Magnesium alleviates extracellular histone-induced apoptosis and defective bacterial phagocytosis in macrophages by regulating intracellular calcium signal.

Extracellular histones have been determined as important mediators of sepsis, which induce excessive inflammatory responses in macrophages and impair innate immunity. Magnesium (Mg2+), one of the essential nutrients of the human body, contributes to the proper regulation of immune function. However, no reports indicate whether extracellular histones affect survival and bacterial phagocytosis in macrophages and whether Mg2+ is protective against histone-induced macrophage damage. Our clinical data revealed a negative correlation between circulating histone and monocyte levels in septic patients, and in vitro experiments confirmed that histones induced mitochondria-associated apoptosis and defective bacterial phagocytosis in macrophages. Interestingly, our clinical data also indicated an association between lower serum Mg2+ levels and reduced monocyte levels in septic patients. Moreover, in vitro experiments demonstrated that Mg2+ attenuated histone-induced apoptosis and defective bacterial phagocytosis in macrophages through the PLC/IP3R/STIM-mediated calcium signaling pathway. Importantly, further animal experiments proved that Mg2+ significantly improved survival and attenuated histone-mediated lung injury and macrophage damage in histone-stimulated mice. Additionally, in a cecal ligation and puncture (CLP) + histone-induced injury mouse model, Mg2+ inhibited histone-mediated apoptosis and defective phagocytosis in macrophages and further reduced bacterial load. Overall, these results suggest that Mg2+ supplementation may be a promising treatment for extracellular histone-mediated macrophage damage in sepsis.

Shexiang Baoxin Pill treats acute myocardial infarction by promoting angiogenesis via GDF15-TRPV4 signaling.

Angiogenesis has been considered a pivotal strategy for treating ischemic heart disease. One possible approach, the Shexiang Baoxin Pill (MUSKARDIA), has been noted to promote angiogenesis, but its underlying mechanism is still largely unknown. We aimed to determine the effects of MUSKARDIA on acute myocardial infarction (AMI), as well as the underlying mechanistic bases. AMI was induced in rats, using left anterior descending coronary arterial occlusion, and either 6 (low) or 12 (high-dose) mg/kg/day of MUSKARDIA was administered for 56 days. We found that MUSKARDIA improved cardiac function and counteracted against adverse remodeling among AMI rats, which most likely is due to it promoting angiogenesis. Transcriptome analysis by RNA-sequencing found that MUSKARDIA up-regulated cardiac pro-angiogenic genes, particularly growth differentiation factor 15 (GDF15), which was confirmed by RT-qPCR. This up-regulation was also correlated with elevated serum GDF15 levels. In vitro analyses with human umbilical vein endothelial cells found that increased GDF15, stimulated by MUSKARDIA, resulted in enhanced cell migration, proliferation, and tubular formation, all of which were reversed after GDF15 knockdown using a lentiviral vector. Gene Ontology, as well as Kyoto Genes and Genomes enrichment analyses identified calcium signaling pathway as a major contributor to these outcomes, which was verified by Western blot and Cal-590 AM loading showing that transient receptor potential cation channel subfamily V member 4 protein (TRPV4) and intracellular Ca2+ levels increased in accordance with MUSKARDIA-induced GDF15 up-regulation, and decreased with GDF15 knock-down. Therefore, MUSKARDIA may exert its cardioprotective effects via stimulating the GDF15/TRPV4/calcium signaling/angiogenesis axis.

Potential benefits of vitamin D for sepsis prophylaxis in critical ill patients.

Background: Vitamin D deficiency is common in critically ill patients with suspected infection and is strongly associated with the predisposition of sepsis and a poor prognosis. The effectiveness of vitamin D supplementation for preventing sepsis remains unclear. This retrospective cohort study investigated the effect of vitamin D supplementation on sepsis prophylaxis in critically ill patients with suspected infection. Methods: This retrospective cohort study included 19,816 adult patients with suspected infection in intensive care units (ICU) from 2008 to 2019 at the Beth Israel Deaconess Medical Center, Boston, USA. The included patients were divided into the vitamin D cohort or non-vitamin D cohort according to vitamin D administration status. The primary outcomes were the incidence of sepsis in ICU. The secondary outcomes included 28-day all-cause mortality, length of ICU and hospital stay and the requirements of vasopressors or mechanical ventilation. A propensity score matching cohort was used to test the differences in primary and secondary outcomes between groups. Results: The results showed that vitamin D supplementation demonstrated a lower risk of sepsis (odd ratio 0.46; 95% CI 0.35-0.60; P < 0.001) and a lower risk of new mechanical ventilation requirement (odd ratio 0.70; 95% CI 0.53-0.92; P = 0.01), but no significant difference in the risk of 28-day mortality was observed (hazard ratio 1.02; 95% CI 0.77-1.35; P = 0.89). In the sensitive analysis, among the patients who suspected infection within 24 h before or after ICU admission, a lower risk of sepsis and a lower percentage of new mechanical ventilation also were detected in the vitamin D cohort. Conclusion: Vitamin D supplementation may have a positively prophylactic effect on sepsis in critically ill patients with suspected infection.

Combination therapy of sorafenib and drug-eluting bead transarterial chemoembolization for advanced hepatocellular carcinoma with and without hepatic arteriovenous shunt.

BACKGROUND: To compare the efficacy and safety of combination therapy with sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in advanced hepatocellular carcinoma (HCC) with or without hepatic arteriovenous shunt (HAVS). METHODS: This retrospective, single-center study enrolled 59 advanced HCC patients treated with combination therapy, of whom 33 (55.9%) patients had HAVS. Tumor response according to the mRECIST criteria was evaluated based on the CT images 1 month after TACE, and changes in the arterial enhancement ratio (AER) of tumors and portal vein tumor thrombosis were also documented. Time-to-progression (TTP), overall survival (OS), and prognostic factors were analyzed. Safety was evaluated with the incidence of TACE-related complications within 6 weeks after TACE. RESULTS: The tumor response between the two groups showed no significant difference in the objective response rate (69.2% in the group without HAVS vs 60.6% in the group with HAVS, p = 0.492) or disease control rate (92.3% vs 87.9%, p = 0.685). The two groups showed comparable TTP (4.23 vs 2.33 months, p = 0.235) and OS (12.77 vs 12.97 months, p = 0.910). A drop in the AER of tumors of more than 20% on post-TACE CT independently predicted better OS. With regard to safety, there was no significant difference between the two groups. CONCLUSION: For advanced HCC, combination therapy had equal efficacy and safety in patients with HAVS compared to those without HAVS, indicating that DEB-TACE is an optional and effective treatment in these patients.

Addition of topical airway anaesthesia to conventional induction techniques to reduce haemodynamic instability during the induction period in patients undergoing cardiac surgery: protocol for a randomised controlled study.

INTRODUCTION: The aim of this prospective study is to evaluate the effects of combining topical airway anaesthesia with intravenous induction on haemodynamic variables during the induction period in patients undergoing cardiac surgery. METHODS AND ANALYSIS: This randomised, double-blind, controlled, parallel-group, superiority study from 1 March 2021 to 31 December 2021 will include 96 participants scheduled for cardiac surgery. Participants will be screened into three blocks (ASA II, ASA III, ASA IV) according to the American Society of Anesthesiologists (ASA) grade and then randomly allocated into two groups within the block in a 1:1 ratio. Concealment of allocation will be maintained using opaque, sealed envelopes generated by a nurse according to a computer-generated randomisation schedule. In addition to general intravenous anaesthetics, participants will receive supraglottic and subglottic topical anaesthesia. Changes in arterial blood pressure and heart rate in both groups will be recorded by an independent investigator at the start of anaesthesia induction until the skin incision. If vasopressors are used during this period, the frequency, dosage and types of vasopressors will be recorded. The incidence and severity of participants' postoperative hoarseness and sore throat will also be assessed. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Qianfoshan Hospital of Shandong Province (registration number: YXLL-KY-2021(003)). The results will be disseminated through a peer-reviewed publication and in conferences or congresses. TRIAL REGISTRATION NUMBER: NCT04744480.

Acupoint Injection Decreases Anesthetic Cosumption during Combined Spinal-Epidural and Patient-Controlled Epidural Labor Analgesia.

OBJECTIVE: To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia. METHODS: A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention. RESULTS: The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05). CONCLUSION: Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).

Acupoint Injection Decreases Anesthetic Cosumption during Combined Spinal-Epidural and Patient-Controlled Epidural Labor Analgesia / 中国结合医学杂志

OBJECTIVE@#To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia.@*METHODS@#A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention.@*RESULTS@#The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05).@*CONCLUSION@#Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).

Comparative transcriptome and DNA methylation analysis in temperature-sensitive genic male sterile wheat BS366.

BACKGROUND: Known as the prerequisite component for the heterosis breeding system, the male sterile line determines the hybrid yield and seed purity. Therefore, a deep understanding of the mechanism and gene network that leads to male sterility is crucial. BS366, a temperature-sensitive genic male sterile (TGMS) line, is male sterile under cold conditions (12 °C with 12 h of daylight) but fertile under normal temperature (20 °C with 12 h of daylight). RESULTS: During meiosis, BS366 was defective in forming tetrads and dyads due to the abnormal cell plate. During pollen development, unusual vacuolated pollen that could not accumulate starch grains at the binucleate stage was also observed. Transcriptome analysis revealed that genes involved in the meiotic process, such as sister chromatid segregation and microtubule-based movement, were repressed, while genes involved in DNA and histone methylation were induced in BS366 under cold conditions. MethylRAD was used for reduced DNA methylation sequencing of BS366 spikes under both cold and control conditions. The differentially methylated sites (DMSs) located in the gene region were mainly involved in carbohydrate and fatty acid metabolism, lipid metabolism, and transport. Differentially expressed and methylated genes were mainly involved in cell division. CONCLUSIONS: These results indicated that the methylation of genes involved in carbon metabolism or fatty acid metabolism might contribute to male sterility in BS366 spikes, providing novel insight into the molecular mechanism of wheat male sterility.

[L-carnitine-astaxanthin compound nutrients for the treatment of idiopathic oligospermia and asthenozoospermia: A multicenter clinical observation].

OBJECTIVE: To investigate the clinical effects of the L-carnitine-astaxanthin compound nutrients Menglankang (MLK) on idiopathic oligospermia (OS) and asthenospermia (AS). METHODS: This study included 73 cases of OS and 220 cases of AS treated with MLK once a bag, bid, for 3 successive months. Before and at 1, 2 and 3 months after treatment, we obtained and analyzed the semen parameters and sperm DNA fragmentation index (DFI) of the patients. RESULTS: Compared with the baseline, the OS patients showed remarkable increases after 1 and 2 months of treatment in the semen volume (ï¼»3.07 ± 1.47ï¼½ vs ï¼»3.26 ± 1.26ï¼½ and ï¼»3.30 ± 1.28ï¼½ ml), sperm concentration (ï¼»10.96 ± 6.09ï¼½ vs ï¼»16.74 ± 11.15ï¼½ and ï¼»17.56 ± 9.92ï¼½ ×106/ml, P < 0.05), total sperm count (ï¼»29.78 ± 17.48ï¼½ vs ï¼»52.98 ± 32.07ï¼½ and ï¼»57.67 ± 36.98ï¼½ ×106, P < 0.05) and the percentages of progressively motile sperm (PMS) (ï¼»39.8 ± 11.66ï¼½% vs ï¼»45.3 ± 14.03ï¼½% and ï¼»46.42 ± 10.69ï¼½%, P < 0.05) and morphologically normal sperm (MNS) (ï¼»1.71 ± 1.07ï¼½% vs ï¼»1.79 ± 0.91ï¼½% and ï¼»1.84 ± 0.96ï¼½%), and so did the AS patients in PMS (ï¼»19.23 ± 8.32ï¼½% vs ï¼»25.46 ± 13.86ï¼½% and ï¼»27.33 ± 12.88ï¼½%, P < 0.05). After 3 months of medication, the OS patients exhibited even more significant increases in the semen volume (ï¼»3.63 ± 1.39ï¼½ ml) (P < 0.05), sperm concentration (ï¼»20.56 ± 14.7ï¼½ ×106/ml) (P < 0.05), total sperm count (ï¼»66.35 ± 55.91ï¼½ ×106) (P < 0.05), PMS (ï¼»49.24 ± 13.45ï¼½%) (P < 0.05) and MNS (ï¼»2.59 ± 0.93ï¼½%) (P < 0.05), and so did the AS patients in the semen volume (ï¼»3.27 ± 1.42ï¼½ vs ï¼»3.85 ± 1.59ï¼½ ml, P < 0.05), PMS (ï¼»29.11 ± 13.58ï¼½%) (P < 0.05) and NMS (ï¼»2.01 ± 1.14ï¼½% vs ï¼»2.57 ± 1.15ï¼½%, P < 0.05). In comparison with the baseline, the sperm DFI was not significantly improved at 1 month after treatment, but remarkably decreased at 2 and 3 months in the OS patients (ï¼»25.87 ± 13.76ï¼½% vs ï¼»18.66 ± 10.83ï¼½% and ï¼»16.48 ± 11.46ï¼½%, P < 0.05) and the AS patients as well (ï¼»26.40 ± 12.28ï¼½% vs ï¼»19.35 ± 11.54ï¼½% and ï¼»15.32 ± 10.89ï¼½%, P < 0.05). CONCLUSIONS: The L-carnitine-astaxanthin compound nutrients Menglankang can significantly improve the semen quality of the patients with idiopathic oligospermia or asthenospermia.

Comprehensive analysis of formin gene family highlights candidate genes related to pollen cytoskeleton and male fertility in wheat (Triticum aestivum L.).

BACKGROUND: Formin, a highly conserved multi-domain protein, interacts with microfilaments and microtubules. Although specifically expressed formin genes in anthers are potentially significant in research on male sterility and hybrid wheat breeding, similar reports in wheat, especially in thermo-sensitive genic male sterile (TGMS) wheat, remain elusive. RESULTS: Herein, we systematically characterized the formin genes in TGMS wheat line BS366 named TaFormins (TaFHs) and predicted their functions in inducing stress response. In total, 25 TaFH genes were uncovered, majorly localized in 2A, 2B, and 2D chromosomes. According to the neighbor-joining (NJ) method, all TaFH proteins from wheat and other plants clustered in 6 sub-groups (A-F). The modeled 3D structures of TaFH1-A/B, TaFH2-A/B, TaFH3-A/B and TaFH3-B/D were validated. And different numbers of stress and hormone-responsive regulatory elements in their 1500 base pair promoter regions were contained in the TaFH genes copies. TaFHs had specific temporal and spatial expression characteristics, whereby TaFH1, TaFH4, and TaFH5 were expressed highly in the stamen of BS366. Besides, the accumulation of TaFHs was remarkably lower in a low-temperature sterile condition (Nanyang) than fertile condition (Beijing), particularly at the early stamen development stage. The pollen cytoskeleton of BS366 was abnormal in the three stages under sterile and fertile environments. Furthermore, under different stress levels, TaFHs expression could be induced by drought, salt, abscisic acid (ABA), salicylic acid (SA), methyl jasmonate (MeJA), indole-3-acetic acid (IAA), polyethylene glycol (PEG), and low temperature. Some miRNAs, including miR167, miR1120, and miR172, interacts with TaFH genes; thus, we constructed an interaction network between microRNAs, TaFHs, phytohormone responses, and distribution of cytoskeleton to reveal the regulatory association between upstream genes of TaFH family members and sterile. CONCLUSIONS: Collectively, this comprehensive analysis provides novel insights into TaFHs and miRNA resources for wheat breeding. These findings are, therefore, valuable in understanding the mechanism of TGMS fertility conversion in wheat.

Uracil-tegafur vs fluorouracil as postoperative adjuvant chemotherapy in Stage II and III colon cancer: A nationwide cohort study and meta-analysis.

ABSTRACT: We conducted a population-based cohort study enrolling patients with Stage II and III colon cancer receiving postoperative adjuvant chemotherapy with uracil and tegafur (UFT) or fluorouracil (5-FU) from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the current study were disease-free survival (DFS) and overall survival (OS). Hazard ratios (HRs) were calculated by multivariate Cox proportional hazard regression models. We compared our effectiveness results from the literature by meta-analysis, which provided the best evidence. Severe adverse events were compared in meta-analysis of reported clinical trials. In the nationwide cohort study, UFT (14,486 patients) showed DFS similar to postoperative adjuvant chemotherapy (adjusted HR 1.037; 95% confidence interval [CI] 0.954-1.126; P = .397) and OS (adjusted HR 0.964; 95% CI 0.891-1.041; P = .349) compared with the 5-FU (866 patients). Our meta-analysis confirmed the similarity of effectiveness and found the incidence of leucopaenia was statistically significantly reduced in UFT (risk ratio 0.12; 95% CI 0.02-0.67; I2 = 0%). Through our analysis, we have confirmed that UFT is a well-tolerated adjuvant therapy choice, and has similar treatment efficacy as 5-FU in terms of DFS and OS in patients with Stage II and III colon cancer.

Antiproliferative effect of 2-Hydroxy-6-tridecylbenzoic acid from ginkgo biloba sarcotestas through the aryl hydrocarbon receptor pathway in triple-negative breast cancer cells.

This study aims to isolate the potential antiproliferative and cytotoxic compounds from ginkgo biloba sarcotestas (GBS) and investigates the underlying mechanism in human MDA-MB-231 and mouse 4T-1 triple-negative breast cancer cells. Our results showed that 2-Hydroxy-6-tridecylbenzoic acid was isolated by cytotoxicity-guided fractionation where different fractions were assessed using MTT assay against MDA-MB-231 and 4T-1 cells. Colony formation assay showed that 2-Hydroxy-6-tridecylbenzoic acid significantly inhibited cell proliferation. The inhibition was associated with the enhancement of cytochrome P450 (CYP) 1B1 expression in a dose- and time-dependent manner and no significant change of CYP1A1 expression by qPCR and Western blot assays in MDA-MB-231 and 4T-1 cells. The mechanism was further demonstrated by the activation of aryl hydrocarbon receptor (AhR) pathway with the upregulation of AhR, AhR nuclear translocator (ARNT) and AhR-dependent xenobiotic response elements (XRE) activity. These findings may have implications for development of anticancer agents containing 2-Hydroxy-6-tridecylbenzoic acid as functional additives.

Using a mixture of wastewater and seawater as the growth medium for wastewater treatment and lipid production by the marine diatom Phaeodactylum tricornutum.

This study was conducted to evaluate the potential of the marine diatom Phaeodactylum tricornutum in nutrient removal coupled with biodiesel production using different ratios of mixed municipal wastewater (MW) and seawater (SW) as the growth medium. The results indicated that P. tricornutum exhibited high nutrient removal efficiency with the ratios of MW: SW = 1:1 and MW: SW = 2:1, e.g. 87.7-89.9% for chemical oxygen demand (COD), 82.2-86.7% for total nitrogen (TN), 96.0-97.0% for total phosphorus, and 76.9-84.2% for ammonium (NH3-N). Significantly higher biomass and lipid productivity were obtained with aeration. The highest lipid productivity of P. tricornutum was 54.76 mg/L/day, which was obtained with a two-step cultivation using the ratio of MW: SW = 1:1 by diluting half of the mixture and bubbling with 5% CO2 during the second step. These results suggested that the marine diatom P. tricornutum exhibited great potential for using mixed wastewater for wastewater treatment and biodiesel production.

[Effect of Electroacupuncture Stimulation of Heart and Lung Meridians on Expression of Myocardial HCN 2 in Acute Myocardial Ischemia Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of Heart and Lung meridians on the expression of hyperpolarization-activated cyclic nucleotide gated potassium channel 2 (HCN 2) mRNA and protein in the myocar-dium of the left ventricle in acute myocardial ischemia (AMI) rats, so as to underlying its mechanism in improving ischemic myocardial injury. METHODS: A total of 120 male SD rats were randomly divided into normal control, model, EA-Heart Meridian (HT) and EA-Lung Meridian (LU) groups (n＝30 rats in each group). The AMI model was established by occlusion of the anterior descending branch of coronary artery. EA (1 mA, 10 Hz) was applied to bilateral "Shenmen" (HT 7) or "Taiyuan" (LU 9) and the spot about 1 mm apart from the HT 7 or LU 9 on the axopetal end for 15 min on the second day after modeling, once a day for 7 days. The left ventricular myocardium tissue was sampled for determining the expression levels of HCN 2 mRNA and protein with qPCR and Western blot, separately. RESULTS: After AMI, both HCN 2 mRNA and protein expression levels in the model group were significantly decreased in comparison with the normal control group (P<0.01). Following EA intervention, the expression levels of HCN 2 mRNA and protein expressions were significantly up-regulated relevant to the model group (P<0.01)．The effects were more obvious in the EA-HT group than in the EA-LU group, and the expression levels were higher in the left ventricular myocardium tissue sampled on the next day after the treatment than those in the tissue sampled immediately after the treatment (P<0.01). CONCLUSION: Both EA stimulation of Heart Meridian and Lung Meridian can improve the expression of HCN 2 mRNA and protein in the myocardium in AMI rats, which existing a delayed effect and meridian specificity.

[Effect of Different Concentrations of Moxa-smoke on Lung Function and TNF-α and IL-1 ß Levels in Serum and Lung Tissues in Normal Rats].

OBJECTIVE: To study the effect of moxa-smoke inhaling on the respiratory system, so as to provide experimental data and theoretical basis for evaluating the safety of moxa-smoke inhaling during moxibustion treatment. METHODS: A total of 48 SD rats were randomized into control, low, medium and high moxa-smoke-concentration groups (n＝12 in each group). The low, medium and high concentrations of smoke were controlled in (0.11±0.05) mg/m3, (0.23±0.05) mg/m3 and (0.53±0.05) mg/m3 respectively in each of 3 glass boxes (with reference to the level of PM 2.5). The smoking was conducted 4 hours each time, twice a day for 100 days. The normal group did not receive any moxa-smoke inhaling. The histopathological changes of lung and bronchial tissues were detected by H．E. stainning, and the contents of TNF-α and IL-1 ß of plasma, bronchoalveolar la-vage fluid (BALF) and lung tissue detected by ELISA. The levels of forced vital capacity (FVC), forced expiratory volume (FEV), FEV 0.3/FVC (0.3＝ the 0.3rd second), maximal mid-expiratory flow rate(MMEF), peak expiratory flow(PEF) were detected by animal pulmonary function analysis system. RESULTS: After 100 days' moxa-smoke inhaling, the contents of TNF-α in the plasma, BALF and lung tissues and IL-1 ß in the lung tissue of the low, medium and high concentration moxa-smoke groups, and IL-1 ß in the plasma and BALF of the medium and high concentration groups were significantly increased relevant to the control group (P<0.05, P<0.01). H．E. stain showed various inflammatory changes in the lungs and trachea tissues, including obvious fusion of pulmonary alveoli, lymphocyte infiltration, increase of capillary permeability, red blood cell exudation, etc. in the high concentration group, these situations were milder in the medium concentration group and were not obvious in the low concentration group. Compared with the control group, there were no significant changes in the FVC, FEV, FEV 0.3/FVC, MMEF and PEF of lung function in the three concentration groups (P> 0.05)．. CONCLUSION: Long term inhalation of high concentration of moxa-smoke may lead to inflammatory injury in the lung and bronchial tissues but has no significant effect on the respiratory function in rats. Nevertheless, a good air-ventilation during moxibustion in a treatment room is necessary.

Triclosan: A review on systematic risk assessment and control from the perspective of substance flow analysis.

Triclosan (TCS) is a broad spectrum antibacterial agent mainly used in Pharmaceutical and Personal Care Products. Its increasing use over recent decades have raised its concentration in the environment, with commonly detectable levels found along the food web-from aquatic organisms to humans in the ecosystem. To date, there is shortage of information on how to investigate TCS's systematic risk on exposed organisms including humans, due to the paucity of systematic information on TCS flows in the anthroposphere. Therefore, a more holistic approach to mass flow balancing is required, such that the systematic risk of TCS in all environmental matrices are evaluated. From the perspective of Substance Flow Analysis (SFA), this review critically summarizes the current state of knowledge on TCS production, consumption, discharge, occurrence in built and natural environments, its exposure and metabolism in humans, and also the negative effects of TCS on biota and humans. Recent risk concerns have mainly focused on TCS removal efficiencies and metabolism, but less attention is given to the effect of mass flows from source to fate during risk exposure. However, available data for TCS SFA is limited but SFA can derive logical systematic information from limited data currently available for systematic risk assessment and reduction, based on mass flow analysis. In other words, SFA tool can be used to develop a comprehensive flow chart and indicator system for the risk assessment and reduction of TCS flows in the anthroposphere, thereby bridging knowledge gaps to streamline uncertainties related to policy-making on exposure pathways within TCS flow-lines. In the final analysis, specifics on systematic TCS risk assessment via SFA, and areas of improvement on human adaptation to risks posed by emerging contaminants are identified and directions for future research are suggested.

Archaeal community in a human-disturbed watershed in southeast China: diversity, distribution, and responses to environmental changes.

The response of freshwater bacterial community to anthropogenic disturbance has been well documented, yet the studies of freshwater archaeal community are rare, especially in lotic environments. Here, we investigated planktonic and benthic archaeal communities in a human-perturbed watershed (Jiulong River Watershed, JRW) of southeast China by using Illumina 16S ribosomal RNA gene amplicon sequencing. The results of taxonomic assignments indicated that SAGMGC-1, Methanobacteriaceae, Methanospirillaceae, and Methanoregulaceae were the four most abundant families in surface waters, accounting for 12.65, 23.21, 18.58 and 10.97 % of planktonic communities, whereas Nitrososphaeraceae and Miscellaneous Crenarchaeotic Group occupied more than 49 % of benthic communities. The compositions of archaeal communities and populations in waters and sediments were significantly different from each other. Remarkably, the detection frequencies of families Methanobacteriaceae and Methanospirillaceae, and genera Methanobrevibacter and Methanosphaera in planktonic communities correlated strongly with bacterial fecal indicator, suggesting some parts of methanogenic Archaea may come from fecal contamination. Because soluble reactive phosphorus (SRP) and the ratio of dissolved inorganic nitrogen to SRP instead of nitrogen nutrients showed significant correlation with several planktonic Nitrosopumilus- and Nitrosotalea-like OTUs, Thaumarchaeota may play an unexplored role in biogeochemical cycling of river phosphorus. Multivariate statistical analyses revealed that the variation of α-diversity of planktonic archaeal community was best explained by water temperature, whereas nutrient concentrations and stoichiometry were the significant drivers of ß-diversity of planktonic and benthic communities. Taken together, these results demonstrate that the structure of archaeal communities in the JRW is sensitive to anthropogenic disturbances caused by riparian human activities.

RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704.

PURPOSE: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. METHODS AND MATERIALS: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. RESULTS: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23, P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70, P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63, P=.21). CONCLUSIONS: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.

Initial Experience of Sorafenib Neoadjuvant Therapy Combined with Retroperitoneoscopy in Treating T2 Large Renal Carcinoma.

OBJECTIVES: To investigate the safety and feasibility of sorafenib neoadjuvant therapy combined with retroperitoneoscopic radical nephrectomy (RRN) in treating T2 large renal cell carcinoma (RCC). METHODS: Retrospectively analyzed 5 cases (2 males and 3 females, aged 52-73 years) of T2 stage large RCC who receive preoperative sorafenib targeted treatment (400 mg bid for 1-3 months) and RRN between March, 2013, and July, 2014. Patient information, therapeutic regimen, drug adverse effect, tumor changes before and after surgery, and perioperative parameters were recorded. RESULTS: During the sorafenib therapy adverse effects included 2 cases of hypertension (Grade I toxicity), 1 case of hand-foot syndrome (Grade I), and 1 case of diarrhea (Grade II), which were all tolerable for patients. CT scan and histopathological tests confirmed significant reduction in the longest dimension (LD) and medium density (MD) of the tumor after therapy as well as tumor hemorrhage, necrosis, and cystic degeneration. All 5 patients received RRN surgery successfully around 2 weeks after drug discontinuation with only 1 case of perioperative complication. CONCLUSIONS: Sorafenib neoadjuvant therapy could significantly reduce the size and aggressiveness of T2 large renal tumors, thus reducing the operative challenge and enabling patients who were previously disqualified for operation to receive surgical treatment.

Stage III Colon Cancer: The Individualized Strategy of Adjuvant Chemotherapy for Aged Under and Over 70.

BACKGROUND: The aim of this study was to examine the specific chemoregimens selected for adjuvant therapy in the patients with stage III colon cancer. We investigated the trends in chemotherapeutic prescribing patterns and looked for adequate therapeutic setting for these patients. METHODS: 288 patients presenting with stage III colon cancer and undergoing adjuvant therapies after curative surgery for more than 3-month were enrolled between January 2006 and December 2011. Demographic characteristics and therapeutic factors were analyzed, including age, gender, histological grade, tumor sizes, tumor location, pathologic stage, performance status, serum carcinoembryonic antigen, regimens selection, interval from the operation to the start of adjuvant therapy and prolonged adjuvant therapy. Kaplan- Meier methods were utilized for drawing survival curves and Cox model was used to analyze survival, prognostic factors. RESULTS: The analysis showed that the patients aged under 70 received more intensive therapies than those aged over 70 (P<0.001). Later, advanced analysis in therapeutic factors was conducted between the patients aged under 70 and those over 70. In the patients aged under 70, significant differences in 4-year overall survival (OS) were noted between UFUR (oral tegafur-uracil plus leucovorin) groups and FOLFOX (5-FU plus oxaliplatin) [65.6% versus (vs) 89.8%, relative risk (RR) 3.780, 95% confidence interval (CI) 1.263-11.315, P = 0.017]. There were also differences in 4-year OS between these patients with and without oxaliplatin-contained regimens (92.1% vs 83.4%, respectively, RR 0.385, 95% CI 0.157-0.946, P = 0.037). In addition, the patients who received intravenous or combined therapy also had higher 4-year OS than those only received oral regimens (92.1% vs 76.6%, P = 0.077), though the finding did not reach statistical significance. In contrast to the survival benefits of above therapeutic settings for the patients aged under 70, there was less advantage in the old patients when they received intensive therapies or even oxaliplatin-contained regimens. Prolonged cycles of adjuvant therapy resulted in no significant benefit to survival rates regardless of ages. CONCLUSIONS: The adequate individualized therapeutic strategy plays an important role for stage III colon cancer. Our findings suggested that benefit of oxaliplatin-contained therapy is limited to patients aged under 70 and oral fluoropyrimidines may be an effective option for old patients. In addition, prolonged adjuvant setting is suggested to be unbeneficial for managing stage III colon cancer.