Early on-treatment tumor growth rate (EOT-TGR) determines treatment outcomes of advanced non-small-cell lung cancer patients treated with programmed cell death protein 1 axis inhibitor.

BACKGROUND: Tumor growth rate (TGR), denoted as percentage change in tumor size per month, is a well-established indicator of tumor growth kinetics. The predictive value of early on-treatment TGR (EOT-TGR) for immunotherapy remains unclear. We sought to establish and validate the association of EOT-TGR with treatment outcomes in patients with advanced non-small-cell lung cancer (aNSCLC) undergoing anti-PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) therapy. PATIENTS AND METHODS: This bicenter retrospective cohort study included a training cohort, a contemporaneously treated internal validation cohort, and an external validation cohort. Computed tomography images were retrieved to calculate EOT-TGR, denoted as tumor burden change per month during a period between baseline and the first imaging evaluation after immunotherapy. Kaplan-Meier methodology and Cox regression analysis were conducted for survival analyses. RESULTS: In the pooled cohort (n = 172), 125 patients (72.7%) were males; median age at diagnosis was 58 (range 28-79) years. Based on the training cohort, we determined the optimal cut-off value for EOT-TGR as 10.4%/month. Higher EOT-TGR was significantly associated with inferior overall survival [OS; hazard ratio (HR) 2.93, 95% confidence interval (CI) 1.47-5.83; P = 0.002], worse progression-free survival (PFS; HR 2.44, 95% CI 1.46-4.08; P = 0.001), and lower objective response rate (3.3% versus 20.9%; P = 0.040) and durable clinical benefit rate (6.7% versus 41.9%; P = 0.001). Results were reproducible in the two validation cohorts for OS and PFS. Among 43 patients who had a best response of progressive disease in the training cohort, those with high EOT-TGR had worse OS (HR 2.64; P = 0.041) and were more likely to progress due to target lesions at the first tumor evaluation (85.2% versus 0.0%; P <0.001). CONCLUSIONS: Higher EOT-TGR was associated with inferior OS and immunotherapeutic response in patients with aNSCLC undergoing anti-PD-1/PD-L1 therapy. This easy-to-calculate radiologic biomarker may help evaluate the abilities of immunotherapy to prolong survival and assist in tailoring patients' management. TRIAL REGISTRATION: ClinicalTrials.govNCT04722406; https://clinicaltrials.gov/ct2/show/NCT04722406.

[Binding characteristics of chemosynthetic Ac-SDKP analogue FAM-Aca-SDKP to hepatic stellate cell-T6 cells].

OBJECTIVE: To investigate the binding of the chemosynthetic analogue of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) FAM-Aca-SDKP to hepatic stellate cell-T6 (HSC-T6) cells and basic physical characteristics. METHODS: The Ac-SDKP analogue short-peptide FAM-Aca-SDKP carrying green fluorescence was synthesized chemically. Quantitative real-time PCR was used to evaluate its effect on the secretion of HSC collagen and verify the consistency in the biological effect between FAM-Aca-SDKP and Ac-SDKP. A fluorescence microscope was used to observe the binding between FAM-Aca-SDKP and HSC-T6, and flow cytometry was used to evaluate the time-concentration effect of the binding between FAM-Aca-SDKP and HSC-T6. The t-test or rank sum test was used for the statistical analysis of different types of data. RESULTS: After HSC-T6 was incubated with Ac-SDKP or FAM-Aca-SDKP for 24 hours, the expression of type I collagen in HSC-T6 was increased, when the action time was 0.5 hour, Ac-SDKP and FAM-Aca-SDKP caused a 30%-50% reduction in the expression of type I collagen. After HSC-T6 was incubated with FAM-Aca-SDKP, strong green fluorescence was observed on cell surface under a fluorescence microscope, and after Ac-SDKP was added, Ac-SDKP significantly reduced the fluorescence intensity on cell surface due to competitive inhibition. Flow cytometry showed that when the concentration of FAM-Aca-SDKP was 0-50µmol/L, the rate of fluorescence-positive cells rapidly increased from 0 to 12%; when the concentration was 50-100µmol/L, the rate of fluorescence-positive cells only increased from 12% to 14%; co-incubation with Ac-SDKP significantly reduced the rate of fluorescence-positive cells. The number of positive cells reached the peak at the 45-minute point of the incubation and then decreased gradually. CONCLUSIONS: FAM-Aca-SDKP can bind to the surface of HSC-T6 cells, and this process has ligand-receptor binding characteristics such as competitive inhibition, saturability, and time-concentration effect.

[Evaluation of the effect of Nasopore on nasal packing in functional endoscopic sinus surgery].

Objective:To investigate the effect of Nasopore on nasal packing in functional endoscopic sinus surgery.Method:A total of 117 chronic rhinosiunsitis with or without nasal polyps patients undergone bilateral functional endoscopic sinus surgery and finished follow up visit were recruited. In accordance with various nasal packing materials in operation, patients were divided into Nasopore group, Sorbalgon group, Merocel group and Sorbalgon combined Mercel group. The VAS score was measured and differences were observed in patients of four groups in terms of subjective symptoms,post-operation adverse reaction and recovery of mucosa of operative nasal cavity in 2,4,8 and 12 weeks.Result:①The postoperative VAS symptoms score regarding nasal obstruction, nasal pain, head pressure feeling and discomfort in removal of the nasal packing in Nasopore group were significantly better than those in the other groups(P<0.05).②In Nasopore group,incidences of adverse reactions in epiphora, dysphagia, bleeding after removal nasal packing,surrounding mucosa scratches, nasal packing incarceration were significantly lower than that in the other groups(P<0.05). The incidences of fever,sneezing,bleeding in operation day and faint when removing nasal packing in four groups had no statistical differences(P> 0.05).③The postoperative Lund-Kennedy endoscopic mucosa morphology score in 2,4,8 and 12 weeks in four groups had no statistical differences(P> 0.05), and in each group the score was significantly lower as time changes(P<0.05).Conclusion:The Nasopore packing has definite hemostatic efficacy,little postoperative discomfort and nice mucosal healing outcome as well in patients after functional endoscopic sinus surgery.It indicates that Nasopore is an effective and reliable packing material in FESS.

Octanoylated Ghrelin Inhibits the Activation of the Palmitic Acid-Induced TLR4/NF-κB Signaling Pathway in THP-1 Macrophages.

To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages, THP-1 macrophages were cultured for 12 h by palmitic acid with various concentrations. The THP-1 macrophages was pretreated by acylated ghrelin at different doses for 4 h before cultivated by palmitic acid (200 µmol/L) for 12 h. We observed the level of TLR4, NF-κB p65 phosphorylation in THP-1 macrophages and TNF-α, IL-1ß in culture supernatant. TLR4 mRNA was measured by real-time PCR. TLR4 protein and NF-κB p65 phosphorylation was measured by western blotting. The expression of TNF-α and IL-1ß was detected by ELISA. Compared to the THP-1 macrophages without palmitic acid, the level of TLR4 mRNA protein and NF-κB p65 phosphorylation and the expression of TNF-α and IL-1ß increased after treatment by palmitic acid in a dose-dependent fashion (P < 0.05). Compared to the THP-1 macrophages with palmitic acid (200 µmol/L), the level of the pervious substances decreased after preadministration by acylated ghrelin in a dose-dependent fashion. So, we make a conclusion that acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1 macrophages which are stimulated by palmitic acid in a dose-dependent fashion.

Genomewide linkage scan for combined obesity phenotypes using principal component analysis.

Traditional whole genome linkage scans for obesity were usually performed for a number of correlated obesity related phenotypes separately without considering their correlations. The purpose of this study was to identify quantitative trait loci (QTLs) underlying variations in multiple correlated obesity phenotypes. We performed principal component analysis (PCA) for four highly correlated obesity phenotypes (body mass index [BMI], fat mass, percentage of fat mass [PFM], and lean mass) in a sample of 427 pedigrees (comprising 3,273 individuals) and generated two independent principal components (PC1 and PC2). A whole genome linkage scan (WGS) was then conducted for PC1 and PC2. For PC1, the strongest linkage signal was identified on chromosome 20p12 (LOD = 2.67). For PC2, two suggestive linkages were found on 5q35 (LOD = 2.03) and 7p22 (LOD = 2.18). This study provided evidence supporting several previously identified linkage regions for obesity (e.g., 1p36, 6p23 and 7q34). In addition, our approach by linear combination of highly correlated obesity phenotypes identified several novel QTLs which were not found in genome linkage scans for individual phenotypes.

[Protective effect of tanshinone on injured cultured PC12 cells in vitro].

OBJECTIVE: To investigate the protective effects of tanshinone on ischemia-like injury models. METHOD: Six ischemia models including hypoxia, hypoglucose, oxidant injury, calcium overload, nitric oxide neurotoxicity and glutamic acid injury were used to assay the anti-ischemic roles of tanshinone in cultured PC12 cells, by using morphological examination, MTT staining and LDH measurement. RESULT: It was found that 3. 125-200 microliters.ml-1 tanshinone possessed obvious protective effects on PC12 cells from six ischemia-like injury models. Tanshinone could increase the number of life cells and decrease LDH activity significantly, particularly in hypoxia and caffeine injured model. CONCLUSION: Tanshinone protected PC12 cells from all injury models effectively in vitro. Its action may mainly focus on inhibiting development of the primary period of ischemia injury and calcium overloading injury.

An outbreak of epidemic diarrhoea in adults caused by a new rotavirus in Anhui Province of China in the summer of 1983.

Shexian County of Anhui Province in East China experienced a severe outbreak of nonbacterial diarrhoea in May and June of 1983. Over 20,0000 cases were reported. Most were adults of 20 to 50 years old. The isolated virus was morphologically indistinguishable from ordinary infantile rotavirus, but CF and ELISA tests showed that the new virus lacked the common group-A antigen shared by ordinary rotavirus. Nine of 10 convalescent-phase and three paired sera of patients showed antibody positive, with a greater than four-fold antibody rise against new rotavirus in the CF test. Seventeen faecal samples from patients showed identical, and special, electropherotype. They all had a double-stranded RNA with 11 discrete segments. The RNA profiles were quite different from those of reference rotavirus Wa strain and ordinary infantile rotaviruses. Third and 4th segments were near to each other, 5th and 6th segments were very close, but 7th, 8th, and 9th segments were widely separated. This study indicates the new virus can be identified as part of a new group of rotaviruses. This new rotavirus has been incriminated as the causative agent of the epidemic.