Disparities in mortality risk after diagnosis of hematological malignancies in 185 countries: A global data analysis.

This study was to report proxy measures for mortality risk in patients with hematological malignancies across 185 countries globally and explore its association with their socioeconomic status and treatment. The incidence, mortality, and 5-year prevalence data were extracted from the GLOBOCAN database. The data regarding the human development index (HDI), gross national income (GNI), vulnerability index, and concordance with cancer Essential Medicines List (EML) were obtained from open-source reports. The ratio of mortality to 5-year-prevalence (MPR) and that of mortality to incidence (MIR) were calculated and age-standardized using Segi's world standard population. Finally, the possible associations were assessed using Pearson correlation analyses. In 2020, the global incidence, mortality, and 5-year prevalence of HMs were 1,278,362, 711,840, and 3,616,685, respectively. Global age-standardized MPR and MIR were 0.15 and 0.44, respectively; they varied significantly among 6 regions, 185 countries, 4 HM types, and 4 HDI groups worldwide. Older populations always had higher ratios. The correlation of MPRs and MIRs with HDI, GNI, and concordance with cancer EML was negative, whereas it was positive with the vulnerability index (lower was better). Increasing access to cancer drugs in resource-limited regions with a focus on vulnerable children may aid in reducing HM-related mortality risk.

Camrelizumab plus famitinib in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-1 blockade: data from a multicohort phase 2 study.

Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens. Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381. Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6-55.4) and the DCR was 77.8% (90% CI, 56.1-92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0-not reach), and the median PFS was 7.2 months (90% CI, 4.4-13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3-4 major epistaxis, and they were cured by nasal packing and vascular embolization. Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings. Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Outcome and risk prediction of early progression in patients with extranodal natural killer/T cell lymphoma from the CLCG study.

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.

Evidence of cure for extranodal nasal-type natural killer/T-cell lymphoma with current treatment: an analysis of the CLCG database.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.

The relationship between shifts in the rhizosphere microbial community and root rot disease in a continuous cropping American ginseng system.

The root rot disease causes a great economic loss, and the disease severity usually increases as ginseng ages. However, it is still unclear whether the disease severity is related to changes in microorganisms during the entire growing stage of American ginseng. The present study examined the microbial community in the rhizosphere and the chemical properties of the soil in 1-4-year-old ginseng plants grown in different seasons at two different sites. Additionally, the study investigated ginseng plants' root rot disease index (DI). The results showed that the DI of ginseng increased 2.2 times in one sampling site and 4.7 times in another during the 4 years. With respect to the microbial community, the bacterial diversity increased with the seasons in the first, third, and fourth years but remained steady in the second year. The seasonal changing of relative abundances of bacteria and fungi showed the same trend in the first, third, and fourth years but not in the second year. Linear models revealed that the relative abundances of Blastococcus, Symbiobacterium, Goffeauzyma, Entoloma, Staphylotrichum, Gymnomyces, Hirsutella, Penicillium and Suillus spp. were negatively correlated with DI, while the relative abundance of Pandoraea, Rhizomicrobium, Hebeloma, Elaphomyces, Pseudeurotium, Fusarium, Geomyces, Polyscytalum, Remersonia, Rhizopus, Acremonium, Paraphaeosphaeria, Mortierella, and Metarhizium spp. were positively correlated with DI (P < 0.05). The Mantel test showed that soil chemical properties, including available nitrogen, phosphorus, potassium, calcium, magnesium, organic matter, and pH, were significantly correlated to microbial composition. The contents of available potassium and nitrogen were positively correlated with DI, while pH and organic matter were negatively correlated with DI. In summary, we can deduce that the second year is the key period for the shift of the American ginseng rhizosphere microbial community. Disease aggravation after the third year is related to the deterioration of the rhizosphere microecosystem.

Characteristics and prognosis of distant metastasis after primary treatment for early-stage extranodal nasal-type natural killer/T-cell lymphoma from the China Lymphoma Collaborative Group database.

This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early-stage extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM-free survival (DMFS) and overall survival (OS). The 5-year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis - distant LN, SST, extracutaneous site, and lymphoma-associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late-onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early-stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

Influence of age on long-term net survival benefit for early-stage MALT lymphomas treated with radiotherapy: A SEER database analysis (2000-2015).

BACKGROUND: Given the lower incidence of lymphoma-related death but higher background mortality in patients with early-stage mucosa-associated lymphoid tissue (MALT) lymphoma, it is critically important to examine how age affects a treatment's survival benefit. METHODS: 9,467 patients with early-stage MALT lymphoma in the Surveillance, Epidemiology, and End Results (SEER) database treated between 2000-2015 were extracted and analyzed. Primary therapy was classified as radiotherapy (n = 3,407), chemotherapy (n = 1,294), and other/unknown treatments including observation (n = 4,766). Inverse probability of treatment weighting (IPTW) was conducted to balance baseline characteristics between groups. Relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression were conducted to compare survival differences between treatment modalities by controlling for the background mortality. Radiotherapy-age interaction was examined. RESULTS: Across age-groups, early-stage MALT lymphoma patients were at lower risk of lymphoma-related death than death due to other causes. The 10-year overall survival (OS, 73.8 %) and RS (96.6 %) rates were significantly higher, and the SMR (1.14) significantly lower, with radiotherapy than with chemotherapy (OS, 61.7 %; RS, 86.4 %; SMR, 1.54; P < 0.001) or other/unknown treatments (OS, 61.1 %; RS, 87.2 %; SMR, 1.41; P < 0.001). By multivariable analysis and IPTW, radiotherapy remained an independent predictor of better RS (HR 0.81, 95 %CI, 0.73-0.89; P < 0.001). A significant interaction between age and radiotherapy was identified for both RS (Pinteraction = 0.016) and OS (Pinteraction = 0.024), indicating greater benefit in young adults. CONCLUSION: Radiotherapy was associated with significantly better survival in early-stage MALT lymphoma, especially in young adults.

Application of vermicompost and biochar suppresses Fusarium root rot of replanted American ginseng.

Soil sterilization integrated with agronomic measures is an effective method to reduce soilborne replant diseases. However, the effect of vermicompost or biochar application after soil sterilization on soilborne diseases is poorly understood. A pot experiment was conducted in American ginseng to investigate the effects of vermicompost (VF), biochar (BF), and a combination of vermicompost and biochar (VBF) applied after soil sterilization on the incidence of Fusarium root rot using natural recovery (F) as control. After one growing season, the disease index of root rot, the phenolic acids, and the microbial communities of American ginseng rhizosphere soil were analyzed. The disease index of VF, BF, and VBF decreased by 33.32%, 19.03%, and 80.96%, respectively, compared with F. The highest bacterial richness and diversity were observed in the rhizosphere soil of VBF. Besides, VF and VBF significantly increased the relative abundance of beneficial bacteria (Pseudomonas, Lysobacter, and Chryseolinea) in the rhizosphere soil. Higher concentrations of vanillin, one of the phenolic acids in the roots exudates, were recorded in the rhizosphere soils of BF and VBF. The vanillin concentration showed a significant negative correlation with the disease index. To conclude, vermicompost improved the beneficial bacteria of the rhizosphere soil, while biochar regulated the allelopathic effect of the phenolic acids. The study proposes a combined application of biochar and vermicompost to the rhizosphere soil to control Fusarium root rot of replanted American ginseng effectively. KEY POINTS: Vermicompost improves the relative abundance of rhizosphere beneficial bacteria. Biochar inhibits the degradation of phenolic acids by adsorption. The combination of vermicompost and biochar enhances the disease control effect.

[Effects of nutrients deficiency on growth and saponin accumulation of American ginseng].

Mineral nutrient elements are the key factors to maintain the growth and quality of American ginseng. In order to understand the comprehensive effect of different nutrient elements deficiency on American ginseng, 2-year-old American ginsengs were cultivated by Hoagland solution(CK) or 10 different nutrients deficiency solution in sand culture. During the cultivation, the deficient symptom was observed. The plant height, leaf area, biomass, photosynthetic index, root activity, ginsenoside content were measured. The results showed that N, K or Fe deficiency could lead to leaves of American ginseng yellowing. Deficiency N, K, Ca, Mg and B were the main factors that decrease plant height and leaf area. The biomass of plant decreased significantly in all the nutrient deficient treatments(P<0.05)compared with control group, and N, K, Ca or Fe deficiency groups descended over 50%. In the absence of N, K and Fe elements, the P_n, G_s, C_i, T_r and chlorophyll of leaves were decreased mostly. The first three factors decreasing root activity were N, K and Ca deficiency. The effects of nutrient deficiency on saponins of American ginseng were different.Generally, N, P, B, Zn and Cu deficiency resulted the synthesis of saponins decreased significantly(P<0.05). This study contributed to clarify the demand characteristics of American ginseng for different nutrient elements,which is of great significance for the diagnose of nutrient deficiency, the rational fertilizer and the improvement of yield and quality of American ginseng.

[Investigation of aflatoxins,mycobiota,and toxigenic fungi during post-harvest handling of Ziziphi Spinosae Semen].

Ziziphi Spinosae Semen is one of the Chinese herbal medicine being susceptible to aflatoxins contamination. To investigate the sources of aflatoxins contamination and toxigenic fungi species on Ziziphi Spinosae Semen,32 samples were collected from multiple steps during the post-harvest processing in this study. Aflatoxins in these samples were determined by immunoaffinity column and HPLC coupled with post-column photochemical derivatization. The dilution-plate method was applied to the fungi isolation. The isolated fungi strains were identified by morphological characterization and molecular approaches. The results showed that aflatoxins were detected in 28 samples from every step during the processing of Ziziphi Spinosae Semen. Three samples were detected with aflatoxin B_1 and 2 samples with both aflatoxin B_1 and total aflatoxin exceeding the limit of Chinese Pharmacopoeia. Especially the samples from the washing step,with the highest detected amounts of AFB_1 and AFs were reached 94. 79,121. 43 µg·kg~(-1),respectively. All 32 samples were contaminated by fungi. The fungal counts on the newly harvested samples were 2. 20 × 10~2 CFU·g~(-1). Moreover,it increased as tphreocessing progresses,and achieved 1. 16×10~6 CFU·g~(-1) after washing. A total of 321 isolates were identified to 17 genera. Aspergillus flavus was the main source of aflatoxins during the processing and storage of Ziziphi Spinosae Semen. One isolate of A. flavus was confirmed producing AFB_1 and AFB_2. The fungal count was significantly increased by composting,and Aspergillus was the predominant genus after shell breaking. The contamination level of aflatoxins was increased by composting and washing.

Dissolved methane in groundwater of domestic wells and its potential emissions in arid and semi-arid regions of Inner Mongolia, China.

Methane (CH4) is widely present in groundwater. Dissolved CH4 in groundwater is less understood when compared with that in wetlands. In this study, the concentrations and origin of dissolved CH4 in groundwater were investigated and the potential importance of groundwater CH4 emissions in arid and semi-arid regions of Inner Mongolia was discussed. Groundwater was extracted from domestic wells using a submersible pump or manual power and was analyzed for CH4 concentrations, δ13C-CH4, and physico-chemical variables. The results show that the concentrations of dissolved CH4 in groundwater had large spatial variability, ranging from 0 to 0.10 mg L-1 with a mean of 0.01 mg L-1 in Xilingol and from 0 to 8.99 mg L-1 with a mean of 1.44 mg L-1 in Xingan-Tongliao. Substantial CH4 concentrations of about 2.5-5.5 mg L-1 were found in central areas of Xingan-Tongliao in the winter and the summer. The δ13C-CH4 of about -85‰ was highly depleted while CH4 concentration was significantly negatively correlated with SO42- concentration, indicating that dissolved CH4 in groundwater was microbial in origin. This study suggests that groundwater as a source of CH4 might have great implications in arid and semi-arid regions worldwide and should deserve more research.

Intestinal Microbial Community Differs between Acute Pancreatitis Patients and Healthy Volunteers.

A case control study including 45 acute pancreatitis and 44 healthy volunteers was performed to investigate the association between intestinal microbial community and acute pancreatitis. High-throughput 16S rRNA gene amplicon sequencing was used to profile the microbiological composition of the samples. In total, 27 microbial phyla were detected and the samples of pancreatitis patients contained fewer phyla. Samples from acute pancreatitis patients contained more Bacteroidetes and Proteobacteria and fewer Firmicutes and Actinobacteria than those from healthy volunteers. PCoA analyses distinguished the fecal microbial communities of acute pancreatitis patients from those of healthy volunteers. The intestinal microbes of acute pancreatitis patients are different from those of healthy volunteers. Modulation of the intestinal microbiome may serve as an alternative strategy for treating acute pancreatitis.

Prevalence and clinical-demographic correlates of hyperhomocysteinemia in inpatients with bipolar disorder in a Han Chinese population.

Recent studies have reported that hyperhomocystinemia (HHcy) is highly prevalent in patients with bipolar disorder (BD), placing them at greater risk of cardiovascular disease and possibly serving as a disease biomarker. However, the correlation of HHcy with demographic or clinical parameters is not well known. In this study, we examined the prevalence of HHcy and its association with these parameters in a sample of Chinese BD patients. Fasting plasma homocysteine (Hcy) levels were determined in 198 BD inpatients and 84 healthy controls. HHcy was defined when Hcy concentration exceeded 15.0µmol/L. Affective symptomatology was assessed by the Young Mania Rating Scale, Hamilton Depression Rating Scale and the Clinical Global Impressions severity scale. Compared to healthy controls, BD patients had a significantly higher prevalence (34.85% vs. 19.05%) of HHcy and a higher absolute level of homocysteine. Logistic regression analysis demonstrated that BD patients with HHcy were more likely to be male, have elevated BMI, more frequent treatment on lithium but less on valproate. These results suggest that Chinese inpatients with bipolar disorder have a higher rate of HHcy than the general population, and those at greatest risk are male, have an elevated BMI, and take more lithium but less valproate therapy.

Various Antioxidant Effects Were Attributed to Different Components in the Dried Blossoms of Citrus aurantium L. var. amara Engl.

Citrus aurantium L. var. amara Engl. (CAVA) was traditionally used as an edible and medicinal material in China. Total flavonoids (CAVAF), alkaloids (CAVAA), polysaccharides (CAVAP), coumarins (CAVAC), and neroli (CAVAO) were extracted from CAVA. Hesperidin, naringin, and neohesperidin composed 83.94% of CAVAF, and synephrine represented 50.56% of CAVAA. On the basis of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS• +), hydroxyl radical (•OH), ferric-reducing antioxidant power (FRAP), and reducing power assays, the antioxidant activities of five components were comprehensively and comparatively investigated. CAVAF had a stronger DPPH• scavenging effect and FRAP and reducing power. CAVAP and CAVAA exhibited comparable •OH scavenging effects to vitamin C. CAVAA showed the highest ABTS• + scavenging activity. In conclusion, different constituents varied significantly toward different sources of free radicals and other oxidants. It is obvious that CAVA has various antioxidant effects, which are attributed to different components.

Association of 4-hydroxynonenal with classical adipokines and insulin resistance in a Chinese non-diabetic obese population.

BACKGROUND: The prevalence of obesity is increasing worldwide. Oxidative stress plays an etiological role in a variety of obesity-related metabolic disorders. 4-hydroxynonenal (4-HNE) is the most abundant and reactive aldehydic product derived from the peroxidation of n-6 polyunsaturated fatty acids with diverse biological effects that are not well detailed. Obesity is associated with decreased plasma adiponectin concentrations and increased production of lipid peroxidation products, including 4-HNE, in adipose tissue. There may be some association between the level of adipokines and 4-HNE. MATERIAL AND METHODS: To analyze the associations between 4-HNE and classical adipokines, namely, adiponectin and leptin in a Chinese population, the plasma 4-HNE, adiponectin and leptin levels of 160 non-diabetic obese (NDO) patients and 160 healthy subjects were determined by ELISA, and their associations with adiposity, glucose, lipid profiles, insulin secretion and insulin sensitivity were studied. RESULTS: Plasma 4-HNE levels were significantly increased in patients with NDO compared with healthy controls (p < 0.01). 4-HNE was negatively correlated with adiponectin and positively correlated with leptin. The plasma levels of 4-HNE were significantly correlated to several parameters involved in body mass index (BMI) and insulin resistance (IR). The 4-HNE levels were positively correlated with BMI and negatively correlated with insulin sensitivity. CONCLUSION: We conclude that 4-HNE is associated with the secretion of adiponectin and leptin and is correlated with IR in NDO humans. These findings indicate a pro-inflammatory role of 4-HNE in NDO patients, which supports the potential role of 4-HNE in the development of obesity-related disorders.

Association of 4-hydroxynonenal with classical adipokines and insulin resistance in a Chinese non-diabetic obese population / Asociación del hydroxynonenal 4 con las adipoquinas clásicas y la resistencia a la insulina en una población china obesa no diabética

Background: The prevalence of obesity is increasing worldwide. Oxidative stress plays an etiological role in a variety of obesity-related metabolic disorders. 4-hydroxynonenal (4-HNE) is the most abundant and reactive aldehydic product derived from the peroxidation of n-6 polyunsaturated fatty acids with diverse biological effects that are not well detailed. Obesity is associated with decreased plasma adiponectin concentrations and increased production of lipid peroxidation products, including 4-HNE, in adipose tissue. There may be some association between the level of adipokines and 4-HNE. Material and methods: To analyze the associations between 4-HNE and classical adipokines, namely, adiponectin and leptin in a Chinese population, the plasma 4-HNE, adiponectin and leptin levels of 160 non-diabetic obese (NDO) patients and 160 healthy subjects were determined by ELISA, and their associations with adiposity, glucose, lipid profiles, insulin secretion and insulin sensitivity were studied. Results: Plasma 4-HNE levels were significantly increased in patients with NDO compared with healthy controls (p < 0.01). 4-HNE was negatively correlated with adiponectin and positively correlated with leptin. The plasma levels of 4-HNE were significantly correlated to several parameters involved in body mass index (BMI) and insulin resistance (IR). The 4-HNE levels were positively correlated with BMI and negatively correlated with insulin sensitivity. Conclusion: We conclude that 4-HNE is associated with the secretion of adiponectin and leptin and is correlated with IR in NDO humans. These findings indicate a pro-inflammatory role of 4-HNE in NDO patients, which supports the potential role of 4-HNE in the development of obesity-related disorders (AU)

Introducción: la prevalencia de la obesidad está aumentando en todo el mundo. El estrés oxidativo desempeña un papel etiológico en una variedad de desórdenes metabólicos relacionados con la obesidad. El hydroxynonenal 4 (4-HNE) es el aldehido más abundante y más reactivo derivado de la peroxidación de los ácidos grasos poliinsaturados n-6, con efectos biológicos diversos que no son bien conocidos. La obesidad se asocia a concentraciones disminuidas de adiponectinas en el plasma y a un aumento en los productos de la peroxidación lipídica, incluyendo el 4-HNE, en tejido adiposo. Puede haber una cierta asociación entre el nivel de adipoquinas y el 4-HNE. Material y métodos: para analizar las asociaciones entre 4-HNE y las adipoquinas clásicas, adiponectina y leptina se determinaron por ELISA los niveles de adiponectina y de leptina, así como de 4-HNE, en una población de 160 pacientes chinos obesos no diabéticos (NDO) y de 160 controles sanos, y se estudió su asociación con adiposidad, perfil glucémico y lipídico, secreción de la insulina y sensibilidad de la insulina. Resultados: los niveles de 4-HNE aumentaron significativamente en los pacientes con NDO comparado con los controles sanos (p < 0,01). El nivel de 4-HNE se correlacionó negativamente con la adiponectina y positivamente con la leptina. Los niveles de 4-HNE se correlacionan positivamente con el IMC y negativamente con la sensibilidad a la insulina. Conclusión: concluimos que el 4-HNE está asociado a la secreción de adiponectina y de leptina y correlacionado con la resistencia a la insulina en sujetos obesos no diabéticos. Estos resultados indican un papel proinfl amatorio del 4-HNE en pacientes NDO, que apoya el papel potencial del 4-HNE en el desarrollo de alteraciones relacionadas con la obesidad (AU)

4-Hydroxynonenal Regulates TNF-α Gene Transcription Indirectly via ETS1 and microRNA-29b in Human Adipocytes Induced From Adipose Tissue-Derived Stromal Cells.

Obesity is characterized by an accumulation of excessive body fat and can be diagnosed by a variety of measures, such as BMI. However, in some obese individuals, oxidative stress is also thought to be an important pathogenic mechanism of obesity-associated metabolic syndrome. Oxidative stress increases the lipid peroxidation product, 4-hydroxynonenal (4-HNE), which is one of the most abundant and active lipid peroxides. Within the adipose tissue, adipocytes are derived from adipose tissue-derived stromal cells (ADSCs), which play a key role in the generation and metabolism of adipose tissue. Additionally, obesity is associated with low-grade inflammation. Specific microRNAs (miRNAs) that regulate obesity-associated inflammation are largely dysregulated in metabolic syndrome (MS). In this study, we aim to confirm whether 4-HNE and miRNAs play a role in the regulation of TNF-α gene transcription. We enrolled six obese individuals who were referred to Harbin Medical University (Heilongjiang, China) and six nonobese control participants. Plasma 4-HNE levels of the 12 subjects were determined by ELISA. Using qRT-PCR, we measured ETS1, miR-29b, SP1, and TNF-α levels in subcutaneous white adipose tissue (WAT). Furthermore, we examined the relationship between ETS1 and TNF-α using a luciferase reporter assay and a ChIP assay. Our results suggest that ETS1 promotes TNF-α gene transcription in adipocytes. In addition, we demonstrated that 4-HNE promotes TNF-α gene transcription through the inhibition of the miR-29b â†’ SP1 â†’ TNF-α pathway and promotion of the ETS1 â†’ TNF-α pathway. Anat Rec, 299:1145-1152, 2016. © 2016 Wiley Periodicals, Inc.

Clinical and prognostic differences between ALK-negative anaplastic large cell lymphoma and peripheral T cell lymphoma, not otherwise specified: a single institution experience.

Clinical differences between anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK(-) ALCL) and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), remain unclear. The aim of this study was to compare the clinical and prognostic features of these two lymphoma types. We retrospectively analyzed 167 patients with ALK(-) ALCL (n = 48) and PTCL-NOS (n = 119). Compared with ALK(-) ALCL patients, PTCL-NOS patients exhibited distinct differences in clinical features with a propensity for more advanced stages, frequent extranodal involvement, and a poor performance status, leading to a higher risk group according to the International Prognostic Index or Prognostic Index for PTCL-NOS. Patients with ALK(-) ALCL were associated with a higher complete response rate (47.9 vs. 31.0 %; P = 0.041) after initial chemotherapy than patients with PTCL-NOS. The prognosis was significantly different between two subtypes, with a 5-year overall survival (OS) rate of 57.9 % for ALK(-) ALCL and 23.9 % for PTCL-NOS (P = 0.002). The subgroup analysis showed significant differences in OS and progression-free survival between the two subtypes in early-stage diseases, but not in advanced-stage diseases. We conclude that patients with ALK(-) ALCL showed favorable clinical features, higher chemosensitivity, and a superior outcome than those with PTCL-NOS.

MicroRNA-29b promotes the adipogenic differentiation of human adipose tissue-derived stromal cells.

OBJECTIVE: Obesity is primarily characterized by the accumulation of large amounts of fat in adipose tissue. Within the adipose tissue, adipocytes are derived from adipose tissue-derived stromal cells (ADSCs) via a specialized cell lineage differentiation process, and ADSCs play a key role in the generation and metabolism of adipose tissue. This study investigated whether microRNAs (miRNAs) play a role in adipocyte differentiation. METHODS: Using luciferase reporter and ChIP assays, the relationship between miR-29b, SP1, and TNF-α was examined. RESULTS: During the normal adipogenic differentiation of ADSCs, up-regulation of miR-29b promoted adipogenesis by enhancing SP1-mediated inhibition of TNF-α. CONCLUSIONS: This study investigated the regulatory role of miR-29b during the adipogenic differentiation of ADSCs and found that miR-29b is an effective positive regulator of adipogenesis.

Soy Protein Supplementation Reduces Clinical Indices in Type 2 Diabetes and Metabolic Syndrome.

PURPOSE: Clinical trials have studied the use of soy protein for treating type 2 diabetes (T2D) and metabolic syndrome (MS). The purpose of this study was to outline evidence on the effects of soy protein supplementation on clinical indices in T2D and MS subjects by performing a meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: We searched PubMed, EMBASE, and Cochrane databases up to March 2015 for RCTs. Pooled estimates and 95% confidence intervals (CIs) were calculated by the fixed-and-random-effects model. A total of eleven studies with eleven clinical variables met the inclusion criteria. RESULTS: The meta-analysis showed that fasting plasma glucose (FPG) [weighted mean difference (WMD), -0.207; 95% CI, -0.374 to -0.040; p=0.015], fasting serum insulin (FSI) (WMD, -0.292; 95% CI, -0.496 to -0.088; p=0.005), homeostasis model of assessment for insulin resistance index (HOMA-IR) (WMD, -0.346; 95% CI, -0.570 to -0.123; p=0.002), diastolic blood pressure (DBP) (WMD, -0.230; 95% CI, -0.441 to -0.019; p=0.033), low-density lipoprotein cholesterol (LDL-C) (WMD, -0.304; 95% CI, -0.461 to -0.148; p=0.000), total cholesterol (TC) (WMD, -0.386; 95% CI, -0.548 to -0.225; p=0.000), and C-reactive protein (CRP) (WMD, -0.510; 95% CI, -0.722 to -0.299; p=0.000) are significant reduced with soy protein supplementation, compared with a placebo control group, in T2D and MS patients. Furthermore, soy protein supplementation for longer duration (≥6 mo) significantly reduced FPG, LDL-C, and CRP, while that for a shorter duration (<6 mo) significantly reduced FSI and HOMA-IR. CONCLUSION: Soy protein supplementation could be beneficial for FPG, FSI, HOMA-IR, DBP, LDL-C, TC, and CRP control in plasma.