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Wei Jin,1,* Jian-Chun Duan,2,* Zhi-Jie Wang,2 Lin Lin,2 Hua Bai,2 Jie Wang,2 Li Feng1 1Department of Chinese Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie WangState Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel +86 139-1070-4669Email zlhuxi@163.comLi FengDepartment of Chinese Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel +86 186-1814-7576Email fengli663@126.comAbstract: Immunotherapy provided with checkpoint inhibitors such as the programmed cell death-1 (PD-1) receptor or its ligand-1 (PD-L1) protein has been shown to be effective for treating several types of cancer, and was recently approved for use in treating malignant melanoma, advanced non-small cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell carcinoma, liver cancer, and additional forms of cancer. However, there is little evidence concerning its effectiveness in treating thymic squamous cell carcinoma (TSCC). Here, we report two cases of refractory TSCC that were treated with PD-1 single/combination therapy in a clinical setting. The patients exhibited variable responses to therapy without any serious adverse events. In summary, our findings show that immunotherapy provided with an immuno-checkpoint inhibitor in combination with chemotherapy/anti-angiogenesis therapy can improve the treatment response of patients with refractory TSCC. Anti-PD-1 single/combination therapy may be used as a strategy for treating advanced refractory TC.Keywords: thymic carcinoma, anti-PD-1, single/combination therapy

A highly efficient and chemoselective approach for the divergent assembling of unsymmetrical hydrazines through an unprecedented intermolecular desulfurdioxidative N-N coupling is developed. This metal free protocol employs readily accessible N-arylhydroxylamines and N-sulfinylanilines to provide highly valuable hydrazine products with good reaction yields and excellent functional group tolerance under simple conditions. Computational studies suggest that the in situ generated O-sulfenylated arylhydroxylamine intermediate undergoes a retro-[2π+2σ] cycloaddition via a stepwise diradical mechanism to form the N-N bond and release SO 2 ., (© 2024 Wiley-VCH GmbH.)

In order to study the effects of clean heating measures on the concentration and source of carbonaceous aerosols in PM 2.5 in Baoding, we collected PM 2.5 samples in Baoding during the winter heating periods of 2014 and 2019. The concentrations of OC and EC in the samples were determined by using a DRI Model 2001A thermo-optical carbon analyzer.The results showed that the average values of ρ (OC) and ρ (EC) in the heating period in 2014 were 60.92 μg·m -3 and 18.15 μg·m -3 , and the average values of ρ (OC) and ρ (EC) in the heating period in 2019 were 36.63 μg·m -3 and 6.07 μg·m -3 . Compared with those in 2014, the concentrations of OC and EC decreased by 39.87% and 66.56%, respectively, in 2019; the decrease in EC was larger than that in OC, and the meteorological conditions in 2019 were more severe than those in 2014, which was not conducive to the spread of pollutants.The correlation analysis and SOC estimation of OC and EC indicated that the correlation R 2 of OC and EC in Baoding in 2014 and 2019 were 0.874 and 0.811, respectively, indicating that OC and EC in Baoding had relatively consistent sources. The average values of ρ (SOC) in 2014 and 2019 were 16.59 μg·m -3 and 11.31 μg·m -3 , respectively, and the contribution rates to OC were 27.23% and 30.87%, respectively. This showed that in 2019, compared with that in 2014, the primary pollution decreased, but the secondary pollution increased, and the atmospheric oxidation increased.The analysis of the pollution sources of carbonaceous aerosols revealed that in 2014 and 2019 before and after the implementation of clean heating, the carbonaceous aerosols in the atmosphere were mainly from biomass combustion, coal combustion, and vehicle exhaust emissions. However, the contribution from biomass burning and coal burning decreased in 2019 compared to that in 2014. The decrease in OC and EC concentrations was attributed to the control of coal-fired and biomass-fired sources by clean heating. At the same time, the implementation of clean heating measures reduced the contribution of primary emissions to carbonaceous aerosols in PM 2.5 in Baoding City.

Objective: To observe the present situation, efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma (MPM). Methods: The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated. According to the application of immune checkpoint inhibitors (ICIs), these patients, whose median clinical follow-up amounting to 18.97 months, were divided into immunotherapy group (19 cases) and control group (20 cases). Kaplan-Meier method and Log-rank test were used for the survival analysis. Results: The objective response rate (ORR) and the disease control rate (DCR) in the immunotherapy group is 21.05% and 79.0% respectively, compared with 10.0% and 55.0% in the control group; and the difference was not statistically significant ( P >0.05). The median overall survival (OS) in the immunotherapy group was significantly longer than that in the control group (14.53 months vs 7.07 months, P =0.015), but there was no significant difference in the median progression free survival (PFS) between two groups (4.80 months vs 2.03 months, P =0.062). Single factor survival analysis showed that the nature of pleural effusion, pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM ( P <0.05). The incidence of adverse reactions in immunotherapy group was 89.5% (17 out of 19 cases), and the most common adverse event was hematological toxicity (9 cases), followed by nausea and vomiting (7 cases), fatigue (6 cases) and skin damage (6 cases). Five patients had immune checkpoint inhibitors (ICIs) related adverse reactions with grade 1-2. Conclusions: Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world, and the median treatment line is 2-line. Either combined with chemotherapy or anti-angiogenesis therapy, ICI inhibitors have significant efficacy, controllable adverse events and good clinical value.

A new species of Pseudopyrochroa Pic, 1906, P. reni Pan & Young, n. sp. , is described from the western region of Mt. Qinling, China. Larvae, pupae, and adults were associated using molecular phylogenetic analyses based on mtDNA COI barcode sequences. All three stages are described and illustrated. Additionally, preliminary phylogenetic relationships among five genera and 14 species of Pyrochroidae, including Pseudopyrochroa , are hypothesized based on COI sequence data. The fauna of Pyrochroidae from the Mt. Qinling biodiversity conservation area is discussed.

In order to achieve the overall victory over 2019 novel coronavirus disease epidemic, especially to prevent the disease recurrence from rebounding during the resumption of labor, the government has not loosened any control of personnel mobility, which has obviously affected the normal examination and treatment of lung cancer patients under the influence of this epidemic. During the epidemic period, cancer patients with low immunity levels face the double ordeals of disease and epidemic situation. Compared with the general population, they are more likely to be infected with the new coronavirus. Among the infected cancer patients, lung cancer is the most common type. It is necessary to provide more appropriate individualized treatment recommendations for patients with lung cancer based on the epidemic situation of the patient's location and in combination with the patient's own condition. Through active prevention of infection, timely conversion of treatment strategies, online and offline joint control, and positive psychological counseling, we do our best to help patients with lung cancer to survive this difficult period.

We report on successive haze weather that occurred in Shijiazhuang City, China, from December 30, 2018 to January 15, 2019. There were 12 days of heavy atmospheric pollution during this period, which primarily involved aerosol fine particulate matter (PM 2.5 ). This study analyzes the causes of the pollution using component analysis and by assessing pollution evolution, spatial and temporal distributions of PM 2.5 , pollution sources, and meteorological factors. The results showed that PM 2.5 was mainly composed of secondary inorganic ions (65.4%) that were mainly sourced from coal combustion (24.4%) and industrial sources (23.7%). The contributions of sulfate and secondary inorganic sources increased significantly with increasing pollution. Pollution was affected by unfavorable meteorological conditions (e.g., a low air mass) and by the particular local terrain, static stability, high humidity, and near-ground reverse temperatures from the south-southeast and west-southwest directions. Contaminants from primary sources including coal combustion, industry, and motor vehicle exhausts accumulated quickly in front of the Taihang Mountains. Secondary transformation of gaseous pollutants and increasing moisture absorption of particulate matter increased PM 2.5 concentrations. Sulfate explosion also increased pollution. We recommend that as part of emergency responses to heavy pollution events, emissions reduction measures should be implemented to strengthen the control of SO 2 , NO x , and NH 3 emission sources of secondary inorganic precursors, especially SO 2 emission sources (i.e., coal etc.). We further propose a strengthen of the management of atmospheric emission sources in Xinle, Wuji, Shenze, Jinzhou, and Xingtang counties in the northeast of the city to reduce the impact of local transmission.

This study assesses the chemical characteristics of As in aerosol PM 2.5 samples that were collected from July 2011 to May 2012 in Beijing, China. Total As, As(Ⅲ), and As(Ⅴ) were analyzed by inductively coupled plasma mass spectrometry (ICP-MS), high performance liquid chromatography (HPLC), and hydride generation atomic fluorescence (HG-AFS), respectively. The average concentrations of total As, As(Ⅲ) and As(Ⅴ) over the entire sampling period were (21.82±17.01), (3.15±1.94), and (10.78±5.39) ng·m -3 , respectively. The average concentrations of total As, As(Ⅲ) and As(Ⅴ) were (16.62±5.80), (18.34±9.00), (21.49±10.22), and (29.52±27.97) ng·m -3 during the spring, (5.42±2.5), (1.61±0.51), (2.88±1.12), and (3.27±1.23) ng·m -3 during the summer, and (7.55±1.47), (13.57±13.34), (12.75±6.54), and (8.68±3.57) ng·m -3 during the winter, respectively. The average concentrations of As(Ⅲ) in different seasons were higher than As(Ⅴ) concentrations. Seasonal characteristics may be caused by seasonal differences in diffusion conditions, emission sources, and atmospheric oxidation. The ratios of average concentrations of As(Ⅲ)/As(Ⅴ) were 0.67 in spring, 0.13 in summer, 0.27 in autumn, and 0.44 in winter. Ratios of As(Ⅲ)/As(Ⅴ) were negatively correlated with relative humidity, which indicates that high humidity conditions may not have been favorable for the transformation of As(Ⅲ) into As(Ⅴ). As(Ⅲ)/As(Ⅴ) and As(Ⅲ) both showed positive correlations with Ca 2+ , thereby indicating that soil dust may have been an important source of As(Ⅲ).

Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) are the two most frequent and well-known oncogene of lung adenocarcinoma. The purpose of this study is to compare the characteristics measured with dual-energy spectral computed tomography (DESCT) in lung adenocarcinoma patients who have KRAS and EGFR gene mutations., Methods: Patients with surgically resected lung adenocarcinoma (n = 72) were enrolled, including 12 patients with KRAS mutations and 60 patients with EGFR mutations. DESCT quantitative parameters, including the CT number at 70 keV, the slopes of the spectral attenuation curves (slope λ HU), normalized iodine concentration (NIC), normalized water concentration (NWC), and effective atomic number (effective Z), were analyzed. A multiple logistic regression model was applied to discriminate clinical and DESCT characteristics between the types of mutations., Results: The KRAS mutation was more common in people who smoked than the EGFR mutation. Nodule type differed significantly between the KRAS and EGFR groups (P = 0.035), and all KRAS mutation adenocarcinomas were solid nodules. Most DESCT quantitative parameters differed significantly between solid nodules and subsolid nodules. CT number at 70 keV, slope λ HU, NIC, and effective Z differed significantly between the KRAS and EGFR groups (P = 0.006, 0.017, 0.013 and 0.010) with solid lung adenocarcinoma. Multivariate logistic analysis of DESCT and clinical features indicated that besides smoking history, the CT value at 70 keV (OR = 0.938, P = 0.009) was significant independent factor that could be used to differentiate KRAS and EGFR mutations in solid lung adenocarcinoma., Conclusions: DESCT would be a potential tool to differentiate lung adenocarcinoma patients with a KRAS mutation from those with an EGFR mutation.

We present an experimental realization of a compact and reliable way to build a nondegenerate polarization-entangled photon-pair source based on a dual-periodically-poled $ {\rm Ti}:{{\rm LiNbO}&#95;3} $Ti:LiNbO 3 waveguide, which is in the telecommunication window and compatible with the fiber quantum networks. The dual-periodic structure allows two inherently concurrent quasiphase-matching spontaneous parametric down-conversion processes pumped by a single laser beam, hence enabling our source to be compact and stable. We show that our source has a high brightness of $ B = 1.22{\rm } \times {\rm }{10^7}\;{\rm pairs}/(\rm s \times mW \times nm) $B=1.22×10 7 pairs/(s×mW×nm). With quantum state tomography, we estimate an entanglement fidelity of $ 0.945 \pm 0.003 $0.945±0.003. A violation of Clauser-Horne-Shimony-Holt inequality with $ S = 2.75 \pm 0.03 $S=2.75±0.03 is also demonstrated.

Samples of particulate matter from coal-fired boilers of different tons were collected in Lanzhou city, and the water-soluble inorganic ions, carbonaceous species, water-soluble organic compounds (WSOC) and polycyclic aromatic hydrocarbons (PAHs) were analyzed. The results showed that SO 4 2- , Cl - , and Ca 2+ were the most important water-soluble ions in the coal-fired boiler samples, accounting for 35.13%, 23.16%, and 22.20% of the total mass of water-soluble ions, respectively. The pyrolysis composition spectra of the carbonaceous species were similar among the coal-fired boilers, and organic carbon fraction (OC1, OC2, OC3, and OC4),and elemental carbon fraction (EC1, EC2, and EC3) accounted for 1.04%, 8.26%, 20.09%, 6.78%, 51.08%, 7.09%, and 5.66% of the total carbon (TC), respectively. EC1 had the highest content and was the most important carbonaceous species. The average ratios of WSOC/TC and WSOC/OC were 0.09±0.07 and 0.23±0.12, respectively, and the difference among the boilers of different tons was large. Phenanthrene (Phe), pyrene (Pyr), and benzene(k)anthracene (BkF) were the three main components of the PAHs, accounting for 16.69%, 11.93%, and 10.66% of the total PAHs, respectively. The particulate water-soluble ions, organic/elemental carbon aerosol (OCEC) and WSOC emitted from different tons coal-fired boilers were not significantly linearly related to the tonnage of the steam boiler, and low molecular weight PAHs decreased with the increase of tonnage of the steam boiler.

Background This phase I trial was primarily conducted to determine the maximum tolerated dose (MTD) of apatinib combined with docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR who have failed to first-line platinum-based chemotherapy, and to evaluate the safety and tolerability of apatinib plus docetaxel. Methods This was a single-center, open-label, dose-escalating phase I trial. The study used a standard 3 + 3 dose escalation design with the primary aim of determining the MTD. Twelve patients with advanced lung adenocarcinoma were enrolled, the primary endpoint was safety. Two doses of apatinib, 250 mg/day (level 1) and 500 mg/day (level 2), were evaluated in combination with 60 mg/m 2 doxetacel every 3 weeks. Six patients have been treated at levels 1 and 2, respectively. Optimal dose of apatinib was determined by dose-limiting toxicity (DLT). Results Six patients have been treated at levels 1 and 2. At level 1, one of six patients experienced grade 3 acneiform rash as DLTs. At level 2, two patients experienced grade 3 hypertension and one experienced grade 3 nasal bleeding. MTD and recommended dose for phase II study was 250 mg/day. Most frequent adverse events of any grade were bilirubin elevation, hypertension, alanine aminotransferase elevation, transglutaminase elevation, hand foot syndrome and fatigue. The median progression-free survival was 2.76 month. Moreover, three patients had developed progressive disease and the mean duration of response was 2.79 months. Conclusion Apatinib plus docetaxel was well tolerated and showed promising efficacy in advanced lung adenocarcinoma. This combination therapy may represent a potent therapeutic option for advanced lung adenocarcinoma patients with wild-type EGFR.

Several animal models of migraine have been established, and those based on trigeminovascular system activation are widely accepted. However, most of these models have been established on lower animals, such as rodents, and involve only a single administration of a noxious stimulus. In this study, an inflammatory soup (10 μL), consisting of prostaglandin E2 (0.2 mM), serotonin (2 mM), bradykinin (2 mM) and histamine (2 mM), was injected into the dura mater of conscious rhesus monkeys through an indwelling catheter. The infusion started on day 8 and was repeated every 3 days, for a total of six administrations, to induce neurogenic inflammation. We performed behavioral assessments and measured the expression of the oncogene c-fos, neuronal nitric oxide synthase (nNOS) and calcitonin gene related peptide (CGRP) in the trigeminal system and in multiple brain regions involved in pain processing by immunohistochemical staining. Compared with monkeys in the control group, three of the four animals in the inflammatory soup group displayed decreased motor behaviors, and two showed increased ipsilateral nose and mouth secretions during the stimulus period. Higher expression levels of c-fos, nNOS and CGRP were found in various brain areas of experimental animals compared with controls, including the trigeminal nucleus caudalis, thalamus, hypothalamus, midbrain, pons and other areas involved in pain perception. These results suggest that repeated inflammatory soup stimulation of the dura activates the trigeminovascular system and produces migraine-like pathological changes and abnormal behaviors in conscious rhesus monkeys., Competing Interests: None

In this work, new lignin-based flame retardant LHDs were successfully synthesized through the reaction between lignin, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and hexamethylene diisocyanate (HDI). The chemical structure of LHD was characterized by FTIR, 1 H NMR, 31 P NMR. The thermal stability of LHD was studied by TGA. The results showed that the residual carbon content of L15HD (15% of lignin in LHD) at 600 °C reached 16.55%, indicating that this prepared flame retardant can be a type of good char forming agent. LHDs were then applied to prepare flame-retardant lignin-based polyurethane (FLPU). Lignin-based polyurethane (LPU) was synthesized by the reaction between lignin, polyethylene glycol 200 (PEG 200) and hexamethylene diisocyanate (HDI). The limiting oxygen index (LOI) value of the FLPU reached 30.2% when the addition content of L15HD (15% lignin in LHD) in L 20 PU (20% lignin in LPU) was 25%, exhibiting excellent flame-retardant properties. Scanning electron microscopy (SEM) analysis of the FLPU char residual showed that there was a continuous dense outer carbon layer on the residue surface, and the inner carbon layer had many expansion bubbles, indicating the LHDs have an excellent flame retardant effect for PU. In addition, FLPU presented better hardness and adhesion than PU. The hardness of F L15-25 L 20 PU (lignin content in LPU was 20%, and added content of L15HD in LPU was 25%) reached 4H, and its adhesion was 0. These excellent properties illustrated that the LHDs are ideal flame retardants and reinforcing agents for LPU because of the co-curing and strong interface between LHD and LPU., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In order to investigate the chemical characteristics and sources of atmospheric heavy metals, PM 2.5 samples were collected every three days during the summer of 2011 and summer of 2012. The samples were analyzed for Li, V, Cr, Mn, Co, Cu, Zn, As, Se, Ti, Ga, Ni, Sr, Cd, In, Ba, Tl, Pb, Bi, and U by ICP-MS, with an emphasis on seven major heavy metal elements (Zn, Pb, Mn, Cu, As, V, and Cr). The concentrations of Zn, Pb, Mn, Cu, As, V, and Cr were (331.30±254.52), (212.64±182.06), (85.96±47.00), (45.19±27.74), (17.13±19.02), (4.92±3.38), and (9.04±7.84) ng·m -3 in PM 2.5 in Beijing during the summer of 2011 and the summer of 2012. In the autumn and winter seasons, PM 2.5 /heavy metal pollution is more severe than in spring and summer, which may be related to the increase in coal combustion used for heating in autumn and winter in Beijing. Haze pollution enhances the concentrations of seven heavy metals in PM 2.5 in Beijing and the enhancement shows seasonal variations. The source analysis suggested that dust (including building dust and road dust) and coal combustion might be two most important sources of heavy metals in Beijing, and transport and other industrial sources cannot be ignored.

Simultaneous collections of non-methane hydrocarbons (NMHCs) were carried out at 15 sampling sites including urban, suburb and potential pollution areas in Cangzhou City in spring 2015. The results showed that NMHCs were generally higher in urban areas than those in suburb and rural areas; the highest concentration of NMHCs was observed at Cangzhou High-tech zone (urban area); the concentrations of NMHCs were significantly lower at rural sites than in most urban sites except Hejian site; vehicular emissions were the main sources of NMHCs in Cangzhou; Cangzhou chemical fertilizer plant and Cangzhou oil refinery had no significant influence on urban NMHCs during their shutdown period; Dagang Oilfield, with better oil and gas recovery systems, did not have a significant impact on urban NMHCs. In general, alkanes, alkenes and aromatics accounted for 65%, 16% and 19% of NMHCs in Cangzhou City, respectively; xylene (19%), ethylene (14%), toluene(11%), propylene (5%), isopentane (5%) and isopentene (5%) were the most dominant contributors to ozone formation potential; aerosol formation potential was mainly derived from toluene (28%), pinene (28%), xylene(16%), ethylbenzene (9%) and benzene (9%).

Our ability to predict how temperature modifies phenology at the community scale is limited by our lack of understanding of responses by functional groups of flowering plants. These responses differ among species with different life histories. We performed a reciprocal transplant experiment along four elevation gradients (e.g., 3,200, 3,400, 3,600 and 3,800 m) to investigate the effects of warming (transferred downward) and cooling (transferred upward) on plant flowering functional groups (FFGs) and community phenological sequences (i.e., seven phenological events). Warming significantly decreased early-spring-flowering (ESF) plant coverage and increased mid-summer-flowering plant (MSF) coverage, while cooling had the opposite effect. All community phenological events were advanced by warming and delayed by cooling except for the date of complete leaf-coloring, which showed the opposite response. Warming and cooling could cause greater advance or delay in early-season phenological events of the community through increased coverage of MSF species, and warming could delay late-season phenological events of the community by increased coverage of ESF species. These results suggested that coverage change of FFGs in the community induced by temperature change could mediate the responses of the community phenological events to temperature change in the future. The response of phenological events to temperature change at the species level may not be sufficient to predict phenological responses at the community-level due to phenological compensation between species in the community., (© 2016 by the Ecological Society of America.)

Elucidating arbuscular mycorrhizal (AM) fungal responses to elevation changes is critical to improve understanding of microbial function in ecosystems under global asymmetrical climate change scenarios. Here we examined AM fungal community in a two-year reciprocal translocation of vegetation-intact soil blocks along an altitudinal gradient (3,200 m to 3,800 m) in an alpine meadow on the Qinghai-Tibet Plateau. AM fungal spore density was significantly higher at lower elevation than at higher elevation regardless of translocation, except that this parameter was significantly increased by upward translocation from original 3,200 m to 3,400 m and 3,600 m. Seventy-three operational taxonomic units (OTUs) of AM fungi were recovered using 454-pyrosequencing of 18S rDNA sequences at a 97% sequence similarity. Original elevation, downward translocation and upward translocation did not significantly affect AM fungal OTU richness. However, with increasing altitude the OTU richness of Acaulosporaceae and Ambisporaceae increased, but the OTU richness of Gigasporaceae and Glomeraceae decreased generally. The AM fungal community composition was significantly structured by original elevation but not by downward translocation and upward translocation. Our findings highlight that compared with the short-term reciprocal translocation, original elevation is a stronger determinant in shaping AM fungal community in the Qinghai-Tibet alpine meadow.

Thirty non-methane hydrocarbons(NMHCs) samples were collected and analyzed in Foshan City during winter 2014 and summer 2015. The concentrations of NMHCs during the sampling period were 122.30 μg·m -3 and 56.22 μg·m -3 in winter and summer, respectively. The five highest concentration species of NMHCs in winter and summer were in the following order: toluene (25.12 μg·m -3 ), m/p -xylene (13.76 μg·m -3 ), propane (9.17 μg·m -3 ), ethylbenzene (7.25 μg·m -3 ), ethylene (6.77 μg·m -3 ) and toluene (6.18 μg·m -3 ), m/p -xylene (5.21 μg·m -3 ), o -xylene (4.15 μg·m -3 ), β -pinene(3.75 μg·m -3 ), propane (3.29 μg·m -3 ). Compared to 2008, the concentrations of NMHCs have dropped significantly. The proportions of aromatics, alkanes, alkenes and alkynes in NMHCs were 51.20%, 34.70%, 10.04%, 4.05% and 43.93%, 33.99%, 19.20%, 2.88% during winter and summer, respectively. The ratios of NMHCs/NO x were 0.90 and 1.88, indicating that the peak ozone concentrations in Foshan City were controlled by NMHCs during the sampling period, and the emissions of NMHCs should be further strengthened. The propylene equivalent concentration and ozone formation potential were 45.09 μg·m -3 and 40.64 μg·m -3 , 392.77 μg·m -3 and 207.77 μg·m -3 in winter and summer. The m/p -xylene; toluene and m/p -xylene; isoprene had a very important influence on ozone formation potential. The ratios of Benzene/Toluene were 0.15 and 0.20 indicated that industrial process was the main source of NMHCs in Foshan City. Relative to 2008, isopentane didn't belong to the highest concentration of five pollutants for Foshan's NMHCs in this research, indicating the measures to prevent volatile gasoline impact on the environmental quality have achieved remarkable results.

The timing of the fruit-set stage (i.e., start and end of fruit set) is crucial in a plant's life cycle, but its response to temperature change is still unclear. We investigated the timing of seven phenological events, including fruit-set dates during 3 yr for six alpine plants transplanted to warmer (approximately +3.5°C in soils) and cooler (approximately -3.5°C in soils) locations along an altitudinal gradient in the Tibetan area. We found that fruit-set dates remained relatively stable under both warming and cooling during the 3-yr transplant experiment. Three earlier phenological events (emergence of first leaf, first bud set, and first flowering) and two later phenological events (first leaf coloring and complete leaf coloring) were earlier by 4.8-8.2 d/°C and later by 3.2-7.1 d/°C in response to warming. Conversely, cooling delayed the three earlier events by 3.8-6.9 d/°C and advanced the two later events by 3.2-8.1 d/°C for all plant species. The timing of the first and/or last fruit-set dates, however, did not change significantly compared to earlier and later phenological events. Statistical analyses also showed that the dates of fruit set were not significantly correlated or had lower correlations with changes of soil temperature relative to the earlier and later phenological events. Alpine plants may thus acclimate to changes in temperature for their fruiting function by maintaining relatively stable timings of fruit set compared with other phenological events to maximize the success of seed maturation and dispersal in response to short-term warming or cooling., (© 2016 by the Ecological Society of America.)

Polycyclic aromatic hydrocarbons (PAHs) are a group of important toxic compounds. In order to detect the pollutional characteristics of atmospheric PAHs in Fine Particulate Matter (PM 2.5 ), a total of 60 PM 2.5 samples were collected in Lanzhou City during the winter of 2012 and summer of 2013. The GC/MS measurement results of the samples demonstrated the averagely total mass concentrations of the most significant 16 homologues of PAHs were (191.79±88.29) ng·m -3 and (8.94±4.34) ng·m -3 in winter and summer respectively, indicating a higher pollution level in winter. In winter, the snowfall was the most important meteorological factor for the decrease of PAHs mass concentration in PM 2.5 . The percentages of PAHs with 4 rings were the highest in both winter (51.40%) and summer (49.94%) in Lanzhou. The percentage of PAHs with 5-6 rings in summer (41.04%) was higher than that in winter (24.94%). However, the percentage of PAHs with 2-3 rings in summer (9.03%) was lower than that in winter (23.67%). Based on the analysis of characteristic ratios, we concluded that the PAHs in atmospheric PM 2.5 in Lanzhou were mainly sourced from coal and vehicle emissions in winter, especially the diesel vehicles. The absolute contributions of all possible PAHs pollution sources were insignificant in summer, with relatively higher contribution from gasoline vehicles.

In order to investigate the influence of the emission reduction measure during the Beijing APEC on the concentrations and pollution characteristics of humic-like substances (HULIS) in atmospheric fine particles, PM₂.₅ samples were collected and analyzed for OCEC, WSOC, HULIS and water-soluble ions. The concentration of HULIS in PM₂.₅ ranged 1 µg · m⁻³-15 µg · m⁻³. HULIS concentrations were 7.99 µg · m⁻³, 5.83 µg · m⁻³ and 7.06 µg · m⁻³ before, during and after APEC, which indicated emission reduction measure had important effect on the reduction of HULlS. The decrease of HULIS during the APEC was significantly faster than those of EC and WSOC, while the increase of HULIS turned out to be much slower than OC, EC, WSOC and PM₂.₅ after the meeting. The proportions of HULIS to PM₂.₅ were 13.60%, 13.59%, 14.02% and 12.22% at four different stages, i. e., whole sampling period, before, during and after the APEC, while HULIS-C/OC and HULIS-C/WSOC were 28.95%, 35.51%, 28.37%, 19.93%; and 52.75%, 59.58%, 51.54%, 45.39%, respectively. HULlS was significantly positively correlated with humidity, while significantly negatively correlated with wind speed. Biomass burning and secondary transformation of VOCs might be two important sources of HULlS in Beijing.

Background: Epidermal growth factor receptor (EGFR) mutations, including a known exon 19 deletion (19 del) and exon 21 L858R point mutation (L858R mutation), are strong predictors of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment in lung adenocarcinoma. However, whether patients carrying EGFR 19 del and L858R mutations exhibit different responsiveness to EGFR-TKIs and what are the potential mechanism for this difference remain controversial. This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes., Methods: Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858R mutations, 532 received EGFR-TKI treatment and were included in this study. EGFR 19 del and L858R mutations were detected by using denaturing high-performance liquid chromatography (DHPLC). T790M mutation, which is a common resistant mutation on exon 20 of EGFR, was detected by amplification refractory mutation system (ARMS). Next-generation sequencing (NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858R mutations., Results: Of the 532 patients, 319 (60.0%) had EGFR 19 del, and 213 (40.0%) had L858R mutations. The patients with EGFR 19 del presented a significantly higher overall response rate (ORR) for EGFR-TKI treatment (55.2% vs. 43.7%, P = 0.017) and had a longer progression-free survival (PFS) after first-line EGFR-TKI treatment (14.4 vs. 11.4 months, P = 0.034) compared with those with L858R mutations. However, no statistically significant difference in overall survival (OS) was observed between the two groups of patients. T790M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment, and there was no significant difference in the co-existence of T790M mutation with EGFR 19 del and L858R mutations before EGFR-TKI treatment (5.6% vs. 8.8%, P = 0.554) or after treatment (24.4% vs. 35.4%, P = 0.176). In addition, 24 patients with EGFR 19 del and 19 with L858R mutations were analyzed by NGS, and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes., Conclusions: Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858R mutations. Whether the heterogeneity of tumors with EGFR 19 del and L858R mutations contribute to a therapeutic response difference needs further investigation.

Hepatitis B virus (HBV) prevalence has declined remarkably in children due to nationwide universal vaccination program for HBV in China. However, the persistence of immune response against HBV infection and the optimal time point when a booster vaccination should be performed remain to be elucidated. To assess the persistence and level of antibody against hepatitis B surface antigen (anti-HBs) in a representative population of age 15 and younger who received routine hepatitis B vaccination in Mianyang City, China. A cross-sectional study was conducted in 2011. One thousand five hundred twenty-six children of age 15 and younger who received three doses of 5 μg hepatitis B vaccine series during infancy but did not receive a booster vaccination later were enrolled. Of the 1,526 children, the mean age was 8.2 ± 4.1 and 739 children were male. The median anti-HBs level was 23.0 mIU/mL, and the total percentage of anti-HBs levels ≥10 mIU/mL was 60.9%. With an increase of age, median anti-HBs level, percentage of anti-HBs levels ≥10 mIU/mL, and percentage of anti-HBs levels ≥100 mIU/mL declined remarkably in the early period and reached the lowest level at the age of 3 and then remained relatively stable. The median anti-HBs level, the percentage of anti-HBs levels ≥10 mIU/mL, and the percentage of anti-HBs levels ≥100 mIU/mL in 1- and 2-year-old children were much higher than that in children aged 3-15 (p < 0.05, respectively). Immunity against HBV infection gradually decreased in early ages of children of 15 and younger who received three doses of 5 μg hepatitis B vaccine series during infancy in China. Three dosages of 10 μg hepatitis B vaccine for infants and repeated vaccination or additional booster vaccination for some children at or before age 3 should be provided to get much more powerful immunity to HBV.

Aim: To investigate the effect of hepatocyte nuclear factor 4α (HNF4α) on the differentiation and transformation of hepatic stellate cells (HSCs)., Methods: By constructing the recombinant adenovirus vector expressing HNF4α and HNF4α shRNA vector, and manipulating HNF4α expression in HSC-T6 cells, we explored the influence of HNF4α and its induction capacity in the differentiation of rat HSCs into hepatocytes., Results: With increased expression of HNF4α mediated by AdHNF4α, the relative expression of Nanog was downregulated in HSC-T6 cells (98.33 ± 12.33 vs 41.33 ± 5.67, P < 0.001). Consequently, the expression of G-P-6 and PEPCK was upregulated (G-P-6: 14.34 ± 3.33 vs 42.53 ± 5.87, P < 0.01; PEPCK: 10.10 ± 4.67 vs 56.56 ± 5.25, P < 0.001), the expression of AFP and ALB was positive, and the expression of Nanog, Type I collagen, α-SMA, and TIMP-1 was significantly decreased. HNF4α also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4α-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4α expression, EPCK, E-cadherin, AFP, and ALB were downregulated and α-SMA and vimentin were upregulated., Conclusion: HNF4α can induce a tendency of differentiation of HSCs into hepatocyte-like cells. These findings may provide an effective way for the treatment of liver diseases.

Rechallenge chemotherapy with pemetrexed was shown to be efficient in malignant pleural mesothelioma; however, its role in non-small-cell lung cancer (NSCLC) has not been investigated. In this study, we retrospectively enrolled 31 patients with non-squamous NSCLC who had achieved disease control with initial pemetrexed treatment, followed by rechallenge with pemetrexed-based chemotherapy (PBC) upon disease progression. After the rechallenge, 5 patients (16.1%) achieved partial remission (PR), 17 (54.8%) achieved stable disease (SD) and 9 (29.1%) experienced progressive disease. The treatment was generally well tolerated, with a low rate of toxicity. The median progression-free survival (PFS) was 3.8 months with the rechallenge. Patients with a PFS of ≥10 months with initial PBC exhibited longer PFS and overall survival (OS) with the rechallenge compared to those with a PFS of <10 months with initial PBC (PFS: 6.2±0.33 vs. 3.1±0.26 months, respectively; P=0.011; and OS, 19.8±3.2 vs. 9.2±1.1 months, respectively; P=0.005). The time from the termination of initial PBC to disease progression was also associated with survival after the rechallenge. However, the response to initial PBC (PR vs. SD) did not affect PFS after the rechallenge. No significant differences were observed in thymidylate synthase expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene fusion, or epithelial growth factor receptor mutation status between pemetrexed-sensitive and pemetrexed-resistant patients. Our results demonstrated that rechallenge with PBC was well tolerated and survival after the rechallenge was associated with survival during initial PBC. Therefore, patients with a PFS of ≥10 months or time-to-disease progression ≥3 months may be considered as candidates for pemetrexed rechallenge.

Background: Drug resistance significantly weakens the efficacy of cancer treatment, and the BIM (also known as the BCL2L11 gene) deletion polymorphism has been identified as a potential biomarker for drug resistance. In this retrospective study, we included a total of 290 patients with advanced non-small cell lung cancer (NSCLC) who received treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy., Methods: The BIM deletion polymorphism of each patient was detected by polymerase chain reaction. EGFR mutations were detected by denaturing high-performance liquid chromatography methods and the amplification refractory mutation system., Results: The BIM deletion polymorphism was detected in 45/290 (15.5%) Chinese NSCLC patients. No associations were observed between the BIM deletion and clinic-pathologic characteristics of patients. The BIM deletion polymorphism was predictive of shorter progression-free survival in Chinese patients with EGFR-mutant adenocarcinoma and who were treated with EGFR-TKIs (7.30 vs. 9.53 months, P = 0.034). Additionally, we found that the BIM deletion polymorphism was an effective predictor of short progression-free survival in individuals with EGFR-mutant NSCLC and treated with chemotherapy containing pemetrexed (3.32 vs. 5.30, P = 0.012) or second-/beyond-line chemotherapy containing taxanes (1.53 vs. 2.61 months, P = 0.025). The BIM deletion was not correlated with overall survival., Conclusion: The BIM deletion polymorphism occurs in 15.5% of Chinese NSCLC patients, and is a biomarker for resistance to TKIs and chemotherapy. However, BIM deletion was not a decisive factor in overall survival.

Foshan is a ceramics manufacturing center in the world and the most polluted city in the Pearl River Delta (PRD) in southern China measured by the levels of atmospheric heavy metals. PM2.5 samples were collected in Foshan in winter 2008. Among the 22 elements and ions analyzed, 7 heavy metals (Zn, V, Mn, Cu, As, Cd and Pb) were studied in depth for their levels, spatiotemporal variations and sources. The ambient concentrations of the heavy metals were much higher than the reported average concentrations in China. The levels of Pb (675.7 ± 378.5 ng/m(3)), As (76.6 ± 49.1 ng/m(3)) and Cd (42.6 ± 45.2 ng/m(3)) exceeded the reference values of NAAQS (GB3095-2012) and the health guidelines of the World Health Organization. Generally, the levels of atmospheric heavy metals showed spatial distribution as: downtown site (CC, Chancheng District)>urban sites (NH and SD, Nanhai and Shunde Districts)>rural site (SS, Shanshui District). Two sources of heavy metals, the ceramic and aluminum industries, were identified during the sampling period. The large number of ceramic manufactures was responsible for the high levels of atmospheric Zn, Pb and As in Chancheng District. Transport from an aluminum industry park under light north-west winds contributed high levels of Cd to the SS site (Shanshui District). The average concentration of Cd under north-west wind was 220 ng/m(3), 20.5 times higher than those under other wind directions. The high daily maximum enrichment factors (EFs) of Cd, Pb, Zn, As and Cu at all four sites indicated extremely high contamination by local emissions. Back trajectory analysis showed that the heavy metals were also closely associated with the pathway of air mass. A positive matrix factorization (PMF) method was applied to determine the source apportionment of these heavy metals. Five factors (industry including the ceramic industry and coal combustion, vehicle emissions, dust, transportation and sea salt) were identified and industry was the most important source of atmospheric heavy metals. The present paper suggests a control policy on the four heavy metals Cd, Pb, Zn, and Cu, and suggests the inclusion of As in the ceramic industry emission standard in the future., (Copyright © 2014 Elsevier B.V. All rights reserved.)

During April, July, October 2009 and January 2010, daily (24-h average) PM2.5 samples were collected at urban sites in Beijing and 29 metal elements were analyzed by the ICP-MS. The characteristics of 7 carcinogenic heavy metal mass concentrations, enrichment, and possible sources were discussed. The annual average concentrations of As, Cd, Co, Cr, Ni, Pb and Se were (11.6 +/- 14.0), (2.6 +/- 2.4), (1.0 +/- 0.7), (11.3 +/- 9.4), (4.0 +/- 2.4), (142.5 +/- 98.9) and (3.3 +/- 2.2) ng m(-3), respectively. Only annual average concentration of As exceeded WHO standard by a factor of 0.8. Higher enrichment factors of As, Cd, Pb and Se were found and their enrichment factors exceeded 500. Their enrichment factors in summer were much higher than those in other seasons. The local coal combustion and vehicle exhaust should be the dominant sources for the above four carcinogenic heavy metals in spring, autumn and winter, while regional transportation contributed more in summer.

NMHCs and NOx samples were simultaneously collected and analyzed in six urban and suburban representative sampling sites (Sihuan, Tian'anmen, Pinguoyuan, Fatou, Beijing Airport and Miyun) during a typical haze period in winter 2005, Beijing. The concentrations of NMHCs during the sampling period in descending order were: Sihuan (1101.29 microg x m(-3)) > Fatou (692.40 microg x m(-3)) >Tian'anmen (653.28 microg x m(-3)) >Pinguoyuan (370.27 microg x m(-3)) > Beijing Airport (350.36 microg x m(-3)) > Miyun (199.97 microg x m(-3)). Atmospheric benzene pollution in Beijing was rather serious. The ratio of NMHCs/NOx ranged from 2.1 to 6.3, indicating that the peak ozone concentrations in urban Beijing were controlled by VOCs during the sampling period. Analysis of propylene equivalent concentration and ozone formation potential showed that the NMHCs reactivity descended in the order of Sihuan > Fatou > Tian'anmen > Pinguoyuan > Beijing Airport > Miyun. B/T values (0.52 to 0.76) indicated that besides motor vehicle emission, coal combustion and other emission sources were also the sources of NHMCs in Beijing in winter. The spatial variations of isoprene in Beijing indicated that the contribution of anthropogenic sources to isoprene increased and the emissions by biogenic sources decreased in winter. The spatial variations of propane and butane indicated that LPG emissions existed in the urban region of Beijing.

Total suspended particles (TSP), collected during a typical haze period in Guangzhou, were analyzed for the fatty acids (C12-C30) and low molecular weight dicarboxylic acids (C3-C9) using gas chromatography/mass spectrometry (GC/MS). The results showed that the concentration of total fatty and carboxylic acids was pretty high during the haze episode. The ratios of fatty acids and carboxylic acids in haze to those in normal days were 1.9 and 2.5, respectively. During the episode of the increasing pollution, the fatty acids and carboxylic acids at night (653 ng x m(-3)) was higher than that (487 ng x m(-3)) in days. After that, the level of fatty acids and carboxylic acids in days (412 ng x m(-3)) was higher than that (336 ng x m(-3)) at night. In general, the time-series of fatty acids and carboxylic acids was similar to that of the air particle and carbonaceous species, however, the trend of the ratio of fatty acids and carboxylic acids to organic carbon was opposite to that of air particle and carbonaceous species. This ratio decreased with the increase of the concentration of air particle and after the night of 27th, the ratio increased with the decrease in the concentration of air particle. The results showed that haze pollution had a significant inhibitory effect on the enrichment of fatty and carboxylic acids. Based on the ratio of malonate to succinate (C3/C4), it could be found that primary sources contribute more to the atmospheric fatty and carboxylic acids during the autumn haze pollution periods in Guangzhou.

Objective: To compare the pharmacokinetics of gentiopicroside and Gentianae Radix extract in rats and assess the effect of other components in Gentianae Radix on the pharmacokinetics of gentiopicroside., Methods: The rats were oral administrated with gentiopicroside and Gentianae Radix extract, the content of geritiopicroside was chosen as index and determined by HPLC. The pharmacokinetic parameters were calculated with DAS 2.1.1 program., Results: The concentration-time curve of gentiopicroside and Gentianae Radix extract was described by two compartment model. The main pharmacokinetic parameters of gentiopicroside and Gentianae Radix extract were: C(max) (16.53 +/- 0.37) g/mL and (16.61 +/- 0.49) g/mL, T(max) 0.25 h and 1.5 h, t1/2(alpha) (0.20 +/- 0.04) h and (0.69 +/- 0. 14) h, t /2 (beta) (0.64 +/- 0.08) hand (0.80 +/- 0.11) h, AUC(0-infinity) (18.20 +/- 1.97) g x h/mL and (39.20 +/- 1.18) g x h/mL, CL( 2.75 +/- 0.32) L/(h x kg) and (1.22 +/- 0.04) L (h x kg), respectively., Conclusion: There are significantly differences in pharmacokinetic parameters between gentiopicroside and Gentianae Radix extract in rats.

Aim: To investigate the significance of Twist2 for colorectal cancer (CRC)., Methods: In this study, 93 CRC patients were included who received curative surgery in Eastern Hepatobiliary Surgery Hospital from January 1999 to December 2010. Records of patients' clinicopathological characteristics and follow up data were reviewed. Formalin-fixed, paraffin-embedded tissue blocks were used to observe the protein expression of Twist2 and E-cadherin by immunohistochemistry. Two independent pathologists who were blinded to the clinical information performed semiquantitative scoring of immunostaining. A total score of 3-6 (sum of extent + intensity) was considered as Twist2-positive expression. The expression of E-cadherin was divided into two levels (preserved and reduced). An exploratory statistical analysis was conducted to determine the association between Twist2 expression and clinicopathological parameters, as well as E-cadherin expression. Furthermore, the variables associated with prognosis were analyzed by Cox's proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of Twist2., Results: Twist2-positive expression was observed in 66 (71.0%) samples and mainly located in the cytoplasm. Forty-three (46.2%) samples showed reduced expression of E-cadherin. There were no significant correlations between Twist2 expression and any of the clinicopathological parameters. However, Twist2-positive expression was significantly associated with reduced expression of E-cadherin (P = 0.040). Multivariate analysis revealed that bad M-stage [hazard ratio (HR) = 7.694, 95%CI: 2.927-20.224, P < 0.001] and Twist2-positive (HR = 5.744, 95%CI: 1.347-24.298, P = 0.018) were the independent risk factors for poor overall survival (OS), while Twist2-positive (HR = 3.264, 95%CI: 1.455-7.375, P = 0.004), bad N-stage (HR = 2.149, 95%CI: 1.226-3.767, P = 0.008) and bad M-stage (HR = 10.907, 95%CI: 4.937-24.096, P < 0.001) were independently associated with poor disease-free survival (DFS). Survival curves showed a definite trend for Twist2-negative patients to have longer OS and DFS than Twist2-negative patients, not only overall, but also for patients in different stages, especially for DFS of patients in stage III (P = 0.033) and IV (P = 0.026)., Conclusion: Our data suggests, for the first time, that Twist2 is a valuable prognostic biomarker for CRC, particularly for patients in stage III and IV.

Objective: To identify potential prognosis related clinical and molecular factors in malignant pleural mesothelioma (MPM)., Methods: Seventy-nine patients with MPM treated in Beijing Cancer Hospital from June 1996 to May 2012 were enrolled in this study. Clinical and pathological data were collected, including age, gender, smoking status, treatment, response, and molecular biomarkers such as thymidylate synthetase (TS) expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangement. The primary endpoint was overall survival (OS). SPSS 16.0 statistical analysis software was used for univariate analysis. The expression of TS was detected by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) was performed to detect EML4-ALK gene rearrangement. Efficacy of the chemotherapy regimen including pemetrexed was analyzed with these molecular biomarkers., Results: The median survival time (MST) of all patients was 15.5 months (95% CI: 10.6 - 20.4). Univariate survival analysis revealed that treatment factors including receiving operation, systemic chemotherapy, pemetrexed-based chemotherapy and capability of receiving second (or above) line chemotherapy were significantly related with OS. The MST of patients receiving operation was 5.4 months (95% CI: 3.6 - 7.3), significantly shorter than the 17.7months (95% CI: 11.8 - 23.5) in those who didn't receive operation (P = 0.030). Patients receiving systemic chemotherapy had a longer MST of 18.0 months (95% CI: 12.3 - 23.8) as compared to the 7.9 months (95% CI: 1.1 - 14.7) in those who didn't (P = 0.001). The MST of pemetrexed-based chemotherapy was 21.9 months (95% CI: 14.1-29.7) compared with 8.8 months (95% CI: 4.2 - 13.4) of regimens without pemetrexed (P = 0.000). For patients capable of receiving second (or above) line chemotherapy the MST was longer (21.0 months, 95% CI: 12.7 - 29.3) than those who could not (12.1 month, 95% CI: 6.4 - 17.8 month), P = 0.022. For the 42 patients treated with pemetrexed-based chemotherapy, the objective response rate (ORR) was 33.3% (14/42), the disease control rate (DCR) was 78.6% (33/42), the median progression-free survival (PFS) was 4.8 months (95% CI: 3.6 - 6.0) and MST was 21.9 months (95% CI: 14.1 - 29.7). Twenty-nine patients provided adequate specimens for detection of TS expression and 6 cases (20.7%) were positive. EML4-ALK gene rearrangement was studied in 32 patients and 6 (18.8%) were positive. TS expression was found to be inversely related to PFS of pemetrexed-based chemotherapy (P = 0.041). The MST was 19.6 months (95% CI: 6.0 - 7.9) in EML4-ALK-positive patients and 9.57 months (95% CI: 2.7 - 4.3) in negative ones (P = 0.159)., Conclusions: Systemic chemotherapy especially pemetrexed-based regimen was proved to be a superior option for MPM with a significantly prolonged OS. Correlation between TS expression or EML4-ALK rearrangement and outcome of pemetrexed-based chemotherapy for MPM may contribute to future individualized treatment, which needs further validation from large-scale prospective studies.

Aim:   There is no clear consensus on the optimal timing of surgical resection for synchronous colorectal liver metastases (SCLM). This study is a meta-analysis of the available evidence., Methods:   Systematic review and meta-analysis of trials comparing outcomes following simultaneous resection with staged resection for SCLM published from 1990 to 2010 in PubMed, Embase, Ovid and Medline. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (95% CI) were calculated using either the fixed effects or random effects model., Results:   Nineteen non-randomized controlled trials (NRCT) studies were included in this analysis. These studies included a total of 2724 patients: 1116 underwent simultaneous resection and 1608 underwent staged resection. Meta-analysis showed that shorter hospital stay (P < 0.001) and lower total complication rate (P < 0.001) were observed in patients undergoing simultaneous resection group. The overall survival rate in the simultaneous resection group did not statistically differ with that in the staged resection group at 1 year (P = 0.13), 3 years (P = 0.26), 5 years (P = 0.38), as well as the 1, 3 and 5 years disease-free survival rates (respectively, P = 0.55; P = 0.16; P = 0.12). No significant difference was noted between the two groups in terms of mortality (P = 0.16), intraoperative blood loss (P = 0.06) and recurrence (P = 0.47)., Conclusion:   Simultaneous resection is safe and efficient in the treatment of patients with SCLM while avoiding a second laparotomy. In selected patients, simultaneous resection might be considered as the preferred approach. However, the findings have to be carefully interpreted due to the lower level of evidence and the existence of heterogeneity., (© 2012 The Japan Society of Hepatology.)

Objective: To investigate the frequency of epidermal growth factor receptor (EGFR) mutations and their correlation with the efficacy of tyrosine kinase inhibitors (EGFR-TKI) in advanced squamous cell lung cancer., Methods: This retrospective study enrolled 79 patients with advanced squamous cell lung cancer who received EGFR-TKI at Department of Thoracic Medical Oncology in Peking University Cancer Hospital from June 2004 to June 2011. Among them, 67 patients had tissue and/or plasma EGFR exon 19 and 21 mutation detection in order to make an analysis on the relationship between EGFR mutation and the TKI's effect., Results: The disease control rate (DCR) was 56% in all the patients. The median progression free survival (mPFS) and median overall survival (mOS) was 3.7 months (95%CI: 2.0 - 5.0) and 11.5 months (95%CI: 6.6 - 14.2), respectively. Of the 67 patients who received EGFR mutation detection, there were 31 patients harboring EGFR-mutation, for whom the DCR was 71% (22/31), and mPFS and mOS was 6.3 months (95%CI: 2.2 - 10.0) and 13.5 months (95%CI: 7.3 - 18.6) respectively. 36 patients' EGFR status were wild type, for whom the DCR was 44% (16/36), mPFS and mOS was 2.2 months (95%CI: 1.1 - 4.0) and 6.4 months (95%CI: 4.0 - 12.0). There were 17 patients who received erlotinib and 7 patients who received gefitinib as second or more line treatment. mPFS and mOS were 7.9 months and 15.8 months in the erlotinib group, respectively; and the mPFS and mOS were both 6.3 months in gefitinib group; the difference between the 2 groups did not reach statistical significance. Cox-regression analysis showed that EGFR mutation was significantly correlated with PFS and OS (P < 0.05, respectively). EGFR mutation was significantly correlated with DCR by Chi-square test, P < 0.05., Conclusions: EGFR mutation was a predictor for advanced squamous cell lung cancer to EGFR-TKI. However, the effect was inferior in advanced squamous cell lung cancer as compared to lung adenocarcinoma. Erlotinib tended to be superior to gefitinib.

Objective: To evaluate the effect of pemetrexed plus platinum for chemotherapy-naive advanced non-small cell lung cancer (NSCLC), and to explore thymidylate synthetase (TS) expression as the predictive and prognostic factor for this treatment., Methods: This retrospective study enrolled 51 patients with chemotherapy-naive advanced NSCLC (non-squamous) treated at Department of Thoracic Medical Oncology in Beijing Cancer Hospital from Jan 2008 to Oct 2009. All patients received pemetrexed plus platinum as first-line treatment. TS expression was detected in 30 patients who had enough tissue samples by immunohistochemistry., Results: The objective response rate (ORR) was 37.3%. Median progression-free survival (PFS) was 5.3 months (95%CI: 3.9 - 6.7), and median overall survival (OS) was 19.0 months (95%CI: 11.6 - 26.4). Univariate analysis showed that gender, pathology, smoking status and response were significantly correlated with OS. Cox-regression analysis showed that pathology was an independent prognostic factor. Rate of Grade 3/4 adverse events was low. In 30 patients with enough tissue samples were available, TS expression positive rate was 33.3% (10/30). Chi-square test showed that TS expression was not associated with ORR. Multivariate analysis showed that pathology, response and TS expression (P = 0.003, 0.005 and 0.001, respectively) were the prognostic factors., Conclusion: The therapeutic effect and tolerance of pemetrexed plus platinum regiment were definite as first-line treatment for chemotherapy-naive advanced NSCLC, and TS expression was an independent prognostic factor.

Objective: To investigate the association between rs751141 gene polymorphisms in EPHX2 gene and essential hypertension in Kazak and Han in Xinjiang., Methods: A total of 267 essential hypertensive patients in Kazaks, 368 essential hypertensive patients in Hans, 284 normotensive controls in Kazaks and 348 normotensive controls in Hans were enrolled in this study. TaqMan assay was used to detect the rs751141 G/A gene polymorphisms of EPHX2 gene., Results: The rs751141 G/A genotype frequencies for GA + AA genotypes was 40.2 percent in essential hypertensive subjects and 52.0 percent in control subjects in Hans, respectively. The genotype frequencies were significant difference between the two groups in Hans in Xinjiang (P < 0.01). The rs751141G/A gene polymorphism had no significant difference between essential hypertensive patients and normotensive controls in Kazaks in Xinjiang (P > 0.05)., Conclusion: The essential hypertension in Kazaks in Xinjiang is not associated with rs751141G/A gene polymorphism of EPHX2 gene, but the essential hypertension in Hans in Xinjiang is associated with rs751141G/A allele gene polymorphism of EPHX2 gene. A type of rs751141 allele gene polymorphism may be the independent protective factor of essential hypertension in Hans in Xinjiang.

Background: The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis., Methods: We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes., Results: There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs. 31.9%). The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types (24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P = 0.047). Clinical stage (IV vs. IIIb), response to the first-line chemotherapy (partial vs. no) and EGFR genotype were independent prognostic factors., Conclusion: Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.

Background: Massive presacral venous plexus hemorrhage during radical resection of rectal carcinoma is rare, but when it occurs, bleeding can be uncontrollable, leading to death in some cases. Medical adhesive gauze sticking and packing and thumbtack compressive fixation are often used for hemostasis, but these methods are not effective in cases of uncontrollable massive hemorrhage. Therefore, identifying a practical, accurate, and reliable method of hemostasis in these cases is essential., Methods: Between January 2004 and December 2009, we treated 3 patients with massive presacral venous plexus hemorrhage during resection of rectal carcinoma by placing small, trimmed thin steel plates at the bleeding sites. The plates were fixed with a saddle-type application of thumbtacks., Results: Bleeding was successfully controlled in all 3 patients, and intestinal anastomosis was carried out after hemostasis. No complications were observed., Conclusions: Application of a small, thin steel plate to the bleeding site with thumbtack fixation is a simple and effective method of hemostasis in patients with massive presacral venous plexus hemorrhage during resection of rectal carcinoma.