[Clinical and chest CT features of immune checkpoint inhibitor-related pneumonitis].

Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.

[Pretreatment evaluation of 18F-FDG PET-CT in extranodal NK/T-cell lymphoma].

Objective: To investigate the clinical value of pretreatment 18F-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET-CT) in extranodal NK/T-cell lymphoma. Methods: Eighty-one patients with pathologically confirmed extranodal NK/T-cell lymphoma and pretreatment with PET-CT scan in Cancer Hospital, Chinese Academy of Medical Sciences from August 2006 to December 2017 were enrolled in the study. The clinical, follow-up and imaging data were analyzed retrospectively. The relationship between maximum standard uptake value (SUVmax) and prognosis were evaluated by Mann-Whitney U test and Spearman rank correlation analysis. Results: Among the 81 patients, 98.8% (80/81) were upper aerodigestive tract (UAT) involved. Lesions at extra-UAT sites were detected in 7 cases, involving parotid gland (n=1), breast (n=1), spleen (n=1), pancreas (n=1), skin and subcutaneous soft tissue (n=1), muscle (n=1), lung (n=2) and bone (n=3). Lymph node involvement were demonstrated in 33 cases. All of the lesions had increased uptake of PET, the median SUVmax was 8.6. PET-CT changed staging in 15 cases, and 12 cases were adjusted treatment methods. 21 cases were changed radiotherapy target because of PET-CT. The 1-, 2-year progression-free survival (PFS) rates were 88.7% and 80.3% while 1-, 2-year overall survival (OS) rates were 97.2% and 94.4% respectively. The median SUVmax of patients with local lymph nodes involvement was significantly higher than those without local lymph nodes involvement (P=0.007). The SUVmax was positively associated with Ann Arbor stage (r=0.366, P=0.001), lactate dehydrogenase (r=0.308, P=0.005) and Ki-67 level (r=0.270, P=0.017). The SUVmax was inversely associated with lymphocyte count (r=-0.324, P=0.003) and hemoglobin content (r=-0.225, P=0.043). Conclusions: Extranodal NK/T-cell lymphoma predominantly occurs in extra-nodal organs, mainly in the upper respiratory and gastrointestinal tracts, with marked FDG-addiction. Compared with conventional imaging, 18F-FDG PET-CT is sensitive and comprehensive in detecting extra-nodal NK/T-cell lymphoma involvement, assisting in accurate clinical staging and treatment planning. Pretreatment SUVmax is potential for prognosis evaluation since it is correlated with prognostic factors.

[Potential value of FDG PET-CT in predicting occult lymph node metastasis in clinical stage â A lung adenocarcinoma].

Objective: To investigate the predictive value of (18)F-FDG PET-CT scan for occult lymph node metastasis in patients with stage ⅠA lung adenocarcinoma. Methods: The image and pathological data of 272 patients with stage ⅠA lung adenocarcinoma from October 2006 to September 2015 were retrospectively analyzed. All patients underwent preoperative (18)F-FDG PET-CT scan followed by lobectomy and systematic lymph node dissection. The correlation between occult lymph node metastasis and the maximum standardized uptake value (SUV(max)) of primary tumor as well as other clinicopathological factors was analyzed to screen the risk factors of occult lymph node metastasis in stage ⅠA lung adenocarcinoma. Results: Occult lymph node metastasis was detected in 50 patients (18.4%), with 24 (8.8%) patients of pN1 involvement and 26 (9.6%) of pN2 involvement. Among the 272 patients enrolled, 39 had pure ground glass nodule, 59 had part-solid nodule and 174 had solid nodule. All patients with pure ground glass nodule or nodule≤1 cm were pN0. For the 233 patients with part-solid and solid nodule, no lymph node metastasis was found in T1a stage (tumor length ≤1 cm). Primary tumor SUV(max) (Z=-5.663, P<0.001), nodule type (χ(2)=21.586, P<0.001), tumor location (χ(2)= 12.790, P< 0.001), histological grade (χ(2)= 22.784, P< 0.001) and visceral pleural invasion (χ(2)=5.357, P=0.021) showed significant differences between occult lymph node metastasis group (pN+ ) and non-lymph node metastasis group (pN0). With SUV(max)=2.405 as cut-off value, the sensitivity and specificity for predicting occult lymph node metastasis were 90.0% and 61.7%, the area under curve was 0.761(95%CI=0.700~0.823), and the negative predictive value was 95.8%. Multivariate analysis revealed that SUV(max) >2.405 (P<0.001), central location (P=0.030) and higher histological grade (P=0.024) were independent predictors of occult lymph node metastasis. Conclusions: For clinical stage ⅠA adenocarcinoma, primary tumor SUV(max) > 2.405, central location and higher histological grade were independent risk factors for occult lymph node metastasis. Systematic lymph node dissection may be avoided in lung adenocarcinoma with pure ground glass density, tumor length ≤1 cm or SUV(max) ≤ 2.405, due to the very low probability of nodal involvement.

Both genes and lncRNAs can be used as biomarkers of prostate cancer by using high throughput sequencing data.

OBJECTIVE: To investigate prostate cancer-related genes and lncRNAs by using a high throughput sequencing dataset. MATERIALS AND METHODS: RNA-seq data were obtained from the sequencing read archive database, including both benign and malignant tumor samples. After aligning the RNA-seq reads to human genome reference, gene expression profile as well as lncRNA expression profile was obtained. Next, student's t-test was used to screen both the differentially expressed genes (DEGs) and lncRNAs (DELs) between benign and malignant samples. Finally, goseq was used to conduct the functional annotation of DEGs. RESULTS: A total of 7112 DEGs were screened, such as ZNF512B, UCKL1, STMN3, GMEB2, and PTK6. The top 10 enriched functions of DEGs were mainly related to organism development, including multi-cellular development, system development and anatomical structure development. Also, we discovered 26 differentially expressed lncRNAs. CONCLUSIONS: The analysis used in this study is reliable in screening prostate cancer markers including both genes and lncRNAs by using RNA-seq data, which provides new insight into the understanding of molecular mechanism of prostate cancer.

Constitutive expression of Vitreoscilla haemoglobin in Sphingomonas elodea to improve gellan gum production.

AIMS: To improve a commercially used strain for gellan production by exogenous Vitreoscilla haemoglobin (VHb). METHODS AND RESULTS: VHb gene was expressed in Sphingomonas elodea under the control of constitutive bla promoter. Biochemical activity of expressed VHb was confirmed by CO-difference spectra analysis that exhibited a characteristic absorption maximum at 419 nm. During cultivation, not only enhanced cell growth was detected, but also 20% improvement in gellan production was observed after 48 h of incubation, with a maximum yield of 16·82 g l(-1). Moreover, maximum sucrose conversion efficiency (g gellan per g sucrose) was 57·8, 20% higher than that of the parental strain. We further examined the polysaccharide production of VHb-expressing strain at different aeration levels in Erlenmeyer flasks. Again, in all cases, a significant enhancement of gellan production was observed, and the enhancement was more significant under oxygen-limiting conditions (up to 26·8%). CONCLUSIONS: VHb exhibited positive effect on cell growth and gellan yield of S. elodea, especially under hypoxic conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first application of VHb as an effective metabolic engineering strategy in S. elodea to regulate cell growth and optimize gellan yield.

Analysis of the stability and degradation products of triptolide.

Triptolide is the major active ingredient of the Chinese herbal remedy Tripterygium wilfordii Hook F. (TwHF). As triptolide content is used to estimate the potency of preparations of TwHF, assessment of its stability is warranted. The accelerated stability of triptolide was investigated in 5% ethanol solution in a light-protected environment at pH 6.9, within a temperature range of 60-90 degrees C. The observed degradation rate followed first-order kinetics. The degradation rate constant (K25 degrees C) obtained by trending line analysis of Arrhenius plots of triptolide was 1.4125 x 10(-4) h(-1). The times to degrade 10% (t1/10) and 50% (t1/2) at 25 degrees C were 31 and 204 days, respectively. Stability tests of triptolide in different solvents and different pH conditions (pH4-10) in a light-protected environment at room temperature demonstrated that basic medium and a hydrophilic solvent were the major factors that accelerated the degradation of triptolide. Triptolide exhibited the fastest degradation rate at pH 10 and the slowest rate at pH 6. In a solvent comparison, triptolide was found to be very stable in chloroform. The stability of triptolide in organic polar solvents tested at both 100% and 90% concentration was greater in ethanol than in methanol than in dimethylsulphoxide. Stability was also greater in a mixture of solvent:pH6 buffer (9:1) than in 100% solvent alone. An exception was ethyl acetate, which is less polar than the other solvents tested, but permitted more rapid degradation of triptolide. Two of the degradation products of triptolide were isolated and identified by HPLC and mass spectroscopy as triptriolide and triptonide. This suggested that the decomposition of triptolide occurred at the C12 and C13 epoxy group and the C14 hydroxyl. The opening of the C12 and C13 epoxy is an irreversible reaction, but the reaction occurring on the C14 hydroxyl is reversible. These results show that the major degradation pathway of triptolide involves decomposition of the C12 and C13 epoxy group. Since this reaction is very slow at 4 degrees C at pH 6, stability is enhanced under these conditions.

A potential new treatment for rheumatoid arthritis: thunder god vine.

Various extracts of the vinelike plant Tripterygium wilfordii Hook f have been widely used in China to treat patients with a number of autoimmune diseases. Although most of the clinical experience has derived from uncontrolled trials, one placebo-controlled double-blind trial has clearly demonstrated efficacy in rheumatoid arthritis. Studies in laboratory animals have indicated that extracts of Tripterygium wilfordii Hook f suppress both immune and inflammatory responses and also effectively treat a number of models of autoimmune disease. More detailed in vitro analysis has indicated that components of Tripterygium wilfordii Hook f suppress immune responses by inhibiting transcription of cytokine genes, including interleukin-2 and gamma interferon. The current status of knowledge of the potential clinical benefit of this herbal remedy and possible mechanisms accounting for its utility are considered in this review.

A prospective, controlled, double-blind, cross-over study of tripterygium wilfodii hook F in treatment of rheumatoid arthritis.

A polyglycosides of Tripterygium wilfodii hook F (TWH) preparation with a code name of T2 is used in the present double-blind, controlled, cross-over study on the treatment of 70 cases of rheumatoid arthritis (RA). An impressive curative effect of T2 is confirmed much more convincingly by the present study than that by the previously reported clinical open trials. The adverse reactions and the probable pharmacological mechanism of T2 are also discussed.

[Mechanism of treating rheumatoid arthritis with Tripterygium wilfordii hook. II. Effect on PGE2 secretion].

PBMC from normal adults and patients with rheumatoid arthritis (RA) were cultured in the absence or presence of various concentrations of T2, indomethacin, dexamethasone for certain periods of time. The amounts of PGE2 in the cell-free supernatants were measured by radioimmunoassay, and a significant reduction of PGE2 production by PBMC cultured with 2-50 micrograms/ml of T2 was found. The percentages of inhibition of PGE2 production in the cultures with 2 micrograms/ml, 10 micrograms/ml and 50 micrograms/ml of T2 were 44.1 +/- 5.3%, 89.5 +/- 4.9% and 84.3 +/- 8.5% respectively. The PGE2 concentrations in the culture supernatants of RA PBMC were higher than those in the supernatants of normal PBMC, but the inhibitory effect of T2 on RA PBMC production of PGE2 was similar to that on normal PBMC. In comparison with indomethacin, the inhibitory effect of T2 on PGE2 production was less remarkable. However, T2 exhibits therapeutic effects on RA which are superior to any other non-steroid anti-inflammatory drug, suggesting that the inhibitory effect of T2 on PGE production may only be one of its therapeutic mechanisms in the treatment of patients with RA.

Human IgG aggregates induce selective stimulation of IgM rheumatoid factor synthesis by rheumatoid blood mononuclear cells.

Peripheral blood mononuclear cells (PBM) from patients with active rheumatoid arthritis (RA) contain precursor B lymphocytes specific for IgM rheumatoid factor (IgM-RF) synthesis. In this study, human IgG aggregates (HaIgG) were used to stimulate monocyte-depleted PBM from 46 patients with RA and 21 normal controls. The cells were incubated with HaIgG and pokeweed mitogen for 72 hours, washed, and then cultured in microwells for an additional 11 days. HaIgG induced an increase in IgM-RF synthesis by RA cells with optimum response at 0.1 microgram/ml (P less than 0.001). Total IgM synthesis remained unchanged. In contrast, HaIgG did not stimulate IgM-RF production by normal cells. Specificity of the IgM-RF response was shown by the concomitantly increased IgM-RF/IgM ratios, while IgM anti-trinitrophenyl antibodies did not increase. Aggregation of the IgG was required for it to be an effective stimulus. The findings suggest that circulating immune complexes in RA patients may provide the stimulus for sustained production of IgM-RF in vivo.