Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer.

BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

Is there role of adjuvant radiotherapy after complete resection of locally advanced nonsmall cell lung cancer?

PURPOSE OF REVIEW: This review aims to provide a timely and relevant overview of the role of postoperative radiotherapy (PORT) in completely resected stage IIIA-N2 nonsmall cell lung cancer (NSCLC). Given the controversy surrounding the use of PORT and the emergence of advanced radiation techniques and therapies, this review provides valuable insight into current and potential treatment strategies. RECENT FINDINGS: The Lung ART and PORT-C trials have provided valuable insights into the efficacy of PORT in stage IIIA-N2 NSCLC. While the results have been mixed, studies have shown that advanced radiation techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy, can reduce cardiopulmonary toxicities associated with PORT. Molecular targeted therapies and immunotherapies have also shown potential in improving NSCLC treatment outcomes. SUMMARY: The role of radiotherapy becomes smaller and smaller in new era. However, it is too early to abolish radiotherapy for all the patients after complete resection of locally advanced NSCLC. Nowadays, it is recommended to adopt individualized treatment approaches guided by multidisciplinary team consultations. The integration of IMRT, proton therapy, and emerging therapies offers the potential to enhance treatment efficacy while minimizing toxicity. Further research is needed to optimize the use of PORT and explore the method to identify the patients who can really benefit from PORT.

Measurement of the 134Xe(n,2n)133m,gXe and 136Xe(n,2n)135m,gXe reaction cross-sections and isomeric ratios induced by the 14.8 MeV neutrons.

The precise measurement of the (n, 2n) reaction cross-sections of xenon isotopes is of great significance for the diagnosis of the Inertial Confinement Fusion fuel area density ρR. The preparation of xenon samples and how they can be efficiently adsorbed to obtain an optimal reaction cross section are extremely difficult in existing experiments. This work aims to use the 93Nb(n,2n)92mNb reaction cross section as the standard to calculate the cross-sections and isomeric ratio for 134Xe(n,2n)133m,gXe and 136Xe(n,2n)135m,gXe reactions. This work also aims to explore the feasibility of adsorbent selection, the method of adsorption sample and the feasibility of the method used in the laboratory. In this paper, the Geant4 program was used to simulate and calculate the adsorption factors of activated carbon and polymer for standard 152Eu multi-line sources, so as to determine the most suitable adsorption material. Next, the GammaVision analysis software was used to observe whether the characteristic γ-rays released by other isotope reaction products of xenon in the sample and packaging material had an effect on the characteristic γ-rays of the target product. Then, the basic principle of activation method and the relative measurement principle are used to calculate the cross-sections and isomeric ratio for 134Xe(n,2n)133Xe and 136Xe(n,2n)135Xe reactions. Finally, the experimental results are compared and analyzed with the existing data in EXFOR database to verify whether the experimental method is correct.

Effects of dexmedetomidine administration on outcomes in critically ill patients with acute kidney injury: A propensity score-matching analysis.

PURPOSE: To evaluate the effects of dexmedetomidine (DEX) on outcomes of critically ill patients with acute kidney injury (AKI). MATERIALS AND METHODS: Data were extracted from the Medical Information Mart for Intensive Care III database (MIMIC III). Propensity score matching (PSM) analysis (1 : 3), Cox proportional hazards model, linear regression and logistic regression model were used to assess the effect of DEX on clinical outcomes. RESULTS: After PSM, 324 pairs of patients were matched between the patients with DEX administration and those without. DEX administration was associated with decreased in-hospital mortality (hazard ratio (HR) 0.287; 95% CI 0.151 - 0.542; p < 0.001) and 90-day mortality (HR 0.344; 95% CI 0.221 - 0.534; p < 0.001), and it was also associated with reduced length of stay (LOS) in ICU (4.54 (3.13,7.72) vs. 5.24 (3.15,10.91), p < 0.001) and LOS in hospital (11.63 (8.02,16.79) vs 12.09 (7.83,20.44), p = 0.002). Subgroup analysis showed that the above associations existed only in the mild and moderate AKI subgroups, but not in the severe AKI subgroup. Nevertheless, DEX administration was not associated with recovery of renal function (HR 1.199; 95% CI 0.851 - 1.688; p = 0.300). CONCLUSION: DEX administration improved outcomes in critically ill patients with mild and moderate AKI and could be a good choice of sedation.

Combining geophysics, remote sensing and numerical simulation to assess GLOFs: Case study of the Namulacuo Lake in the Southeastern Tibetan Plateau.

The current highest glacial lake outburst floods (GLOFs) risk level is centered in the eastern Himalaya. GLOFs represent a serious threat to downstream inhabitants and ecological environment. In the context of climate warming on the Tibetan Plateau, such GLOFs will continue or even intensify in the future. Remote sensing and statistical methods are often used to diagnose glacial lakes with the highest outburst probability. These methods are efficient in large-scale glacial lake risk assessment but do not take into consideration the complexity of specific glacial lake dynamics and triggering factor uncertainty. Therefore, we explored a novel approach to integrate geophysics, remote sensing, and numerical simulation in glacial lake and GLOF disaster chain assessments. In particular, geophysical techniques are rarely applied to the exploration of glacial lakes. The Namulacuo Lake located in the southeastern Tibetan Plateau is considered as the experimental site. The current status of the lake, including landform construction and identifying potential triggering factors, was first investigated. Secondly, the outburst process and disaster chain effect were evaluated by numerical simulation based on the multi-phase modeling frame proposed by Pudasaini and Mergili (2019) implemented in the open source computational tool r.avaflow. The results allowed verifying that the Namulacuo Lake dam was a landslide dam with an obvious layered structure. Also, the piping-induced flood might have more severe consequences than the short-term ultra-high discharge flood caused by surge. The blocking event caused by a surge disappeared faster than that caused by piping. Therefore, this comprehensive diagnostic approach can assist GLOF researchers to increase their understanding of key challenges they are facing regarding GLOF mechanisms.

TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism.

Blockade of the T cell immunoreceptor with the immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) can enhance innate and adaptive tumor immunity and radiotherapy (RT) can enhance anti-tumor immunity. However, our data suggest that TIGIT-mediated immune suppression may be an impediment to such goals. Herein, we report on the synergistic effects of RT combined with anti-TIGIT therapy and the mechanism of their interaction. Treatment efficacy was assessed by measuring primary and secondary tumor growth, survival, and immune memory capacity. The function of CD103 + dendritic cells (DCs) under the combined treatment was assessed in wild-type and BATF3-deficient (BATF3-/-) mice. FMS-like tyrosine kinase 3 ligand (Flt3L) was used to confirm the role of CD103 + DCs in RT combined with anti-TIGIT therapy. TIGIT was upregulated in immune cells following RT in both esophageal squamous cell carcinoma patients and mouse models. Administration of the anti-TIGIT antibody enhanced the efficacy of RT through a CD8 + T cell-dependent mechanism. It was observed that RT and the anti-TIGIT antibody synergistically enhanced the accumulation of tumor-infiltrating DCs, which activated CD8 + T cells. The efficacy of the combination therapy was negated in the BATF3-/- mouse model. CD103 + DCs were required to promote the anti-tumor effects of combination therapy. Additionally, Flt3L therapy enhanced tumor response to RT combined with TIGIT blockade. Our study demonstrated TIGIT blockade can synergistically enhance anti-tumor T cell responses to RT via CD8 + T cells (dependent on CD103 + DCs), suggesting the clinical potential of targeting the TIGIT pathway and expanding CD103 + DCs in RT.

Disubstituted pyrimidine-5-carboxamide derivatives as novel HIV-1 NNRTIs: Crystallographic overlay-based molecular design, synthesis, and biological evaluation.

Herein, via crystallographic overlay-based molecular hybridization strategy, a series of disubstituted pyrimidine-5-carboxamide derivatives were designed by introducing an amide moiety to the central core of the lead etravirine. All the newly synthesized compounds were evaluated for their anti-HIV-1 potencies in MT-4 cells using the MTT method. Most of the synthesized compounds displayed promising antiviral activities against the wild-type (IIIB) and a panel of HIV-1 NNRTIs-resistant strains. Especially, 21c exhibited the most potent activity (EC50 = 0.009-0.065 µM) against HIV-1 IIIB, L100I, K103N, Y181C, Y188L, and RES056, being comparable to those of etravirine. The inhibitory activity to reverse transcriptase (RT) was evaluated by ELISA method, and the target of the compounds was proved to be RT. Moreover, the molecular docking was investigated to clarify the binding mode of 21c with RT. Overall, the results demonstrated that 21c could serve as a lead for further modification to develop novel HIV-1 NNRTIs.

Identification of Boronate-Containing Diarylpyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors.

In this study, privileged boronic acid ester was introduced into the right wing of etravirine (ETR) to obtain a series of novel boronate-containing derivatives. These newly synthesized derivatives were evaluated for their anti-HIV potency in MT-4 cells using the MTT method, and their inhibitory activity to HIV-1 reverse transcriptase (RT) was assayed by the ELISA method. Most of the synthesized compounds displayed promising antiviral activity against the wild-type and a wide range of HIV-1 mutant strains. In particular, 4a exhibited the most potent activity against the wild-type and a panel of single mutations (L100I, K103N, Y181C, and E138K) with EC50 values ranging from 0.005 to 0.648 µM, which were much superior to those of nevirapine (EC50 = 0.151 µM). Moreover, 4b turned out to be an effective inhibitor against the double-mutant strains F227L + V106A and RES056 with EC50 values of 3.21 and 2.30 µM, respectively. RT inhibition activity and molecular docking were also investigated.

Efficacy and safety of immune checkpoint inhibitors plus anlotinib in small cell lung cancer with brain metastases: a retrospective, multicentre study.

BACKGROUND: Previous studies showed that both immune checkpoint inhibitors (ICIs) and anlotinib have central nervous system (CNS) efficacy. This study aimed to evaluate the efficacy and safety of ICIs combined with anlotinib in small cell lung cancer (SCLC) patients with brain metastases (BMs). METHODS: We retrospectively reviewed SCLC patients with CNS metastases confirmed by brain magnetic resonance imaging (MRI). Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and Response assessment in neuro-oncology brain metastases (RANO-BM) were used to evaluate treatment response to ICIs plus anlotinib. Kaplan-Meier analysis and Cox regression analysis were performed to determine patient's prognosis. RESULTS: Sixty-six patients with baseline BMs were included. For patients with measurable intracranial lesions, the intracranial objective response rate (ORR) was 29.2% based on RECIST 1.1 criteria and was 27.1% based on RANO-BM criteria. The median intracranial progression-free survival (PFS) was 9.0 months (95% confidence interval [CI], 6.5-11.5 months). The median overall survival (OS) was 13.4 months (95% CI, 10.7-20.5 months). Multivariate Cox regression analysis showed that high disease burden (hazard ratio [HR] = 4.83, P < 0.001), multiple BMs (HR = 2.71, P = 0.036), and more than or equal to 3 prior lines of therapy (HR = 2.56, P = 0.023) were independent negative predictors of OS. The overall incidence of treatment-related adverse events (TRAEs) was 75.8%, and grade 3-4 TRAEs were reported in 19.7% of patients. CONCLUSIONS: Our results suggested that ICIs plus anlotinib had potent CNS efficacy with tolerable toxicity and could be a promising treatment option for SCLC patients with BMs.

Measurement of the 59Co(n,2n)58Co reaction cross section induced by 14.8 MeV neutrons.

The measurement of the 59Co(n,2n)58Co reaction cross section with the neutron energy of 14.8 MeV has been performed by the activation method and relative measurement principle. The 300 kV Cockcroft Walton Accelerator of China Institute of Atomic Energy was used to produce quasi monoenergetic neutron beams by the T(D, n)4He reaction. Two thin 27Al and 93Nb foils were attached to the 59Co target and performed as monitors. After the irradiation, the HPGe detector and the GammaVision software were used to measure the activity of the irradiated samples and record the counts of γ-rays, respectively. Finally, some relevant physical quantities were corrected after comparing the results with experimental data in the EXFOR database and evaluated data in the ENDF database.

TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/ß­catenin and Akt/mTOR signaling pathways.

TGFB induced factor homeobox 1 (TGIF1), a transcriptional corepressor, has been reported to be involved in tumorigenesis and cancer development. However, the role of TGIF1 in the growth and metastasis of esophageal cancer is poorly studied. In the present study, it was found that TGIF1 was highly expressed in esophageal cancer tissues and cell lines. The silencing of TGIF1 by siRNA interference significantly inhibited the proliferation, migration, invasion and epithelial­mesenchymal transition (EMT) process of KYSE­150 esophageal cancer cells, and promoted cell apoptosis. Correspondingly, the upregulation of TGIF1 significantly promoted the proliferation and metastatic potential of Eca­109 cells, and reduced apoptosis. Furthermore, the data indicated that the Wnt/ß­catenin and Akt/mammalian target of rapamycin (mTOR) signaling pathways were inhibited by TGIF1 knockdown, and were promoted by the overexpression of TGIF1. It was also confirmed that TGIF1 knockdown reduced tumor growth, inhibited Wnt/ß­catenin and Akt/mTOR pathway activation, and reversed the TGF­ß1­mediated EMT process in a tumor xenograft model. Taken together, the data of the present study suggest that TGIF1 plays an oncogenic role in the progression of esophageal cancer. It may carry out this role by regulating the Wnt/ß­catenin and Akt/mTOR signaling pathways.

Effects of Different Exercise Interventions on Cardiac Function in Rats With Myocardial Infarction.

BACKGROUND: High-intensity interval training (HIIT) and aerobic training (AT) both improve cardiac function; however, their effects on cardiac function after myocardial infarction (MI) and the molecular mechanisms are unclear. In this study, HIIT, AT and sedentary (SED) interventions were performed for 4 weeks to compare the effects on cardiac function after MI and explore a more suitable approach for clinical application and the potential mechanisms. METHODS: Twenty-four (24) male rats were randomly divided into a control group (CON), MI-sedentary group (MI-SED), MI-aerobic training group (MI-AT), and MI-high-intensity interval training group (MI-HIIT). After 4 weeks of intervention the exercise capacity, heart rate (HR), left ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), AMP-activated protein kinase α1 (AMPKα1), cardiomyocyte morphology, and cardiac mitochondria were assessed. RESULTS: After intervention: 1) exercise capacity in the MI-AT (49.08±3.141 m; p<0.001) and MI-HIIT (51.70±7.572 m; p<0.001) groups was significantly more increased than the MI-SED group; there was no significant difference between the MI-AT and MI-HIIT group (p=0.33). 2) LVEDD and LVESD in the MI-SED (p<0.01) and MI-HIIT (p<0.01) groups was significantly more increased than the CON group; the MI-AT group showed no significant difference in LVEDD and LVESD compared with the CON group; LVEF in the MI-AT (53.47±7.913%; p=0.03) and MI-HIIT (56.20±7.224%; p=0.006) groups was significantly more increased than the MI-SED group, and there was no statistical difference between the MI-AT and MI-HIIT groups. 3) AMPKα1 expression was significantly increased in the MI-AT (1.15±0.264; p=0.001) and MI-HIIT (1.04±0.238; p=0.003) groups and decreased in the MI-SED group (0.71±0.257; p<0.001) when compared with the CON group. 4) The MI-SED group exhibited sarcoplasmic dissolution and fibrous hyperplasia in the myocardium, cardiac mitochondrial damage and reduced mitochondrial numbers; the MI-HIIT group displayed swollen and vacuolated cardiac mitochondria with disrupted cristae; the MI-AT and MI-HIIT groups had significantly increased cardiac mitochondrial numbers than the MI-SED group; there was no statistical difference between the MI-AT and MI-HIIT groups. CONCLUSIONS: Aerobic training and HIIT for 4 weeks had similar cardioprotection and were superior to SED intervention. Both AT and HIIT improved cardiac function and exercise capacity by upregulating AMPKα1 expression. However, 4 weeks of intervention resulted in left ventricular dilation and cardiac myocardial mitochondrial injury in the MI-HIIT group.

Perspective on treatment for unresectable locally advanced non-small cell lung cancer with oncogene-driven mutation: a narrative review.

The standard treatment of unresectable locally advanced non-small cell lung cancer (LA NSCLC) is concurrent chemoradiotherapy. With the addition of immunotherapy, patients with LA NSCLC received a significantly prolonged outcome, while patients with harboring epidermal growth factor receptor (EGFR) mutation benefited less. Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of stage IV with harboring EGFR mutation and anaplastic lymphoma kinase rearrangement, but there are few recommendations indicating whether TKI treatment is effective in unresectable NSCLC. Preclinical studies have shown that TKIs could have a radiosensitizing effect, which provided a rationale to consider the application TKI with radiotherapy. In this review, we summarize the clinical studies that have used TKIs in LA-NSCLC as well as ongoing trials, and discuss recent progress in research related to the efficacy of TKI for unresectable LA NSCLC patients. Recent results of small studies evaluating TKI therapy for LA NSCLC patients in combination with radiation or chemoradiation demonstrated promising efficacy, improved outcomes with a tolerable toxicity profile. However, there is a lack of strong evidence for TKI treatment in unresectable LA NSCLC, because of unpowered statistics, lack of molecular selection, or lack of large randomized arms. We prospect the combination of TKI and radiation or chemoradiation therapy might eventually replace the current standard treatment for patients with LA NSCLC harboring oncogene-driven mutation.

Long non-coding RNAs as targets for immunosuppressive drug teriflunomide in anti-cancer potential for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Because of the relatively chemotherapy-refractory nature of HCC and significant potential poor hepatic reserve, chemotherapy has not been used consistently in the treatment of HCC. Effective new drugs for HCC are urgently needed. Teriflunomide, which was approved for the treatment of relapsing forms of multiple sclerosis (MS), has been identified as a potential antineoplastic drug. Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer than 200 nucleotides that lack protein coding potential. In this study, we investigated the ability of teriflunomide to act as an antineoplastic drug by examining the effects of teriflunomide treatment on HCC cells. Teriflunomide strongly inhibited the proliferation of HCC cells, induced cell apoptosis and induced cell accumulation in S phases of the cell cycle. LncRNA and mRNA expression profiles of HCC cells treated with teriflunomide compared with controls were performed by using microarray analysis. For comparison, the differentially expressed mRNAs were annotated by using gene ontology (GO) and pathway analyses. The microarray revealed that 2085 lncRNAs and 1561 mRNAs differed in the cells treated with teriflunomide compared with controls. Several GO terms including protein folding, mitochondrial outer membrane, transmembrane receptor protein phosphatase activity, negative regulation of cellular biosynthetic process, DNA packaging complex, and receptor signaling protein activity were enriched in gene lists, suggesting a potential correlation with the action mechanism of teriflunomide. Pathway analysis then demonstrated that JAK-STAT signaling pathway may play important roles in the cell apoptosis induced by teriflunomide. Co-expression network analysis indicated that a number of lncRNAs and mRNAs were included in the co-expression network, and p34710_v4 is the lncRNA with highest degree. Then the mRNAs associated with those differentially expressed lncRNAs were also annotated by using gene ontology (GO) and pathway analyses. The pathway analyses shows that teriflunomide significantly inhibited cell proliferation and promoted cell apoptosis partly by participating in Wnt signaling pathways. These findings suggest that teriflunomide could be a potential drug for chemotherapy and molecularly targeted therapies of HCC.

Nimotuzumab, an EGFR­targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma.

Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor (EGFR)­targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR­targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE­1, with or without nimotuzumab, were first evaluated by CCK­8 assay. Colony formation and apoptosis were used to measure anti­proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2 phase in vitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P<0.001 for 0 Gy pre­irradiation, P=0.005 for 20 Gy pre­irradiation, P=0.005 for 10 Gy pre­irradiation). These results suggest that nimotuzumab combined with radiation may be an effective means to control recurrent esophageal squamous cell carcinoma with EGFR overexpression.

Mineral Fabric as a Hidden Variable in Fracture Formation in Layered Media.

Two longstanding goals in subsurface science are to induce fractures with a desired geometry and to adaptively control the interstitial geometry of existing fractures in response to changing subsurface conditions. Here, we demonstrate that microscopic mineral fabric and structure interact with macroscopic strain fields to generate emergent meso-scale geometries of induced fractures. These geometries define preferential directions of flow. Using additively manufactured rock, we demonstrate that highly conductive flow paths can be formed in tensile fractures by creating corrugated surfaces. Generation, suppression and enhancement of corrugations depend on the relative orientation between mineral fabric and layering. These insights into the role of micro-scale structure on macro-scale flow provide a new method for designing subsurface strategies to maximize potential production or to inhibit flow.

R-spondin family members as novel biomarkers and prognostic factors in lung cancer.

The R-spondin (RSPO) family of secreted proteins consists of four members that have critical roles in embryonic development and organogenesis. However, the expression patterns and the exact roles of the individual RSPO family members in tumorigenesis and progression of lung cancer are unknown, particularly in non-small cell lung cancer, which accounts for 85% of all lung cancer cases. In the present study, data from the ONCOMINE database was used to compare the RNA expression levels of RSPOs in multiple different types of cancer with normal controls. The expression profiles of RSPOs in various types of cancer cell lines were subsequently compared based on data from the Broad Institute Cancer Cell Line Encyclopedia. Using the Kaplan-Meier plotter, the prognostic value of expression of the different RSPOs members was determined for different pathological subtypes of lung cancer. When compared with normal tissues, expression of RSPO1, RSPO2 and RSPO3 was significantly lower in patients with lung cancer. In the survival analysis, increased mRNA expression levels of RSPO1, RSPO2 and RSPO3 were associated with increased survival in patients with lung adenocarcinomas. These results suggest that RSPO1, RSPO2 and RSPO3 may serve as distinct biomarkers and prognostic factors in patients with lung cancer.

Ten-Year Outcomes Of Intensity-Modulated Radiotherapy (IMRT) Combine With Chemotherapy Versus IMRT Alone For Stage II Nasopharyngeal Carcinoma In The Real-World Study (RWD).

OBJECTIVES: The aim was to define the role of chemotherapy in stage II nasopharyngeal carcinoma (NPC) and to identify the toxicity of chemotherapy for these patients in the era of intensity-modulated radiotherapy (IMRT). METHODS: Between January 2002 and December 2013, 169 patients with stage II NPC were analyzed. Of these patients, 149 patients treated with chemotherapy were divided into three groups as follows: neoadjuvant chemotherapy followed by IMRT (NCT) group, concurrent chemotherapy with IMRT (CCRT) group, and neoadjuvant chemotherapy followed by CCRT (NC+CCRT) group. In addition, 20 patients received IMRT alone. We retrospectively assessed the 10-year survival and acute adverse effects in the patients using SPSS software. RESULTS: The median follow-up time was 93 months (2-160 months). The 10-year OS of the NCT, CCRT, NC+CCRT groups vs the IMRT alone group was 69.8%, 63.4%, 69.7% vs 72.4%, respectively (P=0.664, 0.940, and 0.998, respectively). Both univariable and multivariable analyses showed that the addition of chemotherapy to IMRT did not significantly improve the 10-year survival outcomes. The hematotoxicity and mucous reaction of patients with chemotherapy were more serious than those with IMRT alone (P=0.007 and 0.049). Distant metastasis for stage II NPC patients mostly occurred within 3 years, which is very different from patients with advanced NPC. CONCLUSION: Patients with stage II NPC who are treated with IMRT may obtain satisfactory long-term survival outcomes. The additional chemotherapy cannot significantly increase survival; however, it may remarkably increase treatment-associated acute toxic reactions.