Theoretical and Experimental Study on the Thermal Insulation Performance of the Roof with Water-Retained Bricks.

In this paper, the thermal insulation performance of the roof with water-retained bricks was first analyzed theoretically with respect to the thermal inertia, attenuation and delay time of the roof with water-retained bricks. Then, the experimental rig was established to carry out the experimental research on the thermal insulation performance of the roof with and without water-retained bricks on the sunny, overcast and rainy days in the summer and on the sunny day in the winter. The results showed that: (1) the surface heat storage coefficient is affected by the evaporating heat transfer of the water layer; (2) the thermal inertness, attenuation and delay time of the roof with water-retained bricks are 2.575, 21 and 6.94 h, respectively, when the water depth is 2 cm; (3) on the sunny, overcast and rainy days in the summer, laying water-retained bricks can enhance the heat insulation performance of the roof, and can improve the thermal comfort of the loft; and (4) on the sunny day in the winter, after laying water-retained bricks, the average temperature of the loft in 24 h increases by 2.3 °C, and the temperature fluctuation of the loft decreases by 56.0%. Therefore, the thermal insulation effect is significantly improved after laying water-retained bricks on the roof from the results of both the theoretical and experimental study.

Numerical Study on Effects of Wind Speed and Space Heights on Water Evaporating Performance of Water-Retained Bricks.

Energy-saving roof renovation methods are effective ways to alleviate the urban heat island effect. In this paper, the authors propose three models of two-layer water-retained bricks, established the physical and mathematic models of the water-retained bricks, and then conducted a computational fluid dynamics (CFD) simulation on the effect of wind speed and evaporation space height on the water-evaporating performance of water-retained bricks. The results show that: (1) for the water-retained bricks with no-hole lids, macroscopic evaporation does not happen under the static wind conditions; with the increase of wind speed, the evaporating boundary layer thickness decreases, the water vapor concentration gradient in the boundary layer and the mass diffusion flux increase; (2) for the water-retained bricks with strip-hole lids, under the static wind condition, the evaporating performance of the water-retained bricks with strip-hole lids is better than that of bricks with no-hole lids; with the increase of wind speed, the evaporation of bricks with strip-hole lids is less affected by inlet airflow velocity than that of bricks with no-hole lids; (3) as for both the water-retained bricks with no-hole lids and with strip-hole lids, for a given wind speed, both the water vapor concentration gradient and the mass diffusion flux decrease as the evaporation space increases.

A xanthene-based fluorescent probe for detection of peroxynitrite in living cells and zebrafish.

Peroxynitrite (ONOO-) is one of quite critical reactive oxygen species that acts critical roles in a number of diverse biological functions and pathological events. Notably, excessive ONOO- will lead to sorts of diseases. Thus, monitoring of endogenous ONOO- levels will be conducive to exploring the physiological activities and functions of ONOO-. Here, a simple turn-on fluorescent probe named DMX is reported using CN bond as the ONOO- recognition site and xanthene as the fluorophore. DMX possessed a good linear dependence with ONOO- concentration (0-9 µM), highly sensitive detection (DL = 37 nM), and excellent selectivity towards ONOO-. What is more, the biological experiments reveal that DMX is able to be utilized to track exogenous/endogenous ONOO- employing confocal laser scanning microscopy. Visualization of ONOO- in zebrafish was also successfully conducted, suggesting that DMX might be used to study ONOO- roles in vivo. We believe that DMX will have potential for exploring the pivotal role of ONOO- during all sorts of physiological and pathological activities.

A deep red ratiometric fluorescent probe for accurate detection of peroxynitrite in mitochondria.

Peroxynitrite (ONOO-) is widespread within living organisms and has been implicated in many physiological and pathological processes. Since ONOO- is mainly produced in mitochondria, accurate detection of ONOO- in mitochondria can help us understand its specific mechanism of action in the organism. Rather than single-wavelength emissive mitochondrial probes, ratiometric fluorescent probes with longer emission wavelength, large emission shift, and specific mitochondrial targeting properties are more likely to obtain a more accurate ONOO- content in mitochondria. To further avoid the interference by cytoplasmic ONOO-, we constructed a fluorescent probe MXMP with deep red emission and ratio properties, and it will be forbidden to enter the mitochondria after oxidation. In addition to its excellent selectivity and sensitivity, it shifted its fluorescence emission by up to 130 nm, with a detection limit of 84 nM.

A Randomized Phase I Study of Abemaciclib in Chinese Patients with Advanced and/or Metastatic Cancers.

BACKGROUND: Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, is approved in combination with endocrine therapy or as monotherapy for hormone receptor-positive and human epidermal growth factor receptor-2-negative (HR+/HER2-) advanced breast cancer outside of China. OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetic (PK) profile of abemaciclib in Chinese patients with advanced and/or metastatic cancers. PATIENTS AND METHODS: A multicenter, open-label, phase I trial of abemaciclib in Chinese patients with advanced and/or metastatic cancers was conducted. Patients were randomized (1:1) to oral abemaciclib 150 or 200 mg every 12 h on a 28-day cycle. Safety analyses (primary outcome) included all patients receiving at least one dose of abemaciclib. PK and antitumor activity were also assessed. RESULTS: Of the 26 patients randomized, 25 received abemaciclib 150 mg (n = 12) or 200 mg (n = 13). All 25 patients reported ≥ 1 treatment-emergent adverse event (TEAE). The majority of TEAEs were Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or 2 in severity. The most frequent TEAEs of Grade ≥ 3 were neutropenia (32%) and thrombocytopenia (24%). Four patients (16%) discontinued treatment due to AEs. Abemaciclib exhibited slow absorption and clearance at single dose, with maximum concentrations achieved after around 6 h and an elimination half-life of approximately 24 h. No complete response was observed, two patients (8%) achieved partial response, with one confirmed responder, and the disease control rate was 68% (n = 17). CONCLUSIONS: Abemaciclib was well tolerated and the safety and PK profiles in Chinese patients were comparable to those previously reported in non-Chinese populations. Preliminary antitumor activity was observed. CLINICALTRIALS. GOV IDENTIFIER: NCT02919696.

Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized, double-blind, Phase III trial.

Background: FRESCO study demonstrated efficacy and safety of fruquintinib in metastatic colorectal cancer patients. Impact of prior targeted therapy (PTT) on efficacy and safety of fruquintinib was evaluated. Materials & methods: In this subgroup analysis of FRESCO trial, patients were divided into PTT and non-PTT subgroups, and efficacy and safety of fruquintinib were assessed, respectively. Results: In non-PTT subgroup, fruquintinib significantly prolonged overall survival (OS) and progression-free survival (PFS) of patients compared with placebo. In PTT subgroup, the median OS and PFS of patients in fruquintinib arm was significantly higher than those in placebo. Treatment-emergent adverse events (TEAEs) rates were similar in both subgroups. Conclusion: Fruquintinib demonstrated clinically meaningful improvement in OS, PFS, objective response rate, and disease control rate with manageable TEAEs in both subgroups. Clinical trial registration: NCT02314819 (ClinicalTrials.gov).

Lay abstract In this analysis of the FRESCO trial, we evaluated the efficacy and safety of fruquintinib in two different groups of patients (subgroups) with metastatic colorectal cancer - patients who received prior targeted therapy (PTT) and patients who did not (non-PTT). Of the 278 patients treated with fruquintinib, 111 patients received PTT. Patients treated with fruquintinib had longer overall survival and it took longer for their disease to worsen in both PTT and non-PTT subgroups compared with placebo. Patients in both subgroups treated with fruquintinib showed measurable reduction in their tumor size and disease control with similar side effects in patients of both the subgroups. These results suggest that fruquintinib is safe and effective in patients with metastatic colorectal cancer in both subgroups.

Safety Profile and Adverse Events of Special Interest for Fruquintinib in Chinese Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of the Phase 3 FRESCO Trial.

INTRODUCTION: In FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) trial, fruquintinib demonstrated a statistically significant and clinically meaningful overall survival benefit in Chinese patients with metastatic colorectal cancer (mCRC). However, its safety profile, including adverse events of special interest (AESIs) and treatment-emergent adverse events (TEAEs) by age, sex, and body mass index (BMI), is not well known. The present analysis evaluated the safety profile and AESIs for fruquintinib in the FRESCO trial. METHODS: In FRESCO, eligible Chinese patients were randomized (2:1) to receive fruquintinib (5 mg once daily for 3 weeks, followed by 1 week off in 28-day cycles) or placebo plus best supportive care. Treatment-related AESIs and time to first occurrence of AESIs were summarized. Treatment-related TEAEs by age, sex, and BMI were also summarized. RESULTS: A total of 266 patients (95.7%) in the fruquintinib group and 97 (70.8%) in the placebo group had at least one treatment-related TEAE; the mean relative dose intensity was 92% and 98%, respectively. In the fruquintinib group, the most common (in > 40% of patients) treatment-related AESIs were hypertension (55.4%), palmar-plantar erythrodysesthesia syndrome [known as hand-foot skin reaction (HFSR)] (49.3%), and proteinuria (42.1%). The most common treatment-related grade ≥ 3 AESIs (≥ 3% of patients) were hypertension (21.2%), HFSR (10.8%), and proteinuria (3.2%); the median time to onset of these events was 10, 21, and 20 days, respectively. Subgroup analysis by age, sex, and BMI revealed that the frequencies of treatment-related TEAEs were similar across all subgroups, and were consistent with the overall safety profile of fruquintinib. CONCLUSIONS: The most common treatment-related grade ≥ 3 AEs were hypertension, HFSR, and proteinuria. The treatment-related TEAE profile of fruquintinib in Chinese patents with mCRC was comparable among different subgroups and consistent with that reported in the overall population. TRIAL REGISTRATION: Clinical Trials identifier NCT02314819.

Iron oxides nanobelt arrays rooted in nanoporous surface of carbon tube textile as stretchable and robust electrodes for flexible supercapacitors with ultrahigh areal energy density and remarkable cycling-stability.

We report a significant advance toward the rational design and fabrication of stretchable and robust flexible electrodes with favorable hierarchical architectures constructed by homogeneously distributed α-Fe2O3 nanobelt arrays rooted in the surface layer of nanoporous carbon tube textile (NPCTT). New insight into alkali activation assisted surface etching of carbon and in-situ catalytic anisotropic growth is proposed, and is experimentally demonstrated by the synthesis of the Fe2O3 nanobelt arrays/NPCTT. The Fe2O3/NPCTT electrode shows excellent flexibility and great stretchability, especially has a high specific areal capacitance of 1846 mF cm-2 at 1 mA cm-2 and cycling stability with only 4.8% capacitance loss over 10,000 cycles at a high current density of 20 mA cm-2. A symmetric solid-state supercapacitor with the Fe2O3/NPCTT achieves an operating voltage of 1.75 V and a ultrahigh areal energy density of 176 µWh cm-2 (at power density of 748 µW cm-2), remarkable cycling stability, and outstanding reliability with no capacity degradation under repeated large-angle twisting. Such unique architecture improves both mechanical robustness and electrical conductivity, and allows a strong synergistic attribution of Fe2O3 and NPCTT. The synthetic method can be extended to other composites such as MnO nanosheet arrays/NPCTT and Co3O4 nanowire arrays/NPCTT. This work opens up a new pathway to the design of high-performance devices for wearable electronics.

Endless Pursuit: Evolution of Insulin Administration.

Diabetes mellitus is a chronic metabolic health condition affecting the steady state of blood sugar level. The usual method of administration is subcutaneous injection of insulin. There are several ways to subcutaneously inject insulin, such as syringes, insulin pens, and insulin pumps. However, subcutaneous injections of insulin can lead to discomfort, pain and local infection. This review focuses on traditional methods of insulin administration, non-invasive approaches, and new insulin therapy technologies, and the advantages and disadvantages of these approaches, as well as future development prospects are also discussed.

Change of SPARC expression after chemotherapy in gastric cancer.

OBJECTIVE: The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine (SPARC) expression changes after chemotherapy in gastric cancer (GC) is unclear. This study investigated the influence of chemotherapy on SPARC expression in GC. METHODS: Immunohistochemistry was used to analyze SPARC expression in 132 GC cases (including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy). SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the influence of chemotherapy on SPARC expression. RESULTS: SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPARC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy, gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors. CONCLUSION: SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy.

Gemcitabine plus S-1 versus cetuximab as a third-line therapy in metastatic colorectal cancer: an observational trial.

BACKGROUND AND AIM: After failure of oxaliplatin, irinotecan, and 5-fluorouracil (5-FU), there is no effective and low-cost therapy for metastatic colorectal cancer (mCRC). The purpose of this study was to assess the efficacy and safety of gemcitabine plus S-1 (GS) versus cetuximab as a third-line chemotherapy for mCRC patients. METHODS: Patients with previous failure of oxaliplatin, 5-FU, and irinotecan chemotherapy were included. The patients received GS or cetuximab until disease progression or intolerable toxicity occurred. The regimen that was selected by the patient depended on their economic ability. RESULTS: In all, 38 patients were enrolled between October 2009 and October 2012, and the patients were divided into 2 groups of 19 patients each. The median overall survival (OS) was 10 months for the GS group and 6.9 months for the cetuximab group (P = 0.047). The median progression-free survival (PFS) was 79 days and 78 days (P = 0.344), respectively. The disease control rate (DCR) was 42.11% and 47.37%, respectively (P = 0.985). The overall response rate was 0% and 10.52%, respectively (P = 0.169). Adverse events related to chemotherapy were mild to moderate. Only grade 3-4 neutropenia was found in the GS group at a rate of 21.1%. In the cetuximab group, the rash incidence rate was 89.6%, with 1 patient reaching grade 3. CONCLUSIONS: GS has benefits in OS compared with cetuximab, and is a promising and safe regimen as a third-line chemotherapy for oxaliplatin- and irinotecan-refractory mCRC with good performance status for mCRC patients.

The pretreatment platelet and plasma fibrinogen level correlate with tumor progression and metastasis in patients with pancreatic cancer.

Cancer patients frequently present with activated coagulation pathways and thrombocytosis, which are potentially associated with tumor progression and prognosis. However, the prognostic value of abnormal plasma fibrinogen and platelet levels for the treatment of pancreatic cancer is unclear. The purpose of our study was to evaluate the prognostic value of plasma fibrinogen and platelet levels in pancreatic cancer, and to devise a prognostic model to identify the patients with greatest risk for a poor overall survival. One hundred and twenty-five patients diagnosed with pancreatic ductal adenocarcinoma in our hospital between May 2000 and June 2005 were included in this study. The plasma fibrinogen and platelet levels were examined before treatment and analyzed along with patient clinicopathological parameters and overall survival. The foundation of prognostic model was based on the risk factors according to the Cox proportional hazard model. The incidence of hyperfibrinogenemia and thrombocytosis was 24.8% (31/125) and 15.2% (19/125), respectively. The mean fibrinogen concentration differed significantly between the early (I/II) and late (III/IV) stage patients (3.19 ± 0.70 vs. 3.65 ± 0.90 g/l, p = 0.008). Patients with a higher concentration of plasma fibrinogen and platelets had a worse prognosis (p < 0.05). There also existed a significant correlation between higher fibrinogen/platelet levels and distant organ metastasis (p < 0.05, respectively). Bivariate correlation analysis showed that plasma fibrinogen levels correlated significantly with platelet levels (p = 0.000). Multivariate analysis revealed that pretreatment plasma fibrinogen levels (p = 0.027), tumor stage (p = 0.026) and distant metastasis (p = 0.027) were independent prognostic factors. The median survival time for the low-, intermediate-, and high-risk groups was 9.6 months (95% CI 6.2-13.0), 3.8 months (95% CI 2.3-5.3), and 2.3 months (95% CI 0.9-3.7), respectively (p = 0.000). Pretreatment plasma fibrinogen and platelet levels closely correlated with tumor progression, metastasis and overall survival in pancreatic cancer. The foundation of prognostic model may help us identify the greatest risk populations with pancreatic cancer.

Gemcitabine sensitivity factors, hENT1 and RRM1 as potential prognostic biomarker for advanced biliary tract cancer.

BACKGROUND AND AIMS: Biliary tract caner (BTC) is one of rare malignant disease with poor prognosis. Gemcitabine has been widely used as chemotherapeutic agent for advanced BTC treatment. Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1) and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of chemotherapy efficacy. The aim of present study is to determine whether hENT1 and RRM1 could be used as the biomarkers to assess the efficacy of chemotherapy and predict survival in patients with advanced BTC. METHODS: The analysis was performed on samples from 44 patients with unresectable or recurrent BTC who were treated with gemcitabine as first-line therapy. We determined levels of hENT1 and RRM1 with immunohistochemistry (IHC). Also, its prognostic and predictive role on tumor response and several clinical factors for survival were evaluated with Kaplan-Meier or Cox analysis. RESULTS: The patients who were clinical benefit (partial response [PR] or stable disease [SD]) had high level of hENT1 (P = 0.046) and low level of RRM1 (P = 0.033). Moreover, hENT1 expression was a significant factor for progression free survival (PFS) (P = 0.005) and overall survival (OS) (P = 0.048) in Cox univariate analysis. Also, hENT1 was an independent prognostic factor of OS based on Cox multivariate analysis (P = 0.005). CONCLUSIONS: The expression of hENT1 and RRM1 was associated with gemcitabine efficacy. hENT1 was one of reliable predictive marker of survival in patients with advanced BTC patients.

Comparison of epidermal growth factor receptor mutation statuses in tissue and plasma in stage I-IV non-small cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations play essential roles in the treatment of non-small cell lung cancer (NSCLC) patients using EGFR tyrosine kinase inhibitors. Detection of EGFR mutations in blood cell-free DNA (cfDNA) seems promising. However, the mutation status in the plasma/serum is not always consistent with that in the tissues. OBJECTIVES: The aims of this study were to compare the mutation statuses in plasma to those in tissues and thus to determine the specific subgroups of NSCLC patients who may be the best candidates for EGFR mutation analyses using blood cfDNA. METHODS: A total of 111 pairs of tissue and plasma samples were collected. Mutant-enriched PCR and sequencing analyses were performed to detect EGFR exon 19 deletions and exon 21 L858R mutations. RESULTS: Mutations were discovered in 43.2% (48/111) of the patients. The overall rate of consistency of the EGFR mutation statuses for the 111 paired plasma and tissue samples was 71.2% (79/111). The sensitivity and specificity rates of detecting EGFR mutations in the plasma were 35.6% (16/45) and 95.5% (63/66), respectively. The disease stage and tumor differentiation subgroups showed significantly different detection sensitivities; the sensitivity was 10% in early-stage patients and 56% in advanced-stage patients (p = 0.0014). For patients with poorly differentiated tumors, the sensitivity was 77.8%, which was significantly different from those with highly differentiated (20%; p = 0.0230) and moderately differentiated tumors (19%; p = 0.0042). CONCLUSION: Blood analyses for EGFR mutations may be effectively used in advanced-stage patients or patients with poorly differentiated tumors.

[Comparison of EGFR mutation status in paired pre- and post-chemotherapy serum for advanced pulmonary adenocarcinoma].

BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) with mutations in the epidermal growth factor receptor (EGFR) is a distinct subgroup of NSCLC, which is particularly responsive to EGFR tyrosine kinase inhibitors (TKIs). The aim of this study is to detect EGFR mutations in paired serum of pre- and post-chemotherapy from advanced pulmonary adenocarcinoma patients to evaluate impact of chemotherapy on EGFR mutation status. METHODS: Magnetic beads were used for DNA extraction from paired serum of pre- and post-chemotherapy of 33 advanced pulmonary adenocarcinoma patients. The EGFR exon 19 and 21 were amplified by mutant-enriched nested PCR and analyzed by direct sequencing. RESULTS: EGFR mutations were detected in 39.4% (13/33) and 54.5% (18/33) serum samples of pre- and postchemotherapy, respectively. The EGFR mutation status was consistent in 54.5% (18/33) patients. Among 15 discordant cases, 10 changed from pre-chemo wild-type to post-chemo mutant-type status, while 5 from pre-chemo mutant-type to post-chemo wild-type status. CONCLUSIONS: Chemotherapy may have influence on serum EGFR mutation status in advanced adenocarcinoma patients.