A study of hemodynamic effects, postoperative recovery, and safety of esketamine (right handed) during flexible bronchoscopy under general anesthesia.

OBJECTIVE: Flexible bronchoscopy during general anesthesia has become an indispensable tool. Anesthetics are widely utilized in flexible bronchoscopy (FB). This study delved into the application value of a subanesthetic dose of esketamine (ES) (right handed) in flexible bronchoscopy during general anesthesia. METHODS: A sample of 160 patients who underwent flexible bronchoscopy during general anesthesia were selected as study subjects and were equally divided into the control and ES groups, with clinical baseline data (age, sex, body mass index, American Society of Anesthesiologists grading) collected. Hemodynamic parameters (mean artery pressure, heart rate, pulse blood oxygen saturation) at different time points, the onset time of anesthesia, surgery time, analgesia maintenance time, anesthesia awakening time, and perioperative adverse reactions were recorded. Visual analogue scale (VAS), Mini-Mental State Examination (MMSE), and quality of recovery-40 (QoR-40) scales were utilized for assessing post-surgery satisfaction, cognitive function, and post-surgery early recovery quality. RESULTS: The hemodynamics were stable at each time point, but patients in the ES group were more stable than those in the control group. Patients in the ES group exhibited faster onset and awakening time of anesthesia, longer duration of analgesia, and lower total incidence of adverse reactions versus the control group. The patients' QoR-40 total scores in the ES group were improved versus the control group at 1 day after surgery. CONCLUSION: Compared with fentanyl, the use of ES (right handed) in flexible bronchoscopy during general anesthesia produces more stable hemodynamics, faster onset and recovery time of anesthesia, longer duration of analgesia, lower incidence of adverse reactions, and improved early postoperative recovery quality in patients.

Chinese herbal decoction, Yi-Qi-Jian-Pi formula exerts anti-hepatic fibrosis effects in mouse models of CCl4-induced liver fibrosis.

Background: Yi-Qi-Jian-Pi Formula (YQJPF) is a herbal medicine that is used to treat patients with liver failure. However, scientific evidence supporting the treatment of hepatic fibrosis with YQJPF has not been forthcoming. The present study aimed to determine the mechanisms underlying the anti-fibrotic effects of YQJPF in mouse models of hepatic fibrosis. Methods: Mice were randomly assigned to control, hepatic fibrosis model, silymarin (positive treated), and low-, medium- and high-dose YQJPF (7.5, 15, and 30 g/kg, respectively) groups. Liver function, inflammatory cytokines, and oxygen stress were analyzed using ELISA kits. Sections were histopathologically stained with hematoxylin-eosin, Masson trichrome, and Sirius red. Macrophage polarization was measured by flow cytometry and immunofluorescence. Potential targets of YQJPF against hepatic fibrosis were analyzed by network pharmacology of Chinese herbal compound and the effects of YQJPF on the transforming growth factor-beta (TGF-ß)/Suppressor of Mothers against Decapentaplegic family member 3 (Smad3) signaling pathway were assessed using qRT-PCR and immunohistochemical staining. Finally, metagenomics and LC-MS/MS were used to detect the intestinal flora and metabolites of the mice, and an in-depth correlation analysis was performed by spearman correlation analysis. The data were compared by one-way ANOVA and least significant differences (LSDs) or ANOVA-Dunnett's T3 method used when no homogeneity was detected. Results: We induced hepatic fibrosis using CCl4 to establish mouse models and found that YQJPF dose-dependently increased body weight, improved liver function, and reversed hepatic fibrosis. Elevated levels of the pro-inflammatory factors IL-1ß, IL-6, and TNF-α in the model mice were substantially decreased by YQJPF, particularly at the highest dose. Levels of serum malondialdehyde and superoxide dismutase (SOD) activity were elevated and reduced, respectively. The malondialdehyde concentration decreased and SOD activity increased in the high-dose group. M1 polarized macrophages (CD86) in the mouse models were significantly decreased and M2 polarization was mildly decreased without significance. However, high-dose YQJPF increased the numbers of M2 macrophages and inhibited TGF-ß/Smad3 signaling. Metagenomic and non-targeted metabolomics detection results showed that YQJPF could regulate intestinal homeostasis, and Spearman correlation analysis showed that the abundance of Calditerrivibrio_nitroreducens was significantly negatively correlated with 18ß-glycyrrhetinic acid. It is suggested that Calditerrivibrio_nitroreducens may reduce the anti-fibrosis effect of licorice and other Chinese herbs by digesting 18ß-glycyrrhetinic acid. Conclusions: YQJPF can reverse liver fibrosis by inhibiting inflammation, suppressing oxidative stress, regulating the immunological response initiated by macrophages, inhibiting TGF-ß/Smad3 signaling and regulating intestinal flora homeostasis. Therefore, YQJPF may be included in clinical regimens to treat hepatic fibrosis.

Co-expression of IL-7 and PH20 promote anti-GPC3 CAR-T tumour suppressor activity in vivo and in vitro.

BACKGROUND: While CAR-T therapy has successfully treated haematological malignancies, it has proved sub-optimal for solid tumours. The main limitation is the inability of CAR-T cells to infiltrate and then proliferate within tumours. METHOD: We co-expressed IL-7 and PH20, a type of hyaluronidase, with CAR targeting GPC3 (G3CAR-7 × 20). We test the anti-tumour ability in vitro and in vivo. Moreover the capacity of infiltration and proliferation of G3CAR-7 × 20 was measured. RESULT: We found (G3CAR-7 × 20) exhibited better proliferation in vivo and in vitro than G3CAR, reduced the level of apoptosis after stimulation by tumour cells, and maintained the memory phenotype of CAR-T cells. G3CAR-7 × 20 also increased the ability of CAR-T cells to infiltrate tumour tissue. CONCLUSION: co-expressed IL-7 and PH20 may significantly enhance the efficacy of targeted GPC3 CAR-T cells in solid tumours treatment.

circRNA 001306 enhances hepatocellular carcinoma growth by up-regulating CDK16 expression via sponging miR-584-5p.

Circular RNAs (circRNAs) have been demonstrated to play important roles in cancer progress. However, the roles in hepatocellular carcinoma (HCC) are still unclear. Here, we found has_circRNA_001306 (circ_1306) was up-regulated in HCC tissues and cell lines. Knockdown the expression circ_1306 significantly suppressed HCC cell proliferation and induced the cell apoptosis in vitro and in vivo. Furthermore, we identified circ_1306 could up-regulate the expression of CDK16 by sponging miR-584-5p. The expression of miR-584-5p was decreased, and the expression of CDK16 was increased in HCC tissues and cell lines. Meanwhile, either knockdown of miR-584-5p or overexpression of CDK16 could suppress the HCC cell proliferation. In vivo, overexpression of miR-584-5p or knockdown of circ_1306 could inhibit the expression of CDK16, and suppress tumour growth. Altogether, our findings suggested that circ_1306 could promoter HCC progress by miR-584-5p/CDK16 axis, which provided a novel marker for HCC diagnosis and treatment.

Abnormally expressed lncRNAs in the prognosis and clinicopathology of oesophageal cancer: a systematic review and meta-analysis.

The relationship between the long noncoding RNA (lncRNA) expression and oesophageal cancer prognosis has been widely studied, but less consensus has been reached. We conducted this study to evaluate the relationship between the expression of lncRNAs and the prognosis and clinical pathology of oesophageal cancer. We conducted a systematic search of PubMed, EMBASE and Cochrane Library until 25 January 2019. Studies that evaluated the associations of a specific lncRNA with survival and/or clinicopathology of oesophageal cancer were included. Pooled hazard ratios (HRs), odds ratios (ORs), and corresponding 95% confidence intervals (CIs) were calculated using fixed or random-effect models. Sensitivity analysis was used to verify the stability of results. Publication bias was detected usingBegg tests and adjusted utilizing the trim-and-fill method if a bias existed. A total of 51 studies comprising 6510 patients and regarding 41 lncRNAs were included in the present systematic review and meta-analysis. The results showed that dysregulation of lncRNAs was associated with overall survival, disease-free survival, and progression-free survival. The expression of lncRNAs was related to some certain clinicopathological parameters of oesophageal cancer, including tumour size, T classification, lymph node metastasis, tumour node metastasis (TNM) stage and differentiation. Among these findings, lncRNA AK001796, CASC9, HOTAIR, MALAT1 and UCA1 were identified and were expected to be ideal biomarkers for the prognosis and clinicopathology of oesophageal cancer. Although significant publication bias was observed in some studies, the results were not changed after adjustment using the trim-and-fill method. Abnormal lncRNA-expression profiles could serve as a promising indicator for prognostic evaluation of patients with oesophageal cancer. The combination of these lncRNAs will contribute to clinical decision-making in the future.

Artesunate enhances γδ T-cell-mediated antitumor activity through augmenting γδ T-cell function and reversing immune escape of HepG2 cells.

OBJECTIVE: To explore the effect and mechanism of artesunate on γδ T cell-mediated antitumor immune responses against hepatoma carcinoma cells (HepG2) in vitro. METHODS: Human γδ T cells or HepG2 were respectively treated with artesunate, subjected to co-culture as appropriate, and the following assays were subsequently conducted: CCK8 to examine cell viability; LDH release assay to detect the killing effect of γδ T cells on HepG2 cells; flow cytometry to examine the expression of perforin (PFP) and granzyme B (GraB) of γδ T cells; ELISA to evaluate the levels of TGF-ß1 and IL-10 in the collected supernatant of HepG2 cells pretreated with artesunate; and Western blot analysis to examine Fas, FasL, STAT3, p-STAT3 expression of HepG2 cells induced by artesunate. Results: The results showed that the cytotoxicity effect of γδ T cells pretreated with artesunate on HepG2 cells was augmented via elevating the expression of GraB in γδ T cells. Furthermore, treatment with artesunate reversed the inhibition of HepG2 cells on γδ T cells by reducing the secretion of TGF-ß1 in HepG2 cells supernatant and enhanced the antitumor effect of γδ T cells against HepG2 cells through increasing the expression of Fas on HepG2 cells, which may be attributed to the inhibition of STAT3 signaling protein. CONCLUSION: Artesunate has several mechanisms for augmenting the antitumor immune responses mediated by γδ T cells. These results suggested artesunate may be an efficacious agent in the treatment of hepatocellular carcinoma.