Machine Learning in Diagnosis and Prognosis of Lung Cancer by PET-CT.

As a disease with high morbidity and high mortality, lung cancer has seriously harmed people's health. Therefore, early diagnosis and treatment are more important. PET/CT is usually used to obtain the early diagnosis, staging, and curative effect evaluation of tumors, especially lung cancer, due to the heterogeneity of tumors and the differences in artificial image interpretation and other reasons, it also fails to entirely reflect the real situation of tumors. Artificial intelligence (AI) has been applied to all aspects of life. Machine learning (ML) is one of the important ways to realize AI. With the help of the ML method used by PET/CT imaging technology, there are many studies in the diagnosis and treatment of lung cancer. This article summarizes the application progress of ML based on PET/CT in lung cancer, in order to better serve the clinical. In this study, we searched PubMed using machine learning, lung cancer, and PET/CT as keywords to find relevant articles in the past 5 years or more. We found that PET/CT-based ML approaches have achieved significant results in the detection, delineation, classification of pathology, molecular subtyping, staging, and response assessment with survival and prognosis of lung cancer, which can provide clinicians a powerful tool to support and assist in critical daily clinical decisions. However, ML has some shortcomings such as slightly poor repeatability and reliability.

NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction.

AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.

Machine learning and new insights for breast cancer diagnosis.

Breast cancer (BC) is the most prominent form of cancer among females all over the world. The current methods of BC detection include X-ray mammography, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and breast thermographic techniques. More recently, machine learning (ML) tools have been increasingly employed in diagnostic medicine for its high efficiency in detection and intervention. The subsequent imaging features and mathematical analyses can then be used to generate ML models, which stratify, differentiate and detect benign and malignant breast lesions. Given its marked advantages, radiomics is a frequently used tool in recent research and clinics. Artificial neural networks and deep learning (DL) are novel forms of ML that evaluate data using computer simulation of the human brain. DL directly processes unstructured information, such as images, sounds and language, and performs precise clinical image stratification, medical record analyses and tumour diagnosis. Herein, this review thoroughly summarizes prior investigations on the application of medical images for the detection and intervention of BC using radiomics, namely DL and ML. The aim was to provide guidance to scientists regarding the use of artificial intelligence and ML in research and the clinic.

Machine Learning Predicts the Oxidative Stress Subtypes Provide an Innovative Insight into Colorectal Cancer.

So far, it has been reached the academic consensus that the molecular subtypes are via genomic heterogeneity and immune infiltration patterns. Considering that oxidative stress (OS) is involved in tumorigenesis and prognosis prediction, we propose an innovative classification of colorectal cancer- (CRC-) OS subtypes. We obtain three datasets from The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) online databases. 1399 OS-related genes were selected from the GeneCards database. We remove the batch effect before conducting differentially expressed genes (DEGs) analyses between normal and tumor samples. Nonnegative matrix factorization (NMF) was used to perform an unsupervised cluster. Lasso regression and Cox regression were used to construct the signature model. DEGs, robust rank aggregation, and protein-protein interaction networks were used to select hub genes, and then use hub genes to predict OS subtypes by random forest algorithms. NMF identifies two OS-related subtypes of CRC patients. Eight OS-related gene signatures were built to predict the outcome of patients, based on the DEGs between two subtypes. A total of 61 DEGs overlap each dataset, and the RRA analysis shows that 17 genes are important in these three datasets, and 15 genes are shared genes between the two methods. PPI network suggests that five hub genes are confirmed, they are SPP1, SERPINE1, CAV1, PDGFRB, and PLAU. These five hub genes could predict the OS-related subtype of CRC accurately with AUC equal to 0.771. In our study, we identify two OS-related subtypes, which will provide an innovative insight into colorectal cancer.

Identification and validation of novel prognostic fatty acid metabolic gene signatures in colon adenocarcinoma through systematic approaches.

Background: Colorectal cancer (CRC) belongs to the class of significantly malignant tumors found in humans. Recently, dysregulated fatty acid metabolism (FAM) has been a topic of attention due to its modulation in cancer, specifically CRC. However, the regulatory FAM pathways in CRC require comprehensive elucidation. Methods: The clinical and gene expression data of 175 fatty acid metabolic genes (FAMGs) linked with colon adenocarcinoma (COAD) and normal cornerstone genes were gathered through The Cancer Genome Atlas (TCGA)-COAD corroborating with the Molecular Signature Database v7.2 (MSigDB). Initially, crucial prognostic genes were selected by uni- and multi-variate Cox proportional regression analyses; then, depending upon these identified signature genes and clinical variables, a nomogram was generated. Lastly, to assess tumor immune characteristics, concomitant evaluation of tumor immune evasion/risk scoring were elucidated. Results: A 8-gene signature, including ACBD4, ACOX1, CD36, CPT2, ELOVL3, ELOVL6, ENO3, and SUCLG2, was generated, and depending upon this, CRC patients were categorized within high-risk (H-R) and low-risk (L-R) cohorts. Furthermore, risk and age-based nomograms indicated moderate discrimination and good calibration. The data confirmed that the 8-gene model efficiently predicted CRC patients' prognosis. Moreover, according to the conjoint analysis of tumor immune evasion and the risk scorings, the H-R cohort had an immunosuppressive tumor microenvironment, which caused a substandard prognosis. Conclusion: This investigation established a FAMGs-based prognostic model with substantially high predictive value, providing the possibility for improved individualized treatment for CRC individuals.

The roles of lncRNA functions and regulatory mechanisms in the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent and deadly type of liver cancer. While the underlying molecular mechanisms are poorly understood, it is documented that lncRNAs may play key roles. Many HCC-associated lncRNAs have been linked to HBV and HCV infection, mediating gene expression, cell growth, development, and death. Studying the regulatory mechanisms and biological functions of HCC-related lncRNAs will assist our understanding of HCC pathogenesis as well as its diagnosis and management. Here, we address the potential of dysregulated lncRNAs in HCC as diagnostic and therapeutic biomarkers, and we evaluate the oncogenic or tumor-suppressive properties of these lncRNAs.

Systematic evaluation of irinotecan-induced intestinal mucositis based on metabolomics analysis.

Chemotherapy-induced intestinal mucositis (CIM) is a major dose-limiting side effect of chemotherapy, especially in regimens containing irinotecan (CPT-11). Several studies on the pathologic mechanisms of CIM focused on both the genomics and molecular pathways triggered by chemotherapy. However, systematic evaluation of metabolomic analysis in irinotecan-induced intestinal mucositis (IIM) has not been investigated. This study aimed to comprehensively analyze metabolite changes in main tissues of IIM mouse models. Male ICR mice were assigned to two groups: the model group (n = 11) treated with CPT-11 (20 mg/kg daily; i.p.) and the control group (n= 11) with solvent for 9 days. Gas chromatography-mass spectrometry (GC-MS) was used to investigate the metabolic alterations in the serum, intestinal, colonic, hepatic, and splenic samples of mice between two groups by multivariate statistical analyses, including GC-MS data processing, pattern recognition analysis, and pathway analysis. Forty-six metabolites, including hydrocarbons, amino acids, lipids, benzenoids, hydroxy acids, and amines, had significant changes in levels in tissues and sera of IIM mouse models. The most important pathways related to the identified metabolites were the glycerolipid metabolism in the colon and aminoacyl-tRNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism in the liver. Our study firstly provided a comprehensive and systematic view of metabolic alterations of IIM using GC-MS analysis. The characterizations of metabolic changes could offer profound and theoretical insight into exploring new biomarkers for diagnosis and treatment of IIM.

Comprehensive evaluation of caloric restriction-induced changes in the metabolome profile of mice.

OBJECTS: Caloric restriction (CR) is known to extend lifespan and exert a protective effect on organs, and is thus a low-cost and easily implemented approach to the health maintenance. However, there have been no studies that have systematically evaluated the metabolic changes that occur in the main tissues affected by CR. This study aimed to explore the target tissues metabolomic profile in CR mice. METHODS: Male C57BL/6J mice were randomly allocated to the CR group (n = 7) and control group (n = 7). A non-targeted gas chromatography-mass spectrometry approach and multivariate analysis were used to identify metabolites in the main tissues (serum, heart, liver, kidney, cortex, hippocampus, lung, muscle, and white adipose) in model of CR. RESULTS: We identified 10 metabolites in the heart that showed differential abundance between the 2 groups, along with 9 in kidney, 6 in liver, 6 in lung, 6 in white adipose, 4 in hippocampus, 4 in serum, 3 in cortex, and 2 in muscle. The most significantly altered metabolites were amino acids (AAs) (glycine, aspartic acid, L-isoleucine, L-proline, L-aspartic acid, L-serine, L-hydroxyproline, L-alanine, L-valine, L-threonine, L-glutamic acid, and L-phenylalanine) and fatty acids (FAs) (palmitic acid, 1-monopalmitin, glycerol monostearate, docosahexaenoic acid, 16-octadecenoic acid, oleic acid, stearic acid, and hexanoic acid). These metabolites were associated with 7 different functional pathways related to the metabolism of AAs, lipids, and energy. CONCLUSION: Our results provide insight into the specific metabolic changes that are induced by CR and can serve as a reference for physiologic studies on how CR improves health and extends lifespan.

The Intestinal Redox System and Its Significance in Chemotherapy-Induced Intestinal Mucositis.

Chemotherapy-induced intestinal mucositis (CIM) is a significant dose-limiting adverse reaction brought on by the cancer treatment. Multiple studies reported that reactive oxygen species (ROS) is rapidly produced during the initial stages of chemotherapy, when the drugs elicit direct damage to intestinal mucosal cells, which, in turn, results in necrosis, mitochondrial dysfunction, and ROS production. However, the mechanism behind the intestinal redox system-based induction of intestinal mucosal injury and necrosis of CIM is still undetermined. In this article, we summarized relevant information regarding the intestinal redox system, including the composition and regulation of redox enzymes, ROS generation, and its regulation in the intestine. We innovatively proposed the intestinal redox "Tai Chi" theory and revealed its significance in the pathogenesis of CIM. We also conducted an extensive review of the English language-based literatures involving oxidative stress (OS) and its involvement in the pathological mechanisms of CIM. From the date of inception till July 31, 2021, 51 related articles were selected. Based on our analysis of these articles, only five chemotherapeutic drugs, namely, MTX, 5-FU, cisplatin, CPT-11, and oxaliplatin were shown to trigger the ROS-based pathological mechanisms of CIM. We also discussed the redox system-mediated modulation of CIM pathogenesis via elaboration of the relationship between chemotherapeutic drugs and the redox system. It is our belief that this overview of the intestinal redox system and its role in CIM pathogenesis will greatly enhance research direction and improve CIM management in the future.

NLRP3 inflammasome links vascular senescence to diabetic vascular lesions.

Vascular senescence is inextricably linked to the onset and progression of cardiovascular diseases (CVDs), which are the main cause of mortality in people with Type 2 diabetes (T2DM). Previous studies have emphasized the importance of chronic aseptic inflammation in diabetic vasculopathy. Here, we found the abnormal activation of NLRP3 inflammasome in the aorta of both old and T2DM mice by immunofluorescence and Western Blot analysis. Histopathological and isometry tension analysis showed that the presence of T2DM triggered or aggravated the increase of vascular aging markers, as well as age-associated vascular impairment and vasomotor dysfunction, which were improved by NLRP3 deletion or inhibition. Differential expression of aortic genes links to senescence activation and vascular remodeling supports the favorable benefits of NLRP3-/- during T2DM. In vitro results based on primary mice aortic endothelial cells (MAECs) and vascular smooth muscle cells (VSMCs) demonstrate that NLRP3 deficiency attenuated premature senescence and restored proliferation and migration capability under-stimulation, and partially ameliorated replicative senescence. These results provide an insight into the critical role of NLRP3 signaling in T2DM-induced vascular aging and loss of vascular homeostasis, and provide the possibility that targeting NLRP3 inflammasome might be a promising strategy to prevent diabetic vascular senescence and associated vascular lesions.

Paris saponin VII, a Hippo pathway activator, induces autophagy and exhibits therapeutic potential against human breast cancer cells.

Dysregulation of the Hippo signaling pathway seen in many types of cancer is usually associated with a poor prognosis. Paris saponin VII (PSVII) is a steroid saponin isolated from traditional Chinese herbs with therapeutic action against various human cancers. In this study we investigated the effects of PSVII on human breast cancer (BC) cells and its anticancer mechanisms. We showed that PSVII concentration-dependently inhibited the proliferation of MDA-MB-231, MDA-MB-436 and MCF-7 BC cell lines with IC50 values of 3.16, 3.45, and 2.86 µM, respectively, and suppressed their colony formation. PSVII (1.2-1.8 µM) induced caspase-dependent apoptosis in the BC cell lines. PSVII treatment also induced autophagy and promoted autophagic flux in the BC cell lines. PSVII treatment decreased the expression and nuclear translocation of Yes-associated protein (YAP), a downstream transcriptional effector in the Hippo signaling pathway; overexpression of YAP markedly attenuated PSVII-induced autophagy. PSVII-induced, YAP-mediated autophagy was associated with increased active form of LATS1, an upstream effector of YAP. The activation of LATS1 was involved the participation of multiple proteins (including MST2, MOB1, and LATS1 itself) in an MST2-dependent sequential activation cascade. We further revealed that PSVII promoted the binding of LATS1 with MST2 and MOB1, and activated LATS1 in the BC cell lines. Molecular docking showed that PSVII directly bound to the MST2-MOB1-LATS1 ternary complex. Microscale thermophoresis analysis and drug affinity responsive targeting stability assay confirmed the high affinity between PSVII and the MST2-MOB1-LATS1 ternary complex. In mice bearing MDA-MB-231 cell xenograft, administration of PSVII (1.5 mg/kg, ip, 4 times/week, for 4 weeks) significantly suppressed the tumor growth with increased pLATS1, LC3-II and Beclin 1 levels and decreased YAP, p62 and Ki67 levels in the tumor tissue. Overall, this study demonstrates that PSVII is a novel and direct Hippo activator that has great potential in the treatment of BC.

Paris saponin VII, a direct activator of AMPK, induces autophagy and exhibits therapeutic potential in non-small-cell lung cancer.

Paris saponin VII (PSVII), a bioactive constituent extracted from Trillium tschonoskii Maxim., is cytotoxic to several cancer types. This study was designed to explore whether PSVII prevents non-small-cell lung cancer (NSCLC) proliferation and to investigate its molecular target. AMP-activated protein kinase (AMPK) has been implicated in the activation of autophagy in distinct tissues. In cultured human NSCLC cell lines, PSVII induces autophagy by activating AMPK and inhibiting mTOR signaling. Furthermore, PSVII-induced autophagy activation was reversed by the AMPK inhibitor compound C. Computational docking analysis showed that PSVII directly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation. Microscale thermophoresis assay and drug affinity responsive target stability assay further confirmed the high affinity between PSVII and AMPK. In summary, PSVII acts as a direct AMPK activator to induce cell autophagy, which inhibits the growth of NSCLC cells. In the future, PSVII therapy should be applied to treat patients with NSCLC.

Albumin-bilirubin score is associated with response to pegylated interferon and nucleos(t)ide analogues in chronic hepatitis B patients.

BACKGROUND AND AIM: Recently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. METHODS: The ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. RESULTS: ALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. CONCLUSIONS: ALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.

Inhibition of vascular adventitial remodeling by netrin-1 in diabetic rats.

Cardiovascular complications of type 2 diabetes mellitus (T2DM) are associated with vascular remodeling in the arteries. Perivascular sympathetic neurons release an abundance of trophic factors to regulate vascular function via a paracrine signaling. Netrin-1, a diffusible protein that can be secreted outside the cell, is one of common signals of 'conversation' between nerve and vessel. The present study investigated whether netrin-1 is a novel modulator of sympathetic neurons paracrine signaling and played a critical role in vascular adventitial remodeling under T2DM. Vascular adventitial remodeling was observed in adventitial fibroblasts (AFs) responding to netrin-1 deficiency in the supernatant from primary rat superior cervical ganglia (SCG) neurons, shown as AFs proliferation, migration, and collagen deposition. Conditioned medium from the high glucose (HG)-treated SCG neurons contributed to AFs remodeling, which was effectively alleviated by exogenous netrin-1 supplementation. Further, it was found that uncoordinated-5-B (Unc5b) was mainly expressed in AFs among netrin-1 specific receptors. Treatment of netrin-1 inhibited H2O2 production derived from NADPH oxidase 4 (NOX4) through the UNC5b/CAMP/PKA signal pathway in AFs remodeling. In vivo, aorta adventitial remodeling was accompanied with the downregulation of netrin-1 in the perivascular sympathetic nerve in T2DM rats. Such abnormalities were restored by netrin-1 intervention, which was associated with the inhibition of NOX4 expression in the aorta adventitia. In conclusion, netrin-1 is a novel modulator of sympathetic neurons paracrine signaling to maintain AFs function. Vascular adventitial remodeling was aggravated by sympathetic neurons paracrine signaling under hyperglycemia, which was ameliorated by netrin-1 treatment through the UNC5b/CAMP/PKA/NOX4 pathway.

Urotensin II and urantide exert opposite effects on the cellular components of atherosclerotic plaque in hypercholesterolemic rabbits.

Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg-1· h-1) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque.

Significant Increase of Aromatics-Derived Secondary Organic Aerosol during Fall to Winter in China.

Human activities release large amounts of anthropogenic pollutants into the air, and thereby produce substantial secondary organic aerosol (SOA). Aromatic hydrocarbons (AHs) that mainly emitted from coal combustion, transportation, solvent use and biofuel/biomass burning, are a major class of anthropogenic SOA precursors. At present, there are few field studies focusing on AH-derived SOA (SOAA) on a continental scale, especially in polluted regions of the world. In this study, a one-year concurrent observation of the SOAA tracer, 2,3-dihydroxy-4-oxopentanoic acid (C5H8O5, DHOPA) was carried out at 12 sites across six regions of China for the first time. The annual averages of DHOPA among the 12 sites ranged from 1.23 to 8.83 ng m-3 with a mean of 3.48 ± 1.96 ng m-3. At all observation sites, the concentrations of DHOPA from fall to spring were significantly higher than those in summertime, and positive correlations were observed between DHOPA and the biomass burning tracer (levoglucosan). This indicated that such a nationwide increase of SOAA during the cold period was highly associated with the enhancement of biomass burning emission. In the northern China, the highest levels of DHOPA were observed in the coldest months during winter, probably due to the enhancement of biofuel and coal consumption for household heating. In the southern China, the highest levels of DHOPA were mostly observed in fall and spring, which were associated with the enhancement of open biomass burning. The apparent increases of DHOPA and levoglucosan levels during the cold period and the negative correlations of visibility with DHOPA and levoglucosan imply that the reduction of SOAA amount and biomass burning emission is an efficient way to reduce haze pollution during fall to winter in China.

Spatial and seasonal variations of isoprene secondary organic aerosol in China: Significant impact of biomass burning during winter.

Isoprene is a substantial contributor to global secondary organic aerosol (SOA). The formation of isoprene SOA (SOAI) is highly influenced by anthropogenic emissions. Currently, there is rare information regarding SOAI in polluted regions. In this study, one-year concurrent observation of SOAI tracers was undertaken at 12 sites across China for the first time. The tracers formed from the HO2-channel exhibited higher concentrations at rural sites, while the tracer formed from the NO/NO2-channel showed higher levels at urban sites. 3-Methyltetrahydrofuran-3,4-diols exhibited linear correlations with their ring-opening products, C5-alkenetriols. And the slopes were steeper in the southern China than the northern China, indicating stronger ring-opening reactions there. The correlation analysis of SOAI tracers with the factor determining biogenic emission and the tracer of biomass burning (levoglucosan) implied that the high level of SOAI during summer was controlled by biogenic emission, while the unexpected increase of SOAI during winter was largely due to the elevated biomass burning emission. The estimated secondary organic carbon from isoprene (SOCI) exhibited the highest levels in Southwest China. The significant correlations of SOCI between paired sites implied the regional impact of SOAI in China. Our findings implicate that isoprene origins and SOAI formation are distinctive in polluted regions.

Assessment of the use of immunosuppressants combined with cord blood for severe aplastic anemia.

BACKGROUND: The objective of this study was two-fold: 1) to investigate the changes of cytokines concentration in relation to severe aplastic anemia (SAA) when treated with immunosuppressants combined with cord blood (IS + CBI). and 2) to assess the curative effect of umbilical cord blood chimerism engraftment. METHODS: We selected 43 patients with SAA all treated with IS + CBI (newly diagnosed group). Among them, a total of 33 patients were treated effectively (effective group) while 10 cases were treated invalidly (invalid group). An additional 20 healthy individuals were selected as control (control group). The expression levels of IL-17, IL-22 and other cytokines in each group were detected by ELISA. The engraftment of cord blood stem cells was detected by using short tandem repeat-polymerase chain reaction (STR-PCR). RESULTS: 1. IL-17, IL-22 and other cytokines expressions in the newly diagnosed group were significantly higher than in the control group. 2. After six months, the levels in the effective group were significantly lower than pre-therapy levels (P < 0.05). The levels in the invalid group did not differ to those observed prior treatment. 3. After one and three months of treatment, a small amount of engraftment was found in the effective group. However, after six months, transplant rejection was observed in all patients. No effective engraftment was observed in the invalid group. CONCLUSION: 1) Th17 and Th22 producing cells in SAA patients significantly increased indicating a positive correlation between these biomarkers and the progression of SAA. 2) During the IS + CBI treatment the maintenance of a normal hematopoietic function depended on immunesup-pressants. Early umbilical cord blood chimerism engraftment may promote hematopoietic recovery.

Mechanism of immunosuppressants combined with cord blood for severe aplastic anemia.

This study aims to explore the mechanism of immunosuppressants combined with cord blood (IS + CBI) for severe aplastic anemia. Selecting 30 patients with SAA and all treated with IS + CBI (newly diagnosed group). 23 patients who were treated effectively (effective group) while 7 cases were treated invalidly (invalid group). Another 20 healthy individuals were selected as control group. To detect the expression levels of IL-17, IL-22 and other cytokines by ELISA method in each group. To detect the engraftment of cord blood stem cells by using short tandem repeat-polymerase chain reaction (STR-PCR) method. 1. IL-17, IL-22 and other cytokines expressions in newly diagnosed group were significantly higher than in the control group. 2. After 6 months, the level in effective group was significantly lower than pretherapy (P < 0.05).The level in invalid group had no obvious difference than pretherapy. 3. After 1 month and 3 months of treatment, a small amount of engraftment was found in effective group. After 6 months, implant rejection was showed. No effective engraftment was observed in invalid group. 1. IL-17, IL-22 cells in SAA patients increased which might positively correlated with the progression of SAA. 2. During the treatment of IS + CBI, there is a bridging mechanism between the early stage of engraftment and the advanced stage of immunosuppressant adjustment. The first 3 months after treatment, it relies on the engraftment of cord blood stem cells to promote hematopoietic recovery and 3 months later, it relies on immunosuppressants to maintain normal hematopoietic function.