and OS for ICI maintenance therapy were 0.88 (95% CI: 0.68-1.13, P = .31) and 0.82 (95% confidence interval [CI]: 0.74-0.92, P = .0005), respectively; the pooled odds ratio (OR) of ORR was 2.24 (95% CI: 1.23-4.09, P = .0008). Subgroup analysis indicated that anti-PD-L1 antibody significantly improved the OS (P = .0008), while anti-PD-1 and anti-PD-1 plus anti-cytotoxic T lymphocyte antigen 4 antibodies significantly prolonged the PFS of patients. CONCLUSION: ICI maintenance therapy enhanced the survival of patients with advanced or metastatic cancers.

In Vitro and In Vivo Evaluation of Antidiabetic Properties and Mechanisms of Ficus tikoua Bur.

In folk medicine, Ficus tikoua (F. tikoua) has been used to treat diabetes for a long time, but there is a rare modern pharmacological investigation for its antidiabetic effect and mechanisms. Our study aimed to evaluate its hypoglycemic effect using in vitro and in vivo experimental models and then explore the possible mechanisms. In the ethanol extracts and fractions of F. tikoua, n-butanol fraction (NBF) exhibited the most potent effect on inhibiting α-glucosidase activity (IC50 = 0.89 ± 0.04 µg/mL) and promoting glucose uptake in 3T3-L1 adipocytes. Further animal experiments showed that NBF could play an antidiabetic role by ameliorating random blood glucose, fasting blood glucose, oral glucose tolerance, HbA1c level, and islets damage in diabetic mice. Then, the activities of the five subfractions of NBF (NBF1-NBF5) were further evaluated; NBF2 showed stronger α-glucosidase inhibition activities (IC50 = 0.32 ± 0.05 µg/mL) than NBF. Moreover, NBF2 also possessed the ability to promote glucose uptake, which was mediated via P13K/AKT and AMPK pathways. This study demonstrated that F. tikoua possesses antidiabetic efficacy in vitro and in vivo and provided a scientific basis for its folk medicinal use. NBF2 might be potential natural candidate drugs to treat diabetes mellitus. It is the first time the antidiabetic activity and the potential mechanisms of NBF2 were reported.

Hypoglycemic and Antioxidant Properties of Extracts and Fractions from Polygoni Avicularis Herba.

Our research focused on the hypoglycemic capability and the possible mechanisms of extract and fractions from Polygoni Avicularis Herba (PAH) based on α-glucosidase, α-amylase inhibition assays, glucose uptake experiment, HPLC-MS analysis, and molecular docking experiment. In addition, DPPH, ABTS, and FRAP assays were used for determining the antioxidant capability. The results of total flavonoids and phenolics contents showed that ethyl acetate fraction (EAF) possessed the highest flavonoids and phenolics with values of 159.7 ± 2.5 mg rutin equivalents/g and 107.6 ± 2.0 mg galic acid equivalents/g, respectively. The results of in vitro hypoglycemic activity showed that all samples had effective α-glucosidase inhibition capacities, and EAF possessed the best inhibitory effect with IC50 value of 1.58 ± 0.24 µg/mL. In addition, n-butanol fraction (NBF) significantly promoted the glucose uptake rate of 3T3-L1 adipocytes. HPLC-MS analysis and molecular docking results proved the interactions between candidates and α-glucosidase. The results of antioxidation capacities showed that EAF possessed the best antioxidation abilities with DPPH, ABTS, and FRAP. In summary, the hypoglycemic activity of PAH might be related to the inhibition of α-glucosidase (EAF > PEF > NBF) and the promotion of glucose uptake in 3T3-L1 adipocytes (NBF). Simultaneously, the antioxidation capacity of PAH might be related to the abundant contents of flavonoids and other phenolics (EAF > PEF > NBF).

Antioxidant, Hypoglycemic and Molecular Docking Studies of Methanolic Extract, Fractions and Isolated Compounds from Aerial Parts of Cymbopogon citratus (DC.) Stapf.

Traditionally, Cymbopogon citratus is used to treat a variety of ailments, including cough, indigestion, fever, and diabetes. The previous chemical and bioactive research on C. citratus mainly focused on its volatile oil. In this study, 20 non-volatile known compounds were isolated from the dried aerial part of C. citratus, and their structures were elucidated by MS, NMR spectroscopy, and comparison with the published spectroscopic data. Among them, 16 compounds were reported for the first time from this plant. The screening results for antioxidant and α-glucosidase inhibitory activities indicated that compounds caffeic acid (5), 1-O-p-coumaroyl-3-O-caffeoylglycerol (8), 1,3-O-dicaffeoylglycerol (9) and luteolin-7-O-ß-D-glucopyranoside (12) had potent antioxidant capacities, with IC50 values from 7.28 to 14.81 µM, 1.70 to 2.15 mol Trolox/mol and 1.31 to 2.42 mol Trolox/mol for DPPH, ABTS, and FRAP, respectively. Meanwhile, compounds 8 and 9 also exhibited significant inhibitory activities against α-glucosidase, with IC50 values of 11.45 ± 1.82 µM and 5.46 ± 0.25 µM, respectively, which were reported for the first time for their α-glucosidase inhibitory activities. The molecular docking result provided a molecular comprehension of the interaction between compounds (8 and 9) and α-glucosidase. The significant antioxidant and α-glucosidase inhibitory activities of compounds 8 and 9 suggested that they could be developed into antidiabetic drugs because of their potential regulatory roles on oxidative stress and digestive enzyme.

LINC01806 mediated by STAT1 promotes cell proliferation, migration, invasion, and stemness in non-small cell lung cancer through Notch signaling by miR-4428/NOTCH2 axis.

BACKGROUND: Non-small cell lung cancer (NSCLC), the most primary lung cancer subtype, threatens human health globally. Long non-coding RNAs (lncRNAs) have been uncovered to affect multiple cancers progression. Nevertheless, the specific function of long intergenic non-protein coding RNA 1806 (LINC01806) in NSCLC remains elusive. METHODS: RT-qPCR and western blot were involved in this study. The influence of LINC01806 on NSCLC was assessed by in vitro and in vivo assays. Via ChIP, RNA pull down, RIP, and luciferase reporter assays, the in-depth cellular mechanisms of LINC01806 in NSCLC were explored. RESULTS: LINC01806 expression was high in NSCLC cell lines. Functionally, LINC01806 knockdown impeded cell proliferation, migration, invasion, and stemness, along with tumor growth. As for its mechanism, signal transducer and activator of transcription 1 (STAT1) activated LINC01806 transcription in NSCLC. Furthermore, LINC01806 sequestered microRNA-4428 (miR-4428) to enhance notch receptor 2 (NOTCH2) expression, thus activating Notch signaling pathway. Finally, in vitro and in vivo assays jointly validated that LINC01806 exerted its function in NSCLC development via miR-4428/NOTCH2 pathway. CONCLUSION: LINC01806 enhanced NOTCH2 expression to stimulate Notch signaling via sponging miR-4428, thereby facilitating NSCLC progression, which provided a novel mechanism for NSCLC therapeutic approaches.

The efficacy and safety of immune checkpoint inhibitor plus chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of immune checkpoint inhibitor (ICI) and chemotherapy (CT) versus CT alone in advanced non-small-cell lung cancer (NSCLC). METHODS: Databases (PubMed, Embase and Cochrane Library) were searched for relevant randomized controlled trials (RCTs). Clinical outcome measures including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3-5 treatment-related adverse events (AEs) were analyzed by Stata 15.0 software; significance level was 0.05. RESULTS: Eight RCTs involving 4227 patients were included. The results showed ICI + CT significantly improved OS (hazard ratio [HR] = 0.74, 95% CI: 0.62-0.85, p < 0.001), PFS (HR = 0.66, 95% CI: 0.57 - 0.75, p < 0.001) and ORR (odds ratio [OR] = 1.89; 95% CI, 1.43-2.49, p < 0.001) compared with CT alone. Subgroup analysis indicated that significantly longer OS was also observed in subgroups including combination regimens (pembrolizumab + CT, atezolizumab + CT, ipilimumab + CT, and nivolumab + ipilimumab + CT) and PD-L1 status [negative (< 1%), positive (≥ 1%), low (1-49%) and high (≥ 50%)]. However, ICI + CT showed signifcantly higher grade 3-5 treatment-related AEs than CT (OR = 1.46, 95% CI: 1.19 - 1.79, p < 0.001). CONCLUSIONS: ICI + CT showed better clinical efficacy than CT alone in patients with advanced NSCLC, with increased treatment-related AEs.

Antidiabetic potential of Catechu via assays for α-glucosidase, α-amylase, and glucose uptake in adipocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Catechu is the dry water extract of barked branches or stems from Senegalia catechu(L. F.)P. J. H. Hurter & Mabb, which is used as a hypoglycemic regulator in recent researches. Potential anti-hyperglycemic components and the putative mechanisms were evaluated in this investigation. AIM OF THE STUDY: Evaluated the hypoglycemic activity of Catechu via α-glucosidase, α-amylase inhibition assays, and glucose uptake in 3T3-L1 adipocytes. MATERIALS AND METHODS: The effects of Catechu on α-glucosidase, α-amylase inhibition assays and glucose uptake experiment were tested after the ethanol extract of Catechu (EE) was sequentially partitioned with petroleum ether (PEE), ethyl acetate (EAE), and n-butanol fractions (NBE). Next, HPLC-MS and traditional Chinese medicine (TCM) database were used to detect and analyze the primary active ingredients presented in hypoglycemic fraction. In addition, in silico molecular docking study was used to evaluate the candidates' inhibitory activity against α-glucosidase and α-amylase. RESULTS: The results of α-glucosidase and α-amylase inhibition assays indicated that all fractions, with the exception of PEE, presented significant inhibitory effects on α-glucosidase and α-amylase. The inhibitory effect of NBE on α-glucosidase was similar to the positive control (NBE IC50 = 0.3353 ± 0.1215 µg/mL; Acarbose IC50 = 0.1123 ± 0.0023 µg/mL). Furthermore, the inhibitory kinetics of α-glucosidase revealed that all fractions except for PEE belong to uncompetitive type. In silico molecular docking analysis showed that the main compositions of NBE ((-)-epicatechin, cyanidin, and delphinidin) possessed superior binding capacities with α-glucosidase (3WY1 AutoDock score: 4.82 kcal/mol; -5.59 kcal/mol; -5.63 kcal/mol) and α-amylase (4GQR AutoDock score: 4.80 kcal/mol; -5.89 kcal/mol; -4.26 kcal/mol), respectively. The results of glucose uptake experiment indicated that EE, PEE, EAE, and NBE without significant promotion effect on glucose uptake rate of 3T3-L1 adipocytes (P > 0.05). CONCLUSION: This study revealed that the hypoglycemic effect of Catechu might be related to the inhibitory effects of phenols on digestive enzymes (α-glucosidase and α-amylase), and the possible active phenols were (-)-epicatechin, cyanidin, delphinidin and their derivatives, which provided scientific evidences for Catechu's traditional use to treat T2DM.

Combination therapy with immune checkpoint inhibitors in advanced renal cell carcinoma: A meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the efficacy and safety of immune checkpoint inhibitor combination therapy in advanced renal cell carcinoma (RCC). METHODS: We searched PubMed/Embase/Cochrane Library for relevant randomized controlled trials (RCTs). Clinical outcome measures including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and adverse events (AEs) were analyzed by Stata 15.1 software. RESULTS: Seven RCTs involving 3461 patients were included. The pooled hazard ratios of OS and PFS for combination therapy were 0.67 (0.53-0.82, p < 0.001) and 0.68 (0.52-0.83, p < 0.001), respectively. Longer OS and PFS for combination therapy was also observed in the PD-L1 expression leve ≥1% group. The pooled odds ratios of ORRs and grade 3 or higher AEs were 2.31 (1.61-3.32, p < 0.001) and 0.94 (0.65-1.37, p = 0.753), respectively. CONCLUSIONS: Immune checkpoint inhibitor combination therapy showed more clinical benefit in the first-line treatment for advanced RCC, with a safety profile.

The efficacy and safety of combination therapy with immune checkpoint inhibitors in non-small cell lung cancer: A meta-analysis.

PURPOSE: Combination therapies with immune checkpoint blockade demonstrate promising antitumor activity and safety in Non-small Cell Lung Cancer (NSCLC). However, whether the combination therapy is superior to their monotherapies, and which combination regimen is most efficacious remain unknown. This meta-analysis aims to synthesize the current available evidences on the efficacy and safety of combination immunotherapy in patients with NSCLC. METHODS: PubMed, Embase and Cochrane Library were searched. Randomized controlled trials (RCTs) investigating combination therapy with immune checkpoint inhibitors in NSCLC were included. RESULTS: We identified nine RCTs including a total of 5,142 patients. The study showed that the pooled hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) for combination therapy were 0.74 (95% CI: 0.63-0.86, p = 0.001) and 0.65 (95% CI: 0.56-0.73, p = 0.004); the pooled odds ratios (ORs) of objective response rates (ORRs) and grade 3 or higher adverse events (AEs) were 1.51 (95% CI: 1.02-1.99, p < 0.001) and 1.30 (95% CI: 1.03-1.57, p = 0.007). Subgroup analysis showed that the OR of grade 3 or higher AEs for immunotherapy plus chemotherapy was higher than that of chemotherapy alone, but did not reach statistical significance (p = 0.061) , and there was PFS and OS benefit for either immunotherapy plus chemotherapy, double agent immunotherapy or immunotherapy plus targeted plus chemotherapy combination regimens. CONCLUSIONS: Combination therapy with immune checkpoint inhibitors showed more clinical benefit for patients with NSCLC, with increased grade 3 or higher AEs, but toxicities were manageable.

Microarray analysis reveals a potential role of lncRNA expression in remote ischemic preconditioning in myocardial ischemia-reperfusion injury.

The challenge to avoid or reduce cardiopulmonary bypass-related injuries in cardiovascular surgery remains a major issue. Remote ischemic preconditioning (RIPC) remains a promising strategy whose clinical applications appear to be significantly more realistic and extensive as compared with other conservative or surgical strategies. However, considering its underlying mechanism(s) are still unclear, novel ideas and methods must be explored to enhance its potential in clinical applications. Long noncoding RNAs (LncRNAs) are a kind of RNAs that have been implicated in the occurrence and development of cardiovascular diseases. The differently expressed LncRNAs and their biological effects during RIPC have not been explored previously. In this study, mouse and human LncRNA microarrays were used to investigate the expression signatures of LncRNAs and mRNAs in the myocardial tissue after RIPC. Therafter, homology comparisons were used to screen homologous genes from differentially expressed LncRNAs. Competing endogenous RNA (ceRNA) mechanism analysis were employed to find the matching relationship among homologous LncRNA, mRNA and microRNA. 554 differentially expressed mouse LncRNAs (281 up-regulated/273 down-regulated) and 1392 differentially expresssed human LncRNAs (635 up-regulated/757 down-regulated) were selected for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify these LncRNAs, homology comparison and ceRNA mechanism analysis provided a pair of homologous LncRNAs (ENST00000574727 & ENSMUST00000123752) for further research investigation. Overall, in this study, a number of differentially expressed LncRNAs were identified which may play an important role the regulation of both inflammation and cell proliferation. The findings may thus unveil the mystery of RIPC and discover a novel protective mechanism for the mitigation of cardiovascular ischemia-reperfusion disease.