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In the presence of a Cinchona alkaloid-based squaramide organocatalyst, the [3+2] cycloaddition of isatin-derived azomethine ylides with maleimides proceeded readily, thus delivering the desired pyrrolidine-fused spirooxindoles in 61-89% yields with >20:1 dr and 12 to >99 % ee. The absolute configuration of 5-chloro-1,5′-dimethyl-3′-phenyl-3′,3a′-dihydro-2′ H-spiro[indoline-3,1′-pyrrolo[3,4- c]pyrrole]-2,4′,6′(5′ H,6a′ H)-trione was unambiguously determined by means of X-ray single crystal structure analysis. The reaction mechanism was hypothesized to account for the enantioselective formation of 5-chloro-1,5′-dimethyl-3′-phenyl-3′,3a′-dihydro-2′ H-spiro[indoline-3,1′-pyrrolo[3,4- c]pyrrole]-2,4′,6′(5′ H,6a′ H)-trione. [ABSTRACT FROM AUTHOR]

Studies have shown that hepatitis B virus (HBV) infection may play an important role in the lymphomagenesis of lymphoma, but no studies regarding the relationship between HBV infection and extranodal natural killer/T cell lymphoma (ENKTL) have been reported previously. One hundred and seven patients diagnosed with ENKTL were retrospectively reviewed. The hepatitis B surface antigen (HBsAg)-positive rate was 13.1%, and no significant correlation existed between HBV infection and clinical characteristics (p > 0.05). No significant difference existed in complete remission rate between HBsAg-positive and -negative groups (42.9% vs. 44.1%, p = 1.000). In a multivariate Cox regression model that included international prognostic index (IPI) score, induction chemotherapy regimen and HBsAg status, all these variables were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) (p < 0.05). In conclusion, the HBsAg-positive rate in ENKTL was similar to that of the normal population in a high HBV endemic area, and HBsAg-positive status was an independent prognostic factor for OS and PFS. [ABSTRACT FROM AUTHOR]

Objective: To investigate the physical and mental development of children of assisted reproductive techniques(ART) at 1-3 years, in the limited samples and the limited age range. Methods: A total of 266 ART children, including 106 twins, at 1-3 years were follow-up visited from February 2008 to February 2011. The control group comprised 129 children, including 84 twins, who were naturally bred. The neonatal outcomes, physical and mental development were evaluated. Results: Parent age in the ART children group was elder than that in control group. There were no significant differences in BMI, MDI and PDI between two groups of ART children and control, and between two twins' groups. A multivariate regression analysis indicated that the conception mode did not affect MDI and PDI. Conclusions: There are no significantly differences in the physical and psychomotor development between ART children and normal conception children in this study. [ABSTRACT FROM AUTHOR]

Carbon dots capped with polyethyleneimine (CD-PEI) were synthesized and applied in selective separation and preconcentration of trace Cr(VI). Dispersed particle extraction (DPE) slurry sampling with flame atomic absorption spectrometry (FAAS) was used to selectively and sensitively determine Cr(VI) in water samples. The as-synthesized CD-PEI was confirmed by Fourier transform infrared spectroscopy, high-resolution transmission electron microscopy, elemental analysis, fluorescence and zeta potential measurement. The adsorption of Cr(VI) on CD-PEI was evaluated. Its isothermal adsorption was studied and fitted in the Langmuir model. Nearly 85% of Cr(VI) was adsorbed within 10 min showed that the CD-PEI exhibited fairly fast kinetics for the sorption of Cr(VI). Experimental conditions, including the content and size of CD-PEI, sample pH, adsorption time, sample volume, slurry volume and interfering ions, were further optimized to obtain efficient preconcentration and high-precision determination of Cr(VI). CD-PEI with small size turned to be a good candidate for the preparation of slurry. CD-PEI served not only as a promising adsorbent for separation and preconcentration of Cr, but also a signal-enhancing agent in FAAS. The method achieved an enhancement factor of 30 and a detection limit (S/N=3) of 0.21 µg L −1 Cr(VI) with a consumption of 14.0 mL sample and an adsorption time of 5 min, which provided two times of signal enhancement. The RSD for 11 replicate measurements of 5.0 µg L −1 Cr(VI) was 2.8%. The possible signal enhancement mechanism was proposed. The developed method has been applied to determine trace Cr(VI) in a variety of water samples. [ABSTRACT FROM AUTHOR]

• A novel strategy was developed to prepare nitrogen rich biochar. • APBC has high affinity and strong sorption ability towards Pb(II). • APBC contains abundant nitrogen and oxygen-containing groups. • Sorption of Pb(II) is mainly dominant by inner–sphere surface complexation. Biochar was prepared by torrefaction of ammonium persulphate pretreated bamboo (labeled as APBC) and applied into elimination of Pb(II) from water solutions. APBC was characterized by N 2 adsorption–desorption isotherms, elemental and Zeta potential analyses, SEM-EDS, XPS, and FTIR. Abundant N- and O-containing groups appeared atop APBC. Batch sorption assays revealed that APBC had high affinity and strong sorption ability towards Pb(II). The high Pb(II) adsorbing ability was attributed to the high contents of N- and O-containing functional groups of APBC. The adsorption mechanism mainly occurred by inner–sphere surface complexation. Hence, torrefaction of ammonium persulphate pretreated bamboo is a promising strategy for producing efficient biochar that is applicable for industrial wastewater treatment. [ABSTRACT FROM AUTHOR]

Cracks in tunnel lining structures constitute a common and serious problem that jeopardizes the safety of traffic and the durability of the tunnel. The similarity between lining seams and cracks in terms of strength and morphological characteristics renders the detection of cracks in tunnel lining structures challenging. To address this issue, a new deep learning-based method for crack detection in tunnel lining structures is proposed. First, an improved attention mechanism is introduced for the morphological features of lining seams, which not only aggregates global spatial information but also features along two dimensions, height and width, to mine more long-distance feature information. Furthermore, a mixed strip convolution module leveraging four different directions of strip convolution is proposed. This module captures remote contextual information from various angles to avoid interference from background pixels. To evaluate the proposed approach, the two modules are integrated into a U-shaped network, and experiments are conducted on Tunnel200, a tunnel lining crack dataset, as well as the publicly available crack datasets Crack500 and DeepCrack. The results show that the approach outperforms existing methods and achieves superior performance on these datasets., (© 2024. The Author(s).)

Background: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing., Objective: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control., Design: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994)., Setting: Three teaching hospitals in China from 27 May 2019 to 30 July 2022., Participants: 330 participants diagnosed with CSU., Intervention: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up)., Measurements: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores., Results: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient., Limitation: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period., Conclusion: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient., Primary Funding Source: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1043.

Background: An orally aerosolized adenovirus type-5 vector-based coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV) has recently been authorized for boosting immunization in China. Our study aims to assess the environmental impact of the use of aerosolized Ad5-nCoV., Methods: We collected air samples from rooms, swabs from the desks on which the vaccine nebulizer was set, mask samples from participants, and blood samples of nurses who administered the inoculation in the clinical trials. The viral load of adenovirus type-5 vector in the samples and the antibody levels against the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain in serum were detected., Results: Only one (4.00%) air sample collected before initiation of vaccination was positive and most air samples collected during and after vaccination were positive (97.96%, 100%, respectively). All nurses in trial A showed at least 4-fold increase of the neutralizing antibody against SARS-CoV-2 after initiation of the study. In trial B, the proportion of positive mask samples was 72.97% at 30 minutes after vaccination, 8.11% at day 1, and 0% at days 3, 5, and 7., Conclusions: Vaccination with the orally aerosolized Ad5-nCoV could result in some spillage of the vaccine vector viral particles in the environment and cause human exposure. Clinical Trials Registration. NCT04840992 and NCT05303584., Competing Interests: Potential conflicts of interest. P. W., T. Z., and X. L. L. are employees of CanSino Biologics Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster., Methods: This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 10 11 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 10 11 viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group vs homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing., Findings: Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% vs 9% and 14%, respectively; p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7-837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0-672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 [48·0-71·4]; p<0·0001)., Interpretation: A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac., Funding: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan., Competing Interests: Declaration of interests J-BG is an employee of CanSino Biologics. Tao Zhu owns stock in CanSino Biologics. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Nonresolving inflammation is a major driver of disease and needs to be taken seriously. Hypoxia-inducible factor (HIF) is closely associated with inflammation. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), as stabilizers of HIF, have recently been reported to have the ability to block inflammation. We used MK8617, a novel HIF-PHI, to study its effect on macrophage inflammation and to explore its possible mechanisms., Methods: Cell viability after MK8617 and lipopolysaccharide (LPS) addition was assessed by Cell Counting Kit-8 (CCK8) to find the appropriate drug concentration. MK8617 pretreated or unpretreated cells were then stimulated with LPS to induce macrophage polarization and inflammation. Inflammatory indicators in cells were assessed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunofluorescence (IF). The level of uridine diphosphate glucose (UDPG) in the cell supernatant was measured by ELISA. Purinergic G protein-coupled receptor P2Y 14 , as well as hypoxia-inducible factor-1α (HIF-1α) and glycogen synthase 1 (GYS1) were detected by qRT-PCR and WB. After UDPG inhibition with glycogen phosphorylase inhibitor (GPI) or knockdown of HIF-1α and GYS1 with lentivirus, P2Y 14 and inflammatory indexes of macrophages were detected by qRT-PCR and WB., Results: MK8617 reduced LPS-induced release of pro-inflammatory factors as well as UDPG secretion and P2Y 14 expression. UDPG upregulated P2Y 14 and inflammatory indicators, while inhibition of UDPG suppressed LPS-induced inflammation. In addition, HIF-1α directly regulated GYS1, which encoded glycogen synthase, an enzyme that mediated the synthesis of glycogen by UDPG, thereby affecting UDPG secretion. Knockdown of HIF-1α and GYS1 disrupted the anti-inflammatory effect of MK8617., Conclusions: Our study demonstrated the role of MK8617 in macrophage inflammation and revealed that its mechanism of action may be related to the HIF-1α/GYS1/UDPG/P2Y 14 pathway, providing new therapeutic ideas for the study of inflammation., Competing Interests: The authors declare that they have no competing interests., (© 2023 Qian et al.)

Background: Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine., Methods: We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 10 11 viral particles per mL; 0·1 mL; low dose group), or a high dose (1·0 × 10 11 viral particles per mL; 0·2 mL; high dose group) aerosolised Ad5-nCoV, or a homologous intramuscular vaccination with CoronaVac (0·5 mL). Only laboratory staff were masked to group assignment. The primary endpoint for safety was the incidence of adverse reactions within 14 days after the booster dose. The primary endpoint for immunogenicity was the geometric mean titres (GMTs) of serum neutralising antibodies (NAbs) against live SARS-CoV-2 virus 14 days after the booster dose. This study was registered with ClinicalTrials.gov, NCT05043259., Findings: Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p<0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p<0·0001)., Interpretation: We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination., Funding: National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The treatment of relapse or refractory multiple myeloma (RRMM) is still a big challenge in clinic. Recently, several clinical trials indicated that the XPO1 inhibitor, selinexor could significantly improve the remission rate in MM patients. However, the heterogeneous genetic background greatly influenced the efficiency of selinexor among MM. Here, we tried to characterized the biomarkers associated with selinexor sensitivity by analyzing gene expression data in MM patients. We found the cytogenetic background of selinexor sensitive MM patients was not limited to specific cytogenetic subtypes. In addition, by weighted gene co-expression network analysis (WGCNA), we obtained 10 key genes which showed a strong correlation with the selinexor sensitivity in MM patients. Notably, ABCC4 (MRP4) was the only gene which was both differentially expressed and proved to be clinical prognostic valuable (both for event-free survival and overall survival) in MM patients. We further validated the heterogenous expression of ABCC4 in MM cell lines and its value as a novel indicator for selinexor sensitivity. Moreover, immune infiltration analysis showed that ABCC4 expression had a significantly positive correlation with NK infiltration as well as immunotherapy target TIM-3 (HAVCR2) expression. Collectively, our findings indicated that ABCC4 might be a predictive biomarker of selinexor sensitivity in MM patients, which could be enhanced if combined with immunotherapy drugs such as TIM-3 inhibitor., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT., (© 2021. The Author(s).)

Background: This study aims to evaluate the efficacy and safety of detecting and removing residual common bile duct stones (CBDS) using direct peroralcholangioscopy (DPOC) after performing endoscopic retrograde cholangiopancreatography (ERCP) for stone retrieval., Methods: From January 5, 2017 to December 27, 2017, a total of 164 cases of choledocholithiasis were treated by ERCP for stone retrieval. According to the inclusion and exclusion criteria, the remaining 79 cases (39 males; mean age: 63.3 years old, range: 52-79 years old) were enrolled in the present study. The maximum transverse stone diameter was 6-15 mm (12.7 ± 4.2 mm), as determined by ERCP. Furthermore, there were 57 cases of multiple stones (number of stones: two in 41 cases, three in nine cases, and ≥ 4 in seven cases), 13 cases of post-mechanical lithotripsy, and nine cases of broken stones., Results: The overall success rate of DPOC was 94.9% (75/79). Furthermore, 18.7%(14/75) of cases were directly inserted, 72%(54/75) of cases required guide wire assistance, and 9.3%(7/75) of cases were successfully inserted with overtube assistance. The average insertion time was 7-17 min (4.9 ± 2.9 min). Residual stones were detected in 19 cases (25.3%), and all of which were < 5 mm in diameter. Moreover, five cases of formed stones were removed by basket and balloon catheter, while the remaining cases were cleaned after irrigation and suction. There were no serious complications., Conclusion: DPOC is safe and effective for both the detection and removal of residual CBDS after conventional ERCP.

The IL-2/IL-2 receptor (IL-2R) system plays a central role in maintaining normal T cell immunity, and its disturbance is associated with several hematologic disorders. Studies have found in several types of lymphoma that abnormal amounts of soluble IL-2R (sIL-2R) may result in imbalance of the IL-2/IL-2R system and hence of the T cell immunoregulation. Whether the level of sIL-2R in blood could predict treatment outcomes or not needs to be investigated in multiple myeloma (MM) patients. The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM. Twenty-six patients (32.1%) were treated with bortezomib-based regimens and 55patients (67.9%) received old drugs-based regimens. The mean concentration of sIL-2R for myeloma patients was 8.51 ng/ml, significantly higher than that of healthy controls (0.56 ng/ml, p < 0.0001). The best cutoff value for sIL-2R in predicting high risk for disease progression is 6.049 ng/ml with an area under curve (AUC) of 0.665 (p = 0.013). Thirty-six patients (44.4%) were classified as higher sIL-2R level group (> 6.049 ng/ml), and 45 patients (55.6%) as lower group (≤ 6.049 ng/ml). The overall response rate (ORR) was 60.0% in lower sIL-2R level group, and 41.7% in higher level group (p = 0.156). The median progression-free survival (PFS) and overall survival (OS) was 12 months (range, 2.0-65 months) and 20 months (range, 2.0-118 months), respectively. In a multivariate survival analysis, including Eastern Cooperative Oncology Group performance status score, treatment response, and sIL-2R level, it was found that all these three parameters were significantly independent prognostic factors for PFS (p = 0.032, 0.016, and 0.043, respectively), but none factors maintained their value in predicting OS. Subgroup analysis revealed that high level of sIL-2R is correlated with significantly inferior PFS in patients treated with bortezomib-based regimens (p = 0.004). Serum sIL-2R level is an independent prognostic factor for PFS, indicating novel drugs targeting the imbalance of IL-2/IL-2R system may be a promising strategy in MM.

Aim: Elevated neutrophil-to-lymphocyte ratio (NLR) has been demonstrated to be a poor prognostic factor in multiple types of malignancies, whereas the effect of NLR on the prognosis of epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) is not fully addressed., Methods: 81 metastatic NSCLC patients harboring EGFR mutation treated with first-line EGFR TKIs were retrospectively included. The associations between baseline clinical characteristics, including NLR, and tumor response, progression and survival were investigated., Results: Elevated NLR (≥3.5) was observed in 33 of 81 patients. The progression-free and overall survival of the patients with increased NLR was significantly worse than that of the patients with decreased NLR (8.20 vs 10.60 months, P < 0.001 and 17.20 vs 23.20 months, P < 0.001, respectively). Elevated NLR was confirmed to be an independent prognostic factor for worse progression-free and overall survival in Cox multivariate analysis., Conclusion: Elevated NLR is likely to be associated with poor outcome in EGFR-mutated advanced NSCLC patients treated with first-line EGFR TKIs., (© 2014 Wiley Publishing Asia Pty Ltd.)

In the presence of TMSCl, the [3 + 2] cycloaddition of oxazol-5-(4H)-ones with nitrones proceeded smoothly and furnished the desired isoxazolidin-5-ones with high diastereoselectivities in reasonable chemical yields. The chemical structure of the title compounds was firmly confirmed by X-ray single-crystal structure analysis.

Patients with stage IE/IIE natural killer T (NK/T) cell lymphomas have discrepant survival outcome. This study aims to establish a prognostic model based on the pretreatment platelet lymphocyte ratio (PLR) specifically for localized extranodal NK/T cell lymphoma to guide the therapy. We retrospectively analyzed the data of 252 patients with early-stage upper aerodigestive tract NK/T cell lymphoma. The 5-year overall survival rate in 252 patients was 67.1%. Prognostic factors for survival were female (P = 0.025; relative risk, 0.51; 95% CI 0.28-0.92), older age (P = 0.000; relative risk, 3.34; 95% CI 1.94-5.75), stage II(P = 0.020; relative risk, 1.79; 95% CI 1.10-2.91), lactate dehydrogenase (LDH) level (P = 0.009; relative risk, 2.00; 95% CI 1.19-3.35), and PLR (P = 0.020; relative risk, 1.77; 95% CI 1.10-2.87). Based on these five parameters, we identified three different risk groups: group 1(106 cases, 43.4%), no or one adverse factor; group 2(85 cases, 34.8%), two factors; group 3(53 cases, 21.7%), three to five factors. Five-year overall survival was 83.3% for group 1, 62.2% for group 2, and 43.1% for group 3 (P = 0.000). Compared with International Prognostic Index and Korean Prognostic Index, the new model has a better prognostic discrimination for the patients of stage IE/IIE upper aerodigestive tract NK/T cell lymphoma. The PLR-based prognosis model is useful to stratify patients with localized extranodal NK/T cell lymphoma into different risk groups and guide the treatment modalities selection.

Inflammation has been demonstrated to be widely involved in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the prognostic significance of lymphocyte to monocyte ratio (LMR) in metastatic NPC is not fully addressed. The purpose of the study is to investigate the prognostic impact of pre-treatment absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR on patients with newly diagnosed metastatic NPC undergoing chemotherapy. Between January 2006 and December 2010, patients with newly diagnosed metastatic NPC undergoing chemotherapy were retrospectively collected. The prognostic significance of baseline clinical features and inflammatory markers was investigated. A total of 256 patients were eligible for the study. The best cut-off value of ALC, AMC, and LMR was 2.25 × 10(9)/L, 0.35 × 10(9)/L, and 5.07, respectively. Patients in the high LMR group had a significantly longer overall survival (OS) (25.0 months [24.50-25.49]) than patients in the low LMR group (16.0 months [15.51-16.49]; p < 0.001). In addition, ALC ≥ 2.25 × 10(9)/L (HR, 0.59; 95% CI, 0.43-0.81; p = 0.001) and LMR ≥ 5.07 (HR, 0.42; 95% CI, 0.30-0.59; p <  .001) remained as independent prognostic factors for superior OS, while AMC did not retained its prognostic significance in COX multivariate analysis. Pre-treatment ALC and LMR were demonstrated to be independent prognostic factors in patient with newly diagnosed metastatic NPC receiving chemotherapy. Future prospective studies are needed to validate the findings.

Interest in carbon nanotubes for detecting the presence of pathogens arises because of developments in chemical vapor deposition synthesis and progresses in biomolecular modification. Here we reported the facile synthesis of multi-walled carbon nanotubes (MWCNTs), which functioned as immuno-, magnetic, fluorescent sensors in detecting Vibrio alginolyticus (Va). The structures and properties of functionalized MWCNTs were characterized by ultraviolet (UV), Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), magnetic property measurement system (MPMS) and fluorescent spectra (FL). It was found that the functionalized MWCNTs showed: (1) low nonspecific adsorption for antibody-antigen, (2) strong interaction with antibody, and (3) high immune-magnetic activity for pathogenic cells. Further investigations revealed a strong positive linear relationship (R=0.9912) between the fluorescence intensity and the concentration of Va in the range of 9.0 × 10(2) to 1.5 × 10(6) cfum L(-1). Moreover, the relative standard deviation for 11 replicate detections of 1.0 × 10(4) cfum L(-1) Va was 2.4%, and no cross-reaction with the other four strains was found, indicating a good specificity for Va detection. These results demonstrated the remarkable advantages of the multifunctional MWCNTs, which offer great potential for the rapid, sensitive and quantitative detection of Va in fishery and environmental samples., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The acrylate-like materials were used to develop the polymer coated controlled release fertilizer, the nutrients release profiles were determined, meanwhile the Fourier transform mid-infrared photoacoustic spectra of the coatings were recorded and characterized; GRNN model was used to predict the nutrients release profiles using the principal components of the mid-infrared photoacoustic spectra as input. Results showed that the GRNN model could fast and effectively predict the nutrient release profiles, and the predicted calibration coefficients were more than 0.93; on the whole, the prediction errors (RMSE) were influenced by the profiling depth of the spectra, the average prediction error was 10.28%, and the spectra from the surface depth resulted in a lowest prediction error with 7.14%. Therefore, coupled with GRNN modeling, Fourier transform mid-infrared photoacoustic spectroscopy can be used as an alternative new technique in the fast and accurate prediction of nutrient release from polymer coated fertilizer.

Objective: To explore the best intervention time of acupuncture and moxibustion for peripheral facial palsy (Bell's palsy) and the clinical advantage program of selective treatment with acupuncture and moxibustion., Methods: Multi-central large-sample randomized controlled trial was carried out. Nine hundreds cases of Bell's palsy were randomized into 5 treatment groups, named selective filiform needle group (group A), selective acupuncture + moxibustion group (group B), selective acupuncture + electroacupuncture (group C), selective acupuncture + line-up needling on muscle region of meridian group (group D) and non-selective filiform needle group (group E). Four sessions of treatment were required in each group. Separately, during the enrollment, after 4 sessions of treatment, in 1 month and 3 months of follow-up after treatment, House-Brackmann Scale, Facial Disability Index Scale and Degree of Facial Nerve Paralysis (NFNP) were adopted for efficacy assessment. And the efficacy systematic analysis was provided in view of the intervention time and nerve localization of disease separately., Results: The curative rates of intervention in acute stage and resting stage were 50.1% (223/445) and 52.1% (162/311), which were superior to recovery stage (25.9%, 35/135) separately. There were no statistical significant differences in efficacy in comparison among 5 treatment programs at the same stage (all P > 0.05). The efficacy of intervention of group A and group E in acute stage was superior to that in recovery stage (both P < 0.01). The difference was significant statistically between the efficacy on the localization above chorda tympani nerve and that on the localization below the nerve in group D (P < 0.01). The efficacy on the localization below chorda tympani nerve was superior to the localization above the nerve., Conclusion: The best intervention time for the treatment of Bell's palsy is in acute stage and resting stage, meaning 1 to 3 weeks after occurrence. All of the 5 treatment programs are advantageous to Bell's palsy. In the condition of the limited medical sources, the simple filiform needle therapy is recommended in acute stage. For the patients with the disorder above chorda tympani nerve, the line-up needling on muscle region of meridian is not recommended.

Hypoxia is recognized as an important factor contributing to cancer development and drug resistance. Cetuximab, a chimeric monoclonal antibody to EGFR, is known to inhibit HIF-1 alpha expression levels and to enhance the cytotoxicity of chemotherapeutic agents. We demonstrated that hypoxia induced drug resistance in gastric cancer cells. Cetuximab enhanced oxaliplatin-induced cytotoxicity and apoptosis in normoxia and caused a reversal of drug resistance in hypoxia. Normoxic and hypoxic gastric cancer cells were treated with cetuximab, oxaliplatin or the combination and assessed for cell growth, proliferation, and apoptosis. Combination treatment resulted in a marked inhibition of HIF-1 alpha expression levels in hypoxic cells and caused a significant reduction in the expression of activated phosphorylated AKT, ERK1/2, p-BAD and VEGF in both normoxia and hypoxia with greater levels of inhibition in hypoxia. In summary, cetuximab inhibits HIF-1 alpha expression via the MAPK/ERK and PI3K/AKT signaling pathways and functions to overcome drug resistance induced by hypoxia. Cetuximab-oxaliplatin combination therapy may therefore emerge as an attractive treatment strategy for advanced gastric cancer.

Background and Objective: Adjuvant chemotherapy has become a standard postoperative treatment for stage III and high risk stage II colorectal carcinoma patients. However, only a few patients can finish 6-month adjuvant chemotherapy. This study was to find out whether the duration of adjuvant chemotherapy would affect the 3-year disease-free survival., Methods: Clinical data of 276 colorectal carcinoma patients, receiving at least two cycles of adjuvant chemotherapy including xeloda, 5-fluorouracil/calcium folinate (5-FU/CF) or Tegafur with or without oxaliplatin after radical operation in Sun Yat-sen University Cancer Center from April, 2003 to December, 2007, were analyzed for the impact of adjuvant chemotherapy duration on the 3-year disease-free survival., Results: Of the 276 patients, 216 received chemotherapy including oxaliplatin, 60 received xeloda, 5-FU/CF or tegafur as adjuvant chemotherapy. Of the 216 patients, only 49 finished the 6-month adjuvant chemotherapy. Both univariate and multivariate analyses showed that chemotherapy duration (P=0.032), sex (P=0.001), N stage (P=0.002), and pathologic differentiation (P=0.043) were independent prognosis factors for 3-year disease-free survival., Conclusion: Duration of adjuvant chemotherapy is an independent prognosis factor for 3-year disease-free survival of colorectal carcinoma patients.

Background and Objective: The incidence of intrahepatic cholangiocarcinoma (ICC) is low. Current treatment for ICC is unsatisfied. This study was to investigate the prognosis of patients with resectable or unresectable ICC., Methods: Clinical data of 84 patients with pathologically confirmed ICC treated at Cancer Center, Sun Yat-sen University from January 1997 to December 2007 were reviewed. Survival and prognosis were analyzed by Kaplan-Meier method and Cox regression model., Results: Of the 84 patients, 56 (66.7%) had resectable ICC, and 28 (33.3%) had unresectable ICC. Among the 56 patients with resectable ICC, 27 (48.2%) underwent radical resection, and 29 (51.8%) underwent palliative resection. The 2-year overall survival rate was 3.1% in unresectable ICC group; it was significantly higher in radical resection group than in palliative resection group (P<0.01). For the patients with resectable ICC, univariate analysis revealed that operation pattern, histological type, tumor size and number, lymph node metastasis, intrahepatic metastasis, portal vein thrombus, postoperative serum level of albumin, preoperative serum levels of CEA, CA199, TBIL, ALT and AST were related to the prognosis; multivariate analysis found that operation pattern, histological type, tumor number, preoperative serum levels of CEA, CA199 and TBIL were independent prognostic factors. For the patients with unresectable ICC, univariate analysis found that histological type and preoperative serum level of CA199 were related to the prognosis; whereas multivariate analysis found that histological type was the only independent prognostic factor. Chemotherapy showed no survival benefit in both resectable and unresectable ICC groups (P=0.30, P=0.78)., Conclusions: Radical resection is the main effective treatment for ICC patients to achieve long-term survival. Preoperative serum levels of CEA, CA199 and TBIL are significant prognostic factor for patients with resectable ICC.

Erythropoietin (EPO) has firstly known to regulate cell proliferation and differentiation along the erythroid lineage. Recent studies have shown that EPO, a pleiotropic cytokine, is proangiogenic and exerts broad tissue-protective effects in diverse nonhematopoietic organs. A series of studies have documented the expression of EPO and EPO receptor (EPO-R) in various cancer cells. The presence of an autocrine-paracrine EPO/EPO-R system may associate with the potential for stimulation of tumor neoangiogenesis and tumor proliferation, inhibition of apoptosis, or modulation of sensitivity to chemoradiotherapy. The complex mechanism needs further research. Recombinant human erythropoietin (rh-EPO) has been widely used in clinic to treat malignancy-associated anemia. Clinical trials have documented the efficacy of rh-EPO in increasing hemoglobin levels, reducing red blood cell (RBC) transfusion requirements and improving quality of life in cancer patients. However, three randomized trials reported negative outcomes with rh-EPO, as patients in the rh-EPO arm fared worse than their placebo-treated counterparts with progression-free survival. This review described EPO and EPO-R biology, focusing on the expression, pleiotropic function and mechanism on nonhematopoietic tissues especially on cancer cells.