How to Choose a Survival Period? The Impact of Antibiotic Use on OS or PFS in NSCLC Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: The development of immunotherapy has dramatically changed the treatment of non-small-cell lung cancer. The negative association of antibiotics on the clinical activity of immune checkpoint inhibitors in patients with NSCLC is well known. METHODS: PubMed, Embase, and Medline databases were searched until January 11, 2020. We included retrospective studies of ICIs (e.g., PD-1, PD-L1, and CTLA-4). The clinical outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed. RESULTS: Our results indicated that the use of antibiotics reduced the survival of NSCLC patients treated with ICIs. The pooled HRs of PFS and OS were HR = 1.41 (95% CI = 1.23-1.61; P < 0.001) and HR = 2.16 (95% CI = 1.79-2.60; P < 0.001). We divided the studies into 5 subgroups according to antibiotic exposure time. Subgroup analysis showed that the patients that were administered antibiotics [-60 days; 0 days] or [-30 days; 0 days] before the initiation of ICIs treatment had a poorer OS rate, whereas those patients that were administered antibiotics [0 days; 30 days] after the initiation of ICIs treatment had a poorer PFS rate. In summary, ATB treatment in patients [-60 days; +30 days] near the initiation of ICIs treatment significantly reduced the survival in NSCLC patients. CONCLUSION: Our results indicated that ATB use is negatively associated with survival in NSCLC patients treated with ICIs immunotherapy. Similar studies involving a larger sample of cases are still being published. This meta-analysis identified that the timing of ATB treatment in NSCLC patients receiving ICIs immunotherapy has different effects on the OS and PFS of these patients. ATB treatment prior to the initiation of ICIs treatment affects OS, whereas ATB treatment after the initiation of ICIs treatment affects PFS.

miR-1306-3p targets FBXL5 to promote metastasis of hepatocellular carcinoma through suppressing snail degradation.

This study aimed to elucidate the effect of miR-1306-3p on metastasis of hepatocellular carcinoma (HCC) and potential mechanism involved. miR-1306-3p promoted migration and invasion of HCC in vivo and in vitro. Moreover, miR-1306-3p inhibited snail to enhance its expression via directly targeting FBXL5, thus inducing the epithelial-mesenchymal transition (EMT) in HCC. Intriguingly, miR-1306-3p expression was transcriptionally enhanced by FoxM1. Consistently, miR-1306-3p was upregulated in HCC compared with paracarcinoma and correlated with poor prognosis of HCC patients. Our researches suggest that miR-1306-3p is a tumor enhancer in regulating of HCC metastasis, and miR-1306-3p may be clinically utilized as a factor for the clinical diagnosis and prognosis of HCC.

Efficient gene vector with size changeable and nucleus targeting in cancer therapy.

The nucleus is one of the most important cellular organelles, where gene encode and transcribe at that location. However, nucleus-targeting gene delivery are rare been reported. It is important to develop a high-efficiency nucleus-targeting gene vector that can deliver targeted gene into nucleus directly for destroy of cancer cells. Here, special nucleus-targeting and size changeable deliver system based on TAT-SS-PAMAM-D3 with TAT functional on the surface and disulfide linked between D2 and D3 is designed to perform highly efficient nucleus-targeting gene delivery for effective cancer cell killing in vitro. CLSM observations reveal that more TAT-SS-PAMAM-D3 are enter into the nucleus when compare to SS-PAMAM-D3. The TAT modified vector can also act as gene deliver to reach high gene transfection efficiencies, high apoptosis and low viability in HeLa cells. This TAT functionalized and disulfide linking in the carrier may become a prospective vector for cancer gene treatment and also offered a different strategy for designing a better gene delivery system.

[Influence of Activated Sludge Surface Properties on Flocculating Settling and Effluent Suspend Solid].

In this paper, the influence of the surface properties of the activated sludge on flocculating settling and ESS was studied in seven different sewage treatment plants in Beijing, such as the sludge volume index (SVI), the protein/carbohydrate (P/C) ratio in extracellular polymeric substance, Zeta potential, two-dimensional fractal dimension(D2f). The relationships between the surface properties of the activated sludge and flocculation ability (FA) or effluent suspend solid(ESS) were also analyzed. The results showed that no obvious correlation was obtained between SVI and FA or ESS, but obvious negative correlation between the FA and ESS (R2=0.787) was observed. When the P/C increased from 1.28 to 25.34, the FA could increase from 0.19 to 0.73 correspondingly, but the ESS decreased from 14.89 mg·L-1 to 6.08 mg·L-1. This was because the amino acids in protein with positive charge could neutralize the negative charge on the surface of floc, the increase of protein ratio in EPS could decrease the absolute value of Zeta potential, which made a contribution to form more stable floc structure, and improved the ability of flocculation. Moreover, the Zeta potential had a positive correlation with FA but a negative correlation with ESS. The absolute value of Zeta potential decreased by 1 mV, FA increased by 0.059 and ESS decreased by 0.934 mg·L-1 correspondingly. In addition, there was an obvious index correlation (R2=0.935, P<0.01) between D2f and FA; While D2f increased from 1.10 to 1.45, FA could increase by 4.3 times and ESS decreased linearly (R2=0.868).

[Establishment of animal model of myoclonus originating from axis of cortex-thalamus].

OBJECTIVE: To develop a series of experimental animal models of myoclonus with different origins consistent with myoclonus seizure in clinic setting. METHODS: GABA(A) antagonist SR95531 was microinjected into the primary motor cortex (PMC), corpus striatum, nucleus reticular of the thalamus (NRT) to induce myoclonus (EMG burst of myoclonus