Sesquiterpenoids and Cytochalasins with Immunosuppressive Activity from Sonchus wightianus.

The plant species, Sonchus wightianus DC., was historically used in China for both medicinal and dietary uses. In present study, seven new guaiane sesquiterpenoids (1-7) and one cytochalasin (8), along with five known guaianes (9-13) and two known cytochalasins (14 and 15), were isolated from the whole plants of S. wightianus. These guaianes showed structural variations in the substituents at C-8 and/or C-15, and compounds 6 and 7 are two sesquiterpenoid glycoside derivatives. Their structures were determined by extensive analysis of spectroscopic, electronic circular dichroism, and X-ray diffraction data, and chemical method. Biological tests revealed that compounds 5 and 8 are potent and selective immunosuppressive reagents.

Source Apportionment, Hydrodynamic Influence, and Environmental Stress of Pharmaceuticals in a Microtidal Estuary with Multiple Outlets in South China.

Pharmaceutical residues in the environment are of great concern as ubiquitous emerging contaminants. This study investigated the presence of 40 pharmaceuticals in water and sediment of the Pearl River Estuary (PRE) in the wet season of 2020. Among psychiatric drugs, only diazepam was found in water samples while six of them were detected in the sediment. The Σantibiotics levels ranged from 6.18 to 35.9 ng/L and 2.63 to 140 ng/g dry weight in water and sediment samples, respectively. Fluoroquinolones and tetracyclines were found well settling in the outlet sediment, while sulfonamides could be released from disturbed sediment under stronger tidal wash-out conditions. After entering the marine waters, pharmaceuticals tended to deposit at the PRE mouth by the influence of the plume bulge and onshore invasion of deep shelf waters. Low ecological risks to the aquatic organisms and of causing antimicrobial resistance were identified. Likewise, hydrological modeling results revealed insignificant risks: erythromycin-H2O and sulfamethoxazole discharged through the outlets constituted 30.8% and 6.74% of their environmental capacity, respectively. Source apportionment revealed that pharmaceutical discharges through the Humen and Yamen outlets were predominantly of animal origin. Overall, our findings provide strategic insights on environmental regulations to further minimize the environmental stress of pharmaceuticals in the PRE.

Diterpenoids from Sauropus spatulifolius Leaves with Antimicrobial Activities.

As a plant used in both food and medicine, Sauropus spatulifolius is consumed widely as a natural herbal tea, food source, and Chinese medicine. Inspired by its extensive applications, we conducted a systematic phytochemical study of the leaves of S. spatulifolius. Thirteen new diterpenoids, sauspatulifols A-M (1-13), including four ent-cleistanthane-type diterpenoids (1-4), eight 15,16-di-nor-ent-cleistanthane-type diterpenoids (5-12), and one 17-nor-ent-pimarane-type diterpenoid (13) as well as one known diterpenoid, cleistanthol (14), were isolated. All of these diterpenoids feature a 2α,3α-dihydroxy unit within the A ring, and their structures were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Compound 14 displayed moderate inhibitory activity against Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, and Shigella flexneri with the same minimum inhibitory concentration value of 12 µg/mL as well as activity against vesicular stomatitis virus and influenza A virus.

Isolation, purification and structural characterization of two pectin-type polysaccharides from Coreopsis tinctoria Nutt. and their proliferation activities on RAW264.7 cells.

Coreopsis tinctoria Nutt. (C.tinctoria) is an annual herb of the Compositae family with many health benefits, such as clearing heat, antioxidant and anticancer activity. In this paper, two polysaccharides were isolated from C.tinctoria, named CTAP-1 and CTAP-2, respectively. Structure of CTAP-1and CTAP-2 were elucidated by high-performance gel permeation chromatography, chemical derivative analyses, GC-MS and NMR techniques. Results reveal that they both CTAP-1 and CTAP-2 consisted of predominant amounts of galacturonic acid residues along with small amounts of arabinose, rhamnose and galactose.Both them contain homogalacturonan and rhammnogalcturan I regions in different ratio, suggesting their pectin-type features. The proliferation activities of CTAP-1 and CTAP-2 on RAW264.7 cells in vitro were detected. Results show both them have the significant proliferation effect on RAW264.7 cells when the concentration from 40 to 200 µg/mL. Given their structural characteristics and proliferation activities, the pectins are expected to be potential natural immune modulators, which need further study.

Clinical value of miR-135 and miR-20a combined with multi-detector computed tomography in the diagnosis of gastric cancer.

BACKGROUND: To study the clinical value of miR-135 and miR-20a combined with multi-detector computed tomography (MDCT) in the diagnosis of gastric cancer (GC). METHOD: A total of 146 patients with GC admitted to our hospital from January 2017 to June 2019 were selected and enrolled in the GC group. Another 103 patients with gastritis received in the same period were selected for the non-GC group. Besides, 95 healthy subjects who received physical examination in our hospital were selected into the healthy control group. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of serum miR-135 and miR-20a for each group. MDCT was used for detecting the clinical staging map of the enrolled patients. Pearson's correlation analysis was used to analyze the correlation between serum miR-135 and miR-20a in patients with GC. The receiver operating characteristic (ROC) curve was drawn to analyze value of miR-135 and miR-20a in the diagnosis of GC. RESULTS: Compared with non-GC group and healthy control group, the levels of serum miR-135 and miR-20a increased significantly in the GC group, while no significant difference was found between non-GC group and healthy control group (P > 0.05). Analysis of the relationship with clinical characteristics showed that the expression of serum miR-135 and miR-20a in the GC group was significantly correlated with the progression of GC, TNM stage, degrees of differentiation, status of lymph node metastasis, and distant metastasis (P < 0.01). Pearson's correlation analysis results showed positive correlations between miR-135 and miR-20a (r = 0.634, P = 0.000). The ROC analysis results showed that the optimal diagnostic values of miR-135 and miR-20a for GC were 7.56 and 5.82 respectively. The area under the curve (AUC) was 0.873 and 0.793 respectively. The 95% confidence interval (CI) was 0.811-0.935 and 0.697-0.890 respectively. The sensitivity and specificity of miR-135 and miR-20a combined with MDCT in the diagnosis of GC were 90.41% and 93.20% respectively. The sensitivity of combined use was significantly higher than that of single detection (P < 0.01). CONCLUSION: There are high expression levels of serum miR-135 and miR-20a in patients with GC. A combined detection of miR-135 and miR-20a with MDCT can improve the diagnostic sensitivity of GC and improve the accuracy of the final diagnosis. Therefore, multiple combined detection is valuable in the diagnosis of GC.

Effects of Triple-Mutated Hypoxia-Inducible Factor-1α on Angiogenesis and Cardiac Function Improvement in Rats with Myocardial Infarction.

BACKGROUND/AIMS: The effects of hypoxia-inducible factor-1α (HIF-1α) on angiogenesis and cardiac function improvement in rats with myocardial infarction (MI) is unknown and our current study was to evaluate whether HIF-1α would be beneficial for angiogenesis and cardiac function improvement in MI rats. METHODS: A mutant of adenovirus HIF-1α (Ad-HIF-1α-Trip) was constructed by three sites mutation (Pro402, Pro564 and Asn803) in HIF-1α. The rat MI model was produced by permanent ligation of left anterior descending artery and 1×109 PFU adenovirus (Ad) vector particles of Ad-Null, Ad- HIF-1a-564/402, Ad- HIF-1a-Trip, 250ng vascular endothelial growth factor (VEGF) in 0.5ml saline or only 0.5 ml saline were injected intramuscularly around the infarct border zone. Real-time PCR, ELISA and western blotting were used to evaluate angiogenesis factors expression. Capillary density and necrotic areas were detected by immunohistochemistry staining and TTC staining, respectively. Cardiac function assessment was done by echocardiography before operation and on day 7, 14 and 28 after MI. Blood samples were drawn for the measurement of cardiac biomarkers, liver function and kidney function. RESULTS: On day 7, compared to the other groups, the expressions of HIF-1α and angiogenesis factors, and the capillary density were all significantly higher in the Ad-HIF-1α-Trip group. However, on day 28, no significant between-group differences were observed. After 72 hours of MI, serum level of cardiac biomarkers and the necrotic areas were significantly lower in the Ad-HIF-1a-Trip group compared to the other groups. Echocardiography showed that on day 7, cardiac functions were significantly reduced in all groups compared to the baseline. Cardiac function in the Ad-HIF-1α-Trip group was decreased less profoundly through day 7 to day 28 compared to the other groups. Importantly, no significant differences in liver and renal function were observed. CONCLUSION: Mutation of Pro402, Pro564 and Asn803 are beneficial for enhancement of the efficacy of HIF-1α. Ad-HIF-1α-Trip is able to improve angiogenesis and cardiac function, which may be a promising avenue for treatment of ischemic heart disease in the future.

Inhibition of protein kinase CK2 sensitizes non-small cell lung cancer cells to cisplatin via upregulation of PML.

Non-small cell lung carcinoma (NSCLC), a malignancy of lungs, is very aggressive and usually ends up with a dismal prognosis. Cisplatin (CDDP)-based systemic chemotherapy is the main pharmaceutical approach for treating NSCLC, but its effect is discounted by some hitherto unknown reasons. Thus, this study is dedicated to improving the efficacy of CDDP. Our results show that combining use of CDDP with CK2 siRNA or inhibitor is more efficient in suppressing cancer cell growth and promoting apoptosis than use of CDDP alone. The underlying mechanism is that CDDP has two pathways to go: one is that it directly induces apoptosis and the other is that it activates CK2, which suppresses proapoptosis gene promyelocytic leukemia (PML). In conclusion, inhibiting CK2 can enhance sensitivity of CDDP to NSCLC cancer cells through PML.

Ginsenoside Rd attenuates mitochondrial permeability transition and cytochrome C release in isolated spinal cord mitochondria: involvement of kinase-mediated pathways.

Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has multifunctional activity via different mechanisms and neuroprotective effects that are exerted probably via its antioxidant or free radical scavenger action. However, the effects of Rd on spinal cord mitochondrial dysfunction and underlying mechanisms are still obscure. In this study, we sought to investigate the in vitro effects of Rd on mitochondrial integrity and redox balance in isolated spinal cord mitochondria. We verified that Ca2+ dissipated the membrane potential, provoked mitochondrial swelling and decreased NAD(P)H matrix content, which were all attenuated by Rd pretreatment in a dose-dependent manner. In contrast, Rd was not able to inhibit Ca2+ induced mitochondrial hydrogen peroxide generation. The results of Western blot showed that Rd significantly increased the expression of p-Akt and p-ERK, but had no effects on phosphorylation of PKC and p38. In addition, Rd treatment significantly attenuated Ca2+ induced cytochrome c release, which was partly reversed by antagonists of Akt and ERK, but not p-38 inhibitor. The effects of bisindolylmaleimide, a PKC inhibitor, on Rd-induced inhibition of cytochrome c release seem to be at the level of its own detrimental activity on mitochondrial function. Furthermore, we also found that pretreatment with Rd in vivo (10 and 50 mg/kg) protected spinal cord mitochondria against Ca2+ induced mitochondrial membrane potential dissipation and cytochrome c release. It is concluded that Rd regulate mitochondrial permeability transition pore formation and cytochrome c release through protein kinases dependent mechanism involving activation of intramitochondrial Akt and ERK pathways.

Diagnostic Value of X-Map Images Reconstructed by Plain Dual-Energy Computed Tomography Scans in Acute Ischemic Stroke.

OBJECTIVE: This study aimed to evaluate the diagnostic value of X-Map reconstruction based on Dual-Energy Computed Tomography (DECT) in acute ischemic stroke (AIS). METHODS: Sixty-six cases of suspected AIS patients hospitalized from November, 2021 to April, 2022 were retrospectively selected. DECT, Computed Tomography Perfusion imaging (CTP), Computed Tomography Angiography (CTA), and MRI were all performed within 24 hours after symptom onset. As the gold standard for diagnosing AIS, a total of 53 patients were diagnosed with AIS based on the diffusion-weighted imaging positive results in MRI. The Chi-square test was used to evaluate the diagnostic efficacy of AIS among X-Map, CTP, and CTA. RESULTS: In the 53 patients with confirmed ASI, a total of 72 lesions were detected, including in the frontal lobes (n=33), parietal lobes (n=7), temporal lobes (n=12), basal ganglia regions (n=12), thalamus (n=3), and pons (n=5). The case detection rate of X-Map for AIS was similar to that of CTP (p=0.151) but was significantly higher than that of CTA (p<0.001). In terms of diagnostic efficacy, among the total 66 patients enrolled, X-Map achieved a higher diagnostic sensitivity (85%) than CTP and CTA. However, CTP achieved the best diagnostic specificity (84.6%) and diagnostic accuracy (77.4%) among the diagnostic tools used. CONCLUSION: X-Map provides a better or equal clinical value for the diagnosis of AIS as compared to CTA and CTP, respectively, highlighting its potential in clinical applications.

Tracheal replacement with aortic grafts: Bench to clinical practice.

Tracheal reconstruction following extensive resection for malignant or benign lesions remains a major challenge in thoracic surgery. Numerous studies have attempted to identify the optimal tracheal replacement with different biological or prosthetic materials, such as various homologous and autologous tissues, with no encouraging outcomes. Recently, a few clinical studies reported attaining favorable outcomes using in vitro or stem cell-based airway engineering and also with tracheal allograft implantation following heterotopic revascularization. However, none of the relevant studies offered a standardized technology for airway replacement. In 1997, a novel approach to airway reconstruction was proposed, which involved using aortic grafts as the biological matrix. Studies on animal models reported achieving in-vivo cartilage and epithelial regeneration using this approach. These encouraging results inspired the subsequent application of cryopreserved aortic allografts in humans for the first time. Cryopreserved aortic allografts offered further advantages, such as easy availability in tissue banks and no requirement for immunosuppressive treatments. Currently, stented aortic matrix-based airway replacement has emerged as a standard approach, and its effectiveness was also verified in the recently reported TRITON-01 study. In this context, the present review aims to summarize the current status of the application of aortic grafts in tracheal replacement, including the latest advancements in experimental and clinical practice.

[Water holding characteristics of litters of typical forest in loess area of Western Shanxi Province, China]. / æ™‹è¥¿é»„åœŸåŒºå ¸åž‹æž—åˆ†æž¯è½ç‰©æŒæ°´ç‰¹æ€§.

It is of great significance to investigate the volume and water holding characteristics of litters for the accurate evaluation of forest water conservation function. With Pinus tabuliformis, Robinia pseudoacacia, Populus davidiana, Quercus wutaishanica and Platycladus orientalis as the research objects in the Loess Plateau of Western Shanxi Province, we analyzed the thickness of undecomposed layer and semi-decomposed layer, the volume of litter, and the relationship between the litter water-holding characteristics and the immersion time for different stands by the combination of sample survey and indoor immersion test. The results showed that the total thickness of litter layer was 4.06-5.12 cm, with the thickest layer in R. pseudoacacia forest and the thinnest in P. tabuliformis forest. The storage volume of litter was the largest in Q. wutaishanica (24.39 t·hm-2), followed by P. davidiana (23.64 t·hm-2), P. orientalis (22.51 t·hm-2), and R. pseudoacacia (22.48 t·hm-2), and the smallest in P. tabuliformis (20.42 t·hm-2). The volume in the undecomposed layer was less than that in the semi-decomposed layer. The maximum water holding of litter was 40.41-79.56 t·hm-2, with the highest of Q. wutaishanica and the lowest of P. tabuliformis. The effective interception rate of litter was 108%-188%. The changes of water capacity and water absorption rate of litter were most rapid in Q. wutaishanica, P. davidiana and R. pseudoacacia, and the changes were faster in the semi-decomposed layer than in the undecomposed layer. The water-holding capacity of litter in five forests was following an order of Q. wutaishanica>P. davidiana>R. pseudoacacia>P. orientalis>P. tabuliformis.

Identifying TOPK and Hypoxia Hallmarks in Esophageal Tumors for Photodynamic/Chemo/Immunotherapy and Liver Metastasis Inhibition with Nanocarriers.

Although esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers, there are major bottlenecks in its therapeutic approaches, primarily the identification of clinically relevant targets and the lack of effective targeted therapeutics. Herein, we identified the hallmarks of ESCC, namely, high T-lymphokine-activated killer cell-originated protein kinase (TOPK) expression in human ESCC tumors and its correlation with poor patient prognosis and hypoxia in the tumor microenvironment. We developed hypoxia-sensitive nanoparticles encapsulating TOPK inhibitor OTS964 and photosensitizer chlorin e6 for the imaging-directed precision therapy of ESCC tumors. The sub-100 nm monodisperse nanoparticles efficiently delivered drugs into the human ESCC KYSE 150 cancer cells to kill the cells. The nanoparticles were selectively accumulated in the ESCC tumors after intravenous (i.v.) injection, thereby enabling the diagnosis and photoacoustic imaging-guided local laser irradiation of tumors. The combination of chemotherapy and photodynamic therapy effectively eradicated human ESCC KYSE 150 tumors and inhibited liver metastasis and recurrence by suppressing TOPK and inducing ESCC cell apoptosis. The nanoparticle-based therapies further stimulated high rates of natural killer cells in ESCC tumors, thereby exhibiting the potential of immunotherapy. This study identified important therapeutic targets of ESCC tumors and delineated an effective nanocarrier-based approach for tumor microenvironment and molecular targeted therapy.

The genetic polymorphisms of key genes in WNT pathway (LRP5 and AXIN1) was associated with osteoporosis susceptibility in Chinese Han population.

BACKGROUND: Genetic factors play a critical role in the pathogenesis of osteoporosis. The imbalance of WNT/ß-catenin will cause the occurrence of osteoporosis. LRP5 and AXIN1 play an important role in the classical Wnt/ß-catenin signaling pathway. Our study was aimed to determine the association between five candidate single nucleotide polymorphisms (SNPs) of LRP5 or AXIN1 and osteoporosis susceptibility in Chinese Han population. METHODS: A total of 599 osteoporosis patients and 599 healthy individuals were recruited for this case-control study. Agena MassARRAY was used to genotype SNPs. The association between SNPs and osteoporosis susceptibility in different genetic models was analyzed by PLINK software. We used false-positive report probability (FPRP) analysis to detect whether the positive results were just chance or noteworthy observations. Multifactor dimension reduction (MDR) was used to analyze the interaction of SNP-SNP in the osteoporosis risk. Finally, haplotype analysis was performed by plink1.07 and Haploview software. RESULTS: We found that LRP5 rs11228240, AXIN1 rs2301522, and rs9921222 were significantly associated with the osteoporosis susceptibility. The results of subgroup analysis showed that LRP5 rs11228240 (protective factor) and AXIN1 rs2301522 (risk factor) were associated with the susceptibility of osteoporosis among participants who were age >60 years, female or BMI ≤ 24; AXIN1 rs9921222 significantly increased the risk of osteoporosis among participants with BMI ≤ 24. The genotype Ars2301522Crs9921222 could increase the susceptibility of osteoporosis (p = 0.026). The rs11228219LPR5, rs11228240 LPR5, rs2301522AXIN1, and rs9921222AXIN1 four-site model was the best model for predicting the osteoporosis risk (test accuracy = 0.541; CVC = 10/10). CONCLUSIONS: The LRP5-rs11228240, AXIN1-rs2301522, and AXIN1- rs9921222 were associated with osteoporosis susceptibility in Chinese Han population.

Flood Routing Model Coupled with Dynamic Leakage Losses for Ephemeral Rivers with Large Potholes.

Ephemeral rivers commonly occur in regions with a shortage of water resources, and their channel configuration tends to change substantially owing to long drying times and artificial sand extraction. During short-term water conveyance, water storage in large potholes and leakage along the dry riverbed retards the flow, which is detrimental for the river landscape and ecological water demand. The objective of this study is to evaluate the flow process corresponding to a certain release scheme. A coupled dynamic leakage loss and flood routing model was established to predict the flood routing distance for dry rivers with potholes and strong leakage. The model mainly includes three sub-models of flow dynamics, dynamic leakage loss and water balance along multiple cross sections of the river channel. The water head was dominated by flow velocity and the overflow from potholes. The model was applied to Yongding River, a typical ephemeral river in northern China, and the model parameters were calibrated and verified using monitoring data from ecological water releases into the Yongding River in 2019 and 2020, thus, making the model more stable and reliable. Finally, the model was used to evaluate the impact of cross section optimization and pothole treatment on the flow process. This study can provide scientific guidance for ecological water conveyance and the ecological restoration of ephemeral rivers.

Significant input of organophosphate esters through particle-mediated transport into the Pearl River Estuary, China.

Most organophosphate esters (OPEs) enter the marine environment through atmospheric deposition and surface runoff, yet the role of particle-mediated transport in their inputs and loss processes remains poorly understood. To fill this knowledge gap, samples of size-segregated atmospheric particles, suspended particulate matter (SPM) in seawater, and sediments in the Pearl River Estuary (PRE) were collected and analyzed for OPEs. Total concentrations of atmospheric particulate OPEs showed a decreasing trend with increasing offshore distance in the PRE. The spatial and vertical distribution patterns of OPEs in SPM were diverse, which could be largely affected by physicochemical properties of SPM, marine microbial activities, hydrodynamic conditions, and environmental factors. Sediment in the region close to Modaomen outlet was subject to relatively high OPE concentrations. Approximately 24,100 and 65,100 g d-1 of particulate OPEs were imported into the PRE through atmospheric deposition and surface runoff, respectively; 83,200 g d-1 of which were exported to the open sea. The input and environmental fate of particulate OPEs were found to be dependent on sources, particulate media, and chemical species. The present study provides insights into the influence of OPEs in the PRE through particle-mediated transport and calls for more concern on anthropogenic impact on the estuary.

Occurrence, spatial distribution, and partitioning behavior of marine lipophilic phycotoxins in the Pearl River Estuary, South China.

The occurrence, spatial distribution, and partitioning behavior of 17 marine lipophilic phycotoxins (MLPs) in surface and bottom seawater, particulate organic matter (POM), and surface sediment from the Pearl River Estuary (PRE) were investigated to understand current contamination and the potential risks to marine ecosystems in this region. Nine MLPs were detected, including azaspiracid1-3, gymnodimine, okadaic acid, dinophysistoxin 1-2, pectenotoxin2 (PTX2), and homoyessotoxin, with Σ17MLP concentrations ranging 545-12,600 pg L-1 and 619-8,800 pg L-1 in surface and bottom seawater, respectively; 0-294 ng g-1 and 0.307-300 ng g-1 dry weight (dw) in surface and bottom POM, respectively; and 3.90-982 pg g-1 dw in surface sediment. Lower Σ17MLP levels in the seawater were found at the mouth of the PRE, and gradually increased with increasing distance offshore. According to the calculated partition coefficient, the affinity of MLPs for the aquatic environment components was as follows (from highest to lowest): POM > seawater > sediment. Overall, the distribution and migration of MLPs in the PRE may depend on partition coefficients, the organic carbon fraction, and environmental factors.

Structure of a laminarin-type ß-(1→3)-glucan from brown algae Sargassum henslowianum and its potential on regulating gut microbiota.

A homogeneous polysaccharide named SHNP with apparent molecular weight of 8.4 kDa was purified from brown algae Sargassum henslowianum using ethanol precipitation, ion-exchange chromatography, and gel-filtration column chromatography. Structural analyses reveal that SHNP is completely composed of glucose, and its backbone consists of ß-D-(1→3)-Glcp with side chains comprising t-ß-D-Glcp attached at the O-6 position. Thus, SHNP is a laminarin-type polysaccharide. In vitro fermentation test results showed that SHNP was digested by gut microbiota; the pH value in the fecal culture of SHNP was significantly decreased; and total short-chain fatty acids, acetic, propionic and n-butyric acids were significantly increased. Furthermore, SHNP regulated the intestinal microbiota composition by stimulating the growth of species belonging to Enterobacteriaceae while depleting Haemophilus parainfluenzae and Gemmiger formicilis. Taken together, these results indicate that SHNP has the potential for regulating gut microbiota, but its specific role in the regulation requires to be further investigated.

Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKIs resistance via the miR-30a-5p/ROR1 axis in non-small cell lung cancer.

Exosomes are messengers for intercellular communication and signal transduction. Circular RNA (circRNA) abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. In the present study, exosomes in the serum of five patients with non-small cell lung cancer (NSCLC) were isolated before and after EGFR-TKIs resistance, and the circRNA expression profile was screened using a circRNA microarray. The effects of the exosome circRNA_102481 on cell proliferation and apoptosis were analyzed. The interaction between miR-30a-5p and circRNA_102481 or ROR1 was predicted by starBase software, and was confirmed by RNA pull-down and dual-luciferase reporter assays. The results showed that exosomes containing circRNA_102481 were significantly up-regulated in NSCLC with EGFR-TKIs resistance (p<0.05), and that circRNA_102481 was mainly secreted by EGFR-TKIs resistance cell via exosomes (p<0.05). Both circRNA_102481 silencing and si-circRNA_102481 transported by exosomes could inhibit EGFR-TKIs resistance cell proliferation and promote cell apoptosis and circRNA_102481 overexpression could promote EGFR-TKIs sensitive cell proliferation and inhibit cell apoptosis in vitro (p<0.05). CircRNA_102481 served as a miR-30a-5p sponge to regulate ROR1 expression (p<0.05). Furthermore, the expression of circRNA_102481 in exosomes was associated with TNM stage, tumor differentiation status, brain metastasis, and PFS and OS duration. Therefore, it was concluded that tumor-derived exosomal circRNA_ 102481 could contribute to EGFR-TKIs resistance via the microRNA-30a-5p/ROR1 axis in NSCLC. Exosomal circRNA_102481 may serve as a novel diagnostic biomarker and a therapeutic target for EGFR-TKIs resistance in NSCLC.

[A comparative study of survival time of surgery combined with chemotherapy and non-surgical chemotherapy in SCLC].

OBJECTIVE: To compare the survival time of surgery combine with chemotherapy with non-surgery chemotherapy in SCLC. METHODS: 37 SCLC post operation patients were received 4-6 cycles of chemotherapy of "etoposide + cisplatin or carboplatin". 37 SCLC patients were selected be control group, whose age, stage and site of tumor were similar to surgery combine with chemotherapy group, and received 6 cycles of chemotherapy of "etoposide + cisplatin or carboplatin". Two groups were followed up 5 year and compared with the survival time. RESULTS: The 1, 3, 5 year survival rate of surgery combined with chemotherapy group were 72.97%, 35.13%, 21.62%. The 1, 3, 5 year survival rate of control group were 54.05%, 13.51%, 5.41%. The survival rate of stage I (P = 0.01) was significantly different, but stage II (P = 0.06) and stage III (P = 0.836) were no difference between the two group of SCLC. CONCLUSION: It was found that surgery combined with chemotherapy got satisfactory effects in stage I SCLC.

Structural characterization, antioxidant and immunomodulatory activities of a neutral polysaccharide from Cordyceps militaris cultivated on hull-less barley.

A water-soluble neutral polysaccharide (SDQCP-1) was isolated from fruit bodies of Cordyceps militaris cultivated on hull-less barley. SDQCP-1 was composed of mannose, glucose and galactose in the mole ratio of 13.3:1.0:9.7, with an average molecular weight of 19.3 kDa. Based on results from methylation analysis, GC-MS and NMR, SDQCP-1 was elucidated to be a glucogalactomannan with a backbone composed of (1→2)-α-D-Manp (48.4 %) and (1 → 4)-ß-D-Glcp (1.2 %) residues. Its side chains were branched at O-6 position of (1→2)-α-D-Manp mainly by (1 → 2)-ß-D-Galf or (1 → 6)-α-D-Manp residues which were terminated mainly with α-D-Galf, α-D-Galp residues. Besides exhibiting a good antioxidant capacity with an ORACFL value of 24.7 mmol Trolox/g and a TEAC value of 202.4 µmol Trolox/g, SDQCP-1 also could stimulate macrophages to release NO, TNF-α, IL-6, and IL-10, and mainly induced M1 polarization of macrophages. The findings indicated that SDQCP-1, from C. militaris cultivated on hull-less barley, could be used as potential natural antioxidant and immunomodulator in functional foods or medicine.