[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

miR-499A>G rs3746444 and miR-146aG>C expression and hepatocellular carcinoma risk in the Chinese population.

We conducted a case-control study of a possible association of miR-499A>G rs3746444 and miR-146aG>C rs2910164 with risk of hepatocellular carcinoma. Samples from 172 hepatocellular carcinoma patients and 185 cancer-free controls were collected from October 2008 to December 2011. PCR-RFLP analysis was performed to determine the polymorphisms in each individual. The MAFs of miR-146aG>C and miR-499A>G in controls were similar to that known from the SNP database, and frequencies of genotypes in controls were in line with Hardy-Weinberg equilibrium. We found that miR-499 AG was significantly associated with decreased risk for hepatocellular carcinoma when compared with miR-499 AA genotype (adjusted odds ration = 0.74, 95% confidence interval = 0.24-0.96). However, subjects carrying miR-146a GG had a non-significant 0.62-fold decreased risk of hepatocellular carcinoma. We did not find a significant association of miR-146aG>C rs2910164 and miR-499A>G rs3746444 polymorphisms with hepatocellular carcinoma risk in the Chinese population. Further investigations are warranted to clarify the relationship between miRNA polymorphisms and susceptibility to hepatocellular carcinoma risk in various ethnic populations.

Antiviral effects on mouse leukemia virus replication by oligodeoxynucleotides in vitro and in vivo.

Oligodeoxynucleotides (Oligomers) including modified and unmodified, homo- and heterooligomers were tested for their ability to inhibit mouse SRS leukemia virus (SRSV)-induced proliferation of cells, colony formation, syncytium formation and reverse transcriptase (RT) activity in vitro. Phosphorothioate analogs complementary to Mo-MuLV sequences, as well as noncomplementary homooligomers, were found to be active. Unmodified homooligomer (dC14) also showed inhibition of growth of ascitic lymphoma carrying SRS virus. Our study suggests that different classes of oligonucleotides may inhibit SRSV replication with different mechanisms.

Effect of Astragulas membranaceus on natural killer cell activity and induction of alpha- and gamma-interferon in patients with Coxsackie B viral myocarditis.

The patients suffering from Coxsackie B viral myocarditis with depressed natural killer (NK) activity were treated with Astragulas membranaceus (AM) intramuscularly for 3-4 months. After the treatment, the NK activity was increased significantly from 11.5 +/- 11.9% before therapy to 44.9 +/- 15.0%. Another 6 patients of Coxsackie B viral myocarditis with depressed NK activity were treated with conventional therapy. The NK activity remained unchanged in 12.9 +/- 6%. The general condition and symptoms improved in all patients with AM therapy, while the titers of neutralizing antibody remained at the same level. Two days after AM treatment, the mean titers of alpha- and gamma-interferon (IFN) markedly increased in comparison with those before therapy and 3 weeks after AM therapy in 16 patients with Coxsackie B viral myocarditis, with left ventricular ejection fraction (LVEF) less than 65% and/or weak ventricular wall motion assayed by radionuclide angiocardiography. Whereas, in 12 patients treated with conventional therapy, there was no statistical difference among the results before and 2 days and 3 weeks after treatment. The results indicate that AM could partly regulate the lost of control of cellular immunity in patients with viral myocarditis.

[The findings of radionuclide angiocardiography in acute viral myocarditis].

Left ventricular function, both systolic and diastolic, was examined in 16 normal subjects and 62 patients of acute viral myocarditis with radionuclide angiocardiography. The results of patients as compared with those of normal showed that left ventricular ejection fraction, the peak ejection rate, the peak filling rate, the relative stroke volume and the relative cardiac output were lower (P less than 0.01 - 0.05). The phase angle from phase analysis was wider (P less than 0.01). Hypokinesia was noted by the observation of left ventricular wall motion 57 of 62 cases correlated well relative with the reduction left ventricular ejection fraction. Hypokinesia of left ventricular wall motion seems to be a more sensitive index than decrease of left ventricular ejection fraction for the diagnosis of acute viral myocarditis.

[Synthesis and antibacterial action of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroylthiocarbamoyl-1-piperaziny l)-3-quinoline carboxylic acids].

Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl-1-piperazinyl)-3- quinoline carboxylic acids were prepared. Their structures were characterized by elemental analysis, IR, HNMR and MS spectra. Preliminary pharmacological tests indicated that some of compounds Ia-m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 micrograms/ml.

Probing local conformational changes during equilibrium unfolding of firefly luciferase: fluorescence and circular dichroism studies of single tryptophan mutants.

Firefly luciferase is a monomeric protein composed of two globular domains. There is a wide cleft between the two domains. The N-terminal domain can be further divided into A-, B-, and C-subdomains. Previous studies showed that in vitro unfolding of firefly luciferase induced by guanidinium chloride can be described as a four-state equilibrium with two inactive intermediates (Herbst, R., et al. (1997) J. Biol. Chem. 272, 7099-7105). In order to monitor spectroscopically the conformational changes that occur in the different domains and subdomains during the multi-state unfolding process, we constructed a series of single-tryptophan mutants. These mutants were purified and characterized and shown to retain essentially all of the structural properties of the wild-type luciferase. Under equilibrium conditions, the unfolding of each mutant protein were studied by means of fluorescence and circular dichroism. The results show that different conformational changes occur in specific regions, suggesting a sequential unfolding process for firefly luciferase. Under 2.5 M GdmCl, whereas the N-domain unfolds partially holding half of the secondary structure content, the C-domain unfolds almost completely. In the equilibrium intermediate I(2), the secondary structure might stem mostly from the A- and B- subdomains.