[Treatment of oligoprogression to immunotherapy resistance in advanced non-small cell lung cancer].

In recent years, the incidence of lung cancer has been increasing year by year. Traditional treatments have limited clinical effects in advanced, driver-gene-negative non-small cell lung cancer. Immune checkpoint inhibitors (ICI) have dramatically changed the treatment landscape of advanced non-small cell lung cancer. However, most patients are suffered from primary and acquired resistance inevitably. Oligoprogression is one of the main progression patterns of acquired resistance. Therefore, it is essential to further understand treatment of oligoprogression to immunotherapy resistance. This article aimed to conduct a systematic review of the treatment of oligoprogression to immunotherapy resistance.

[Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy].

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

In silico identification of potential virulence genes in 1,3-propanediol producer Klebsiella pneumonia.

The pathogenic characteristics of Klebsiella pneumoniae could pose security risks for industrial applications. In this study, the existence and distribution of 2457 known virulence genes (VFs) in 9 strains of K. pneumoniae were systematically analyzed by high-throughput in silico methods. We found different numbers and types of VFs in 9 K. pneumoniae strains using database sequences. Some VFs in the database were highly homologous with the corresponding genes in K. pneumoniae genomes. Four large fragments with contiguous potential virulence genes named VF1, VF2, VF3 and VF4 were identified. VF1 and VF2 were found in all 9 sequenced strains and the 1,3-propanediol-producing strain KG1. When the VF2 fragment was knocked out in KG1, cell growth and 1,3-propanediol production in the mutant were nearly the same as in KG1. Consequently the resulting information by in silico methods is useful for identifying potential virulence genes of K. pneumoniae used for 1,3-propanediol production.

Utilization of excess NADH in 2,3-butanediol-deficient Klebsiella pneumoniae for 1,3-propanediol production.

AIMS: To utilize excess NADH for 1,3-propanediol production by 2,3-butanediol-deficient mutants, the effect of dhaT overexpression in two distinct 2,3-butanediol-deficient mutants was investigated. METHODS AND RESULTS: Two 2,3-butanediol-deficient mutants, KG1-3 (blocking of the 2,3-butanediol pathway only) and KG1-5 (blocking of both of 2,3-butanediol and lactate pathways) were constructed. Our results showed that although the intracellular redox balance (NADH/NAD(+)) was extremely high at the end of fermentation for both mutants, the status of intracellular redox in KG1-5 was maintained at a normal level following the first stage of fermentation. Analysis of cell growth and metabolite formation confirmed the inhibition of excess lactate in 2,3-butanediol pathway-deficient mutants. Furthermore, dhaT was overexpressed in two 2,3-butanediol-deficient mutants (KG1-3T and KG1-5T). In KG1-5T, the intracellular redox balance was restored to normal and 1,3-propanediol production increased. The yield of 1,3-propanediol from glycerol in KG1-5T was also restored to a normal level of 0·6. CONCLUSIONS: The excess NADH in both the 2,3-butanediol- and lactate-deficient mutants can be used by overexpresstion of dhaT. SIGNIFICANCE AND IMPACT OF STUDY: The metabolic flux tended to increase lactate production by the abolishment of the 2,3-butanediol pathway in Klebsiella pneumoniae, and the high accumulation of lactate prevented the cell from using excess NADH, thereby inhibiting cell growth and 1,3-propanediol production.

Levels of PCDD/Fs, Dl-PCBs and HCB in air, soils and sediments from a city with multiple thermal-related industries in China.

The levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs) and hexachlorobenzene (HCB) were measured in various environmental compartments in Tangshan, China, which contains multiple thermal-related industries. The total toxic equivalent concentrations of these pollutants were 138 ± 87.2 fg/m(3) in air, 3.43 ± 2.88 pg/g in soils, and 1.42 ± 1.5 pg/g in sediments. The 2,3,7,8-PCDD/Fs profiles in atmospheric samples suggest that thermal-related industries are the most likely potential sources. Of the dl-PCBs, CB-77, CB-105 and CB-118 were the most abundant congeners and CB-126 was the dominant contributor to the TEQs from the dl-PCBs.

Levels and profiles of unintentionally produced persistent organic pollutants in surface soils from Shanxi province, China.

Six species of unintentionally produced persistent organic pollutions comprised of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, polychlorinated biphenyls, polychlorinated naphthalenes, hexachlorobenzene and pentachlorobenzene in soils collected from Shanxi province, China were determined. The sum toxic equivalent ranged from 0.14 to 2.20 with an average of 0.94 pg TEQ/g. Polychlorinated dibenzo-p-dioxins/furans contributed the most toxic proportion to the total toxic equivalent. CB-126 was the most toxic contributor to polychlorinated biphenyls. CN66/67 and CN73 are the dominant toxic congeners to polychlorinated naphthalenes. From the patterns, it was speculated that thermal related industries were possible sources of unintentionally produced persistent organic pollutions.

Declining polychlorinated dibenzo-p-dioxins and dibenzofurans levels in the sediments from Dongting Lake in China.

Dongting Lake is the second largest freshwater lake in China. Technical sodium pentachlorophenate (Na-PCP) had been sprayed since 1960s to control the spread of snailborne schistosomiasis up to the middle of 1990s. As one of the by-products of Na-PCP, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) may enter the environment. It has been reported that the concentrations of PCDD/Fs in sediments in Dongting Lake were 130-891 pg I-TEQ g(-1) in 1995. High toxicity of sediment to exposed microorganisms and fish may be risk on environment. In order to determine the present levels of the contamination, eight sediment samples from Dongting Lake were analyzed for PCDD/Fs using HRGC-HRMS. Total I-TEQ values for these samples were at a ranged of 0.7-11 pg g(-1), with a mean value of 4.5 pg g(-1). The results show that PCDD/Fs concentrations of contemporary sediment have declined since 1995. Certain PCDD/F congeners as well as OCDD, typical for Na-PCP, predominated in lake sediment indicating that the using of PCP-Na is the main source of PCDD/Fs in the lake. These variations in levels can reflect changes in PCDD/F sources to the environment over time.

[Ameliorative effects of adrenomedullin on rat cardiac sarcoplasmic reticulum injured by isoproterenol].

Five indices were used to assess the degree of the ameliorative effects of adrenomedullin (Adm) in isoproterenol (ISO) induced injury of cardiac sarcoplasmic reticulum (SR) of rats: +/- LV dp/dtmax, SR Ca2+ uptake, Ca2+ release (in nmol/mg SR protein) and Ca(2+)-ATPase activity. Adm (5 x 10(-5) mol/L) was perfused into rat heart before cardiac function +/- LV dp/dtmax was determined. Cardiac SR was purified and SR Ca2+ uptake, Ca2+ release, Ca(2+)-ATPase activity, and 3H-ryanodine maximal binding (Bmax) were measured. After perfusion of Adm (5 x 10(-5) mol/L), the +LV dp/dtmax and -LV dp/dtmax in ISO injured heart were increased by 16.9% (2,135 +/- 281 vs 1980 +/- 302, P < 0.05) and 29.2% (1375 +/- 267 vs 1064 +/- 355, P < 0.05), respectively. Cardiac SR Ca2+ uptake and Ca2+ release were increased by 23.0% (15.0 +/- 1.4 vs 12.2 +/- 1.2, P < 0.01) and 43.5% (6.6 +/- 1.0 vs 4.6 +/- 0.6, P < 0.01), respectively. Ca(2+)-ATPase activity and 3H-ryanodine binding were increased by 23.0% (P < 0.01) and 42.2% (P < 0.05), respectively. It seems that Adm exerted a protective effect on cardiac function in injured rat heart by enhancing SR Ca2+ uptake and release, suggesting that Adm may play a therapeutic role in myocardial injury.

[Distribution of obese protein in the mouse tissue].

In the present study, the contents of obese protein of tissue from liver, brain, abdominal wall fat, skeletal muscle and the contents of plasma OP of mice were measured with radio immunoassay. The results showed that the contents of OP were much higher in the brain than that in the abdominal wall fat tissue (P < 0.01). The liver and the skeletal muscle tissue did not show the presence of OP. The contents of OP of abdominal wall fat tissue were lower in the female than that in the male mice (P < 0.05).

[L-arginine transport in cultured vascular smooth muscle cells of spontaneously hypertensive rats and effect of liposome on the transport].

The characteristics of L-arginine (L-Arg) transport in cultured aortic smooth muscle cells (SMC) of spontaneously hypertensive rat (SHR) and control WKY rats were studied and the effect of liposome as L-Arg carrier on the transport was investigated. The results showed that the L-Arg transport of SMC in SHR was obviously lower than that in WKY rats. Maximum transport velocity (Vmax) of high and low affinity in SHR were respectively 48% (P < 0.01) and 49% (P < 0.01) of WKY rat, while the michaelis constant (K(m)) showed no significant difference (P > 0.05). Increase of L-Arg transport induced by tumor necrosis factor-alpha (TNF alpha) in SMC of SHR was obviously lower than that in WKY rats (P < 0.01). The uptake of L-Arg increased 10 to 20 times in SMC when incubated with liposome encapsulated L-Arg (Liposome-L-Arg) than with free L-Arg. The transport velocity in SMC incubated with liposome-L-Arg showed no significant difference in SHR and WKY rats (P > 0.05). The transport of liposome-L-Arg in SMC was not affected by TNF alpha in both the types of rats. The above results indicate that there exists a functional disturbance in L-Arg transport in the SMC of SHR, but the L-Arg transport in SMC can be obviously enhanced when liposome is used as L-Arg carrier. Thus, it appears that liposome-L-Arg may have clinical perspective in the treatment of hypertension.