[Characteristics and Prognosis in Adult Patients with Early T-Cell Precursor Acute Lymphoblastic Leukemia/Lymphoma from Multicenter].

OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of adult patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL). METHODS: Clinical data of 113 T lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients from January 2006 to January 2019 were collected from three hematology research centers, including Peking University Third Hospital, the First Medical Center of Chinese PLA General Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Medical University. The clinical characteristics and prognosis of ETP-ALL/LBL patients were analyzed compared with non-ETP-ALL/LBL patients. RESULTS: In 113 T-ALL/LBL patients, 13 cases (11.5%) were diagnosed as ETP-ALL/LBL, including 11 males, with a median age of 28(18-53) years. Compared with non-ETP-ALL/LBL patients, there were no significant differences in age, sex, incidence of large mediastinal mass, clinical stage, international prognostic index (IPI) score, white blood cell (WBC) count and lactate dehydrogenase (LDH) level among ETP-ALL/LBL patients. Among 13 ETP-ALL/LBL patients, 9 cases (69.2%) achieved complete remission (CR), and there was no statistically significant difference in response rate induced by chemotherapy between ETP-ALL/LBL patients and non-ETP-ALL/LBL patients. Among patients who received chemotherapy without allogeneic hematopoietic stem cell transplantation (allo-HSCT), ETP-ALL/LBL group had a worse 5-year overall survival (OS) rate compared with non-ETP-ALL/LBL group (0 vs 7.1%, P =0.008), while in patients with allo-HSCT, there was no significant difference for 5-year OS rate between the two group (37.5% vs 40.2%, P >0.05). Multivariate Cox regression analysis showed that CR after induction therapy, allo-HSCT, and LDH level were independent prognostic factors affecting T-ALL/LBL patients. CONCLUSION: No significant difference in response rate induced by chemotherapy is observed between ETP-ALL/LBL and non-ETP-ALL/LBL patients. Allo-HSCT consolidation after induction of remission therapy may have significant favorable influence on OS for patients with ETP-ALL/LBL.

PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers.

BACKGROUND: Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration in BTCs is unknown. This study aimed to determine the association between CD8+ T lymphocyte infiltration and the tumor microbiome in patients with resected BTCs. METHODS: Archived formalin-fixed paraffin-embedded tumor specimens were collected from patients with resected BTCs and analyzed using 16S rRNA gene sequencing to identify that prognosis-related and significantly differentially enriched taxa. Gene ontology (GO) analysis of the differentially enriched taxa was used to assess how CD8+ T lymphocyte infiltration is affected by the tumor microbiome of BTCs. RESULTS: We enrolled 32 patients with resected BTCs. The high CD8+ lymphocyte-infiltration (CD8hi) group had four significantly enriched taxa, and in the low CD8+ lymphocyte-infiltration (CD8low) group comprised one significantly enriched taxon. Patients with higher Clostridia abundance (enriched in the CD8hi group) experienced longer overall survival than those with lower abundance. The enrichment of Clostridia in the CD8hi group corresponded with lower CCL2 expression and downregulation of phosphatidylinositol 3-kinase activity, which might decrease myeloid-derived suppressor cell recruitment to the tumor milieu, thus increasing CD8+ lymphocyte infiltration in BTCs. CONCLUSIONS: The tumor microbiome is related to CD8+ T lymphocyte infiltration in patients with resected BTCs. The relationship between tumor Clostridia and high infiltration of CD8+ T lymphocytes might reflect decreased recruitment of myeloid-derived suppressor cells via the PI3K-CCL2-CCR2 axis.

Roles of HNO x and Carboxylic Acids in the Thermal Stability of Nitroplasticizer.

In the thermal aging of nitroplasticizer (NP), the produced nitrous acid (HONO) can decompose into reactive nitro-oxide species and nitric acid (HNO3). These volatile species are prone to cause cascaded deterioration of NP and give rise to various acidic constituents. To gain insight on the early stage of NP degradation, an adequate method for measuring changes in the concentrations of HONO, HNO3, and related acidic species is imperative. The typical assessment of acidity in nonaqueous solutions (i.e., acid number) cannot differentiate acidic species and thus presents difficulty in the measurement of HONO and HNO3 at a micromolar concentration level. Using liquid-liquid extraction and ion chromatography (IC), we developed a fast and unambiguous analytical method to accurately determine the concentration of HONO, HNO3, acetic/formic acids, and oxalic acid in aged NP samples. Given by the overlay analysis results of liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and IC, the prominent increase of produced HONO after the depletion of antioxidants is the primary cause of HNO3 formation in the late stage of NP degradation, which results in the acid-catalyzed hydrolysis of NP into 2,2-dinitropropanol and acetic/formic acids. Our study has demonstrated that the aging temperature plays a crucial role in accelerating the formation and decomposition of HONO, which consequently increases the acidity of aged NP samples and hence accelerates the hydrolyzation of NP. Therefore, to prevent NP from undergoing rapid degradation, we suggest that the concentration of HNO3 should be maintained below 1.35 mM and the temperature under 38 °C.

Tanshinone IIA - loaded pellets developed for angina chronotherapy: Deconvolution-based formulation design and optimization, pharmacokinetic and pharmacodynamic evaluation.

This paper put forward a deconvolution-based method for designing and optimizing tanshinone IIA sustained-release pellets (TA-SRPs) with improved efficacy in the treatment of variant angina. TA-SRPs were prepared by coating TA ternary solid dispersion immediate-release pellets (TA-tSD-IRPs) with the blends of polyvinyl acetate (PVAc) and polyvinyl alcohol-polyethylene glycol (PVA-PEG) using fluidized bed technology. The plasma concentration-time curve of TA-tSD-IRPs following oral administration as a weight function was investigated in New Zealand white rabbits. The predicted/expected plasma concentration-time curve of TA-SRPs as a response function was simulated according to the circadian rhythm of variant angina during 24h based on chronotherapy theory. The desired drug release profile of TA-SRPs was obtained via the point-area deconvolution procedure using the weight function and response function, and used for formulation optimization of TA-SRPs. The coating formulation of TA-SRPs was optimized as 70:30 (w/w) PVAc/PVA-PEG with 5% (w/w) coating weight due to in vitro drug release profile of these TA-SRPs was similar to the desired release profile (similarity factor f2=64.90). Pharmacokinetic studies of these optimized TA-SRPs validated that their actual plasma concentration-time curve possessed a basically consistent trend with the predicted plasma concentration-time curve and the absolute percent errors (%PE) of concentrations in 8-12h were less than 10%. Pharmacodynamic studies further demonstrated that these TA-SRPs had stable and improved efficacy with almost simultaneous drug concentration-efficacy. In conclusion, deconvolution could be employed in the development of TA-SRPs for angina chronotherapy with simultaneous drug efficacy and reduced design blindness and complexity.

Using stable isotopes to assess dietary changes of American black bears from 1980 to 2001.

We measured stable carbon and nitrogen isotope ratios in 117 hair samples from American black bears (Ursus americanus) in Great Smoky Mountains National Park, Tennessee, during 1980-2001 from live-trapped bears. We also collected hair from bears with known diets to compare with the wild bears. We hypothesized that biological factors (age, mass, and sex), food availability (hard mast and wild hogs (Sus scrofa)), and nuisance status would influence food selection by black bears and changes in their feeding history would be measureable using stable isotopes. We developed a set of a priori models using nine variables to examine changes in black bear stable isotope values. We found no support for changes in δ(13)C values associated with any of the nine variables we analyzed. Bears had enriched (15)N in years with low white oak mast production and depleted (15)N when white oak mast was abundant. Subadults had enriched (15)N compared with adults and older adults. Variation in δ(15)N increased from 1980-1991 to 1992-2000 when hard mast production had greater fluctuations. Bears in a better physical condition appeared more likely to access foods with higher protein content. In years of low white oak acorn production, larger bears and subadults likely turned to alternative food sources. The long-term variation detected in this study was important in identifying which bears were potentially more susceptible to changes in availability of hard mast.

[Case-control study on minimally invasive percutaneous new plate osteosynthesis applied in proximal humerus fractures in elder patients].

OBJECTIVE: To evaluate the clinical significance of minimally invasive percutaneous new plate osteosynthesis (MIPPO) applied in three and four-part fractures of proximal humerus in elder patients. METHODS: From June 2008 to December 2010, 98 old patients with three and four-part fractures of proximal humerus were treated with locking plate osteosynthesis. There were 43 males and 55 females with an average age of (71.3 +/- 6.2) years ranging from 65 to 84. Among them,47 cases were treated with minimally invasive percutaneous new plate osteosynthesis (MIPPO) through antrolateral transdeoltoid approach, and meanwhile 51 cases were treated with open reduction and internal fixation (ORIF) through a traditional deltopectoral approach. The operation time,blood loss,wound complications and hospital stay were recorded. The functional outcomes of the shoulder were assessed according to Constant score. RESULTS: Ninety-six patients were followed up for 13 to 42 months (averaged 18.1 months),and 2 patients died during the follow-up period. The mean blood loss of the MIPPO group was lower than that of the ORIF group by 125 ml (P < 0.05). There was no difference in the operation time between two groups. But the MIPPO group had a slightly shorter hospital stay than the ORIF group (P < 0.05). All the fractures united clinically and radiologically. The difference of the mean healing time between two groups was not significant. The mean Constant score at final follow-up of two groups had no statistic difference. But the rate of complication of the MIPPO group was lower than that of the ORIF group (P < 0.05). Only 1 case of the MIPPO group had axillary nerve paralysis post-operatively, but 4 cases had slack internal fixation and 2 cases had avascular necrosis of the humeral head in the ORIF group. CONCLUSION: The technique of percutaneous insertion combined new locking plate internal fixation has the advantages of less blood loss, rapid recovery, less vascular damage, lower risk of complications and so on. It can effectively treat the proximal humerus three-and four-part fractures, especially to elder patients with osteoporosis.

An evaluation of alumina reaction tube conditioning for high-precision 2H/1H isotope measurements via gas chromatography/thermal conversion/isotope ratio mass spectrometry.

RATIONALE: The condition of the pyrolysis reactor is very important for obtaining stable, precise hydrogen isotopic ratios using gas chromatography/thermal conversion/isotope ratio mass spectrometry (GC/TC/IRMS). However, few studies of the conditioning process have been conducted, and little is known about the best methods for high-precision hydrogen isotope analysis. METHODS: We investigated δ(2)H variations and observed the changes in carbon coating using six different conditioning methods for the pyrolysis alumina tube: (i) no treatment; (ii) conditioning with 4 µL hexane; (iii) conditioning with 2 µL hexane; (iv) conditioning with 2 µL hexane followed by backflushing overnight; (v) conditioning with 10 s of backflushing with methane; (vi) conditioning with 3 s of backflushing with methane. RESULTS: Conditioning the alumina tube can improve the pyrolysis efficiency of organic compounds because a moderate amount of carbon acts as a catalyst in high-temperature regions of the alumina tube. Carbon actually flows in the tube and is difficult to confine to the high-temperature region. Insufficient amounts of carbon in the high-temperature regions lead to incomplete pyrolysis of organic compounds and lower δ(2)H values due to kinetic fractionation of hydrogen isotopes. In contrast, excess hexane or methane can lead to higher δ(2)H values, probably due to enrichment of deuterium in the hydrocarbon residue. CONCLUSIONS: The δ(2)H values obtained by Method 6 are closest to the TC/EA δ(2)H values and are more precise than those obtained by other methods, perhaps because this method introduces a moderate, consistent amount of carbon with each sample injection.

Probiotic properties of lactic acid bacteria isolated from stool samples of longevous people in regions of Hotan, Xinjiang and Bama, Guangxi, China.

A total of 567 lactic acid bacteria (LAB) strains were isolated from the stool samples of longevous people in regions of Hotan, Xinjiang and Bama, Guangxi, China. In order to reduce the number of strains for further examinations, 36 isolates were screened out for further examination whilst the other strains, which had lower probiotic properties, were not suitable for yogurt production due to the absence of growth in pH 3.5 MRS medium and no curding during fermentation, and so were excluded. The result of identification by API, sequence analysis of 16S rRNA and random amplified polymorphic DNA (RAPD) analysis showed that there were three strains of Lactobacillus acidophilus, 10 strains of Lactobacillus rhamnosus, three strains of Lactobacillus casein, three strains of Lactobacillus brevis, two strains of Enterococcus faecium, two strains of Enterococcus faecalis, four strains of Bifdibacterium infantis, three strains of Bifdibacterium brevise, three strains of Bifdibacterium bifidium, two strains of Bifdibacterium adolecentis and one strain of Bifdibacterium longam among the 36 isolates. These strains were evaluated by in vitro methods including survival upon exposure to pH 2.0, 3.0 and/or 0.3% oxgall and adhesion to the human colon adenocarcinoma cell line Caco-2 as well as antimicrobial activity against potential pathogens. The results presented here show that L. rhamnosus LV108, L. rhamnosus F, B. brevise R39 and B. infantis R42 are acid and bile tolerant, adhere to the cultured human intestinal Caco-2 cell line, antagonistic activity against potential pathogenic bacteria infection in vitro, and so are potential strains for probiotic use.