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Herein, we report the first rhodium-catalyzed hydrolytic cleavage of the silicon-carbon bond in silacyclobutanes using water as the reactant. A series of silacyclobutanes could be employed in this reaction in the presence of the Rh/BINAP complex, resulting in the corresponding silanols in good yields. Additionally, a chiral 1,1,4,4-tetraaryl-2,3- O -isopropylidene-l-threitol-derived phosphoramidite ligand could be used in this reaction to yield Si-stereogenic silanol with promising enantioselectivity.

Given the powerful potential of chiral-at-silicon chemistry, enantioselective synthesis of Si-stereogenic centers has attracted substantial research interest in recent years. However, the catalytic asymmetric synthesis of Si-stereogenic organosilicon compounds remains an appealing venture and is a challenging subject because of the difficulty in achieving high reactivity and stereoselectivity for "silicon-center" transformations. Herein, we disclose a highly enantioselective palladium-catalyzed hydrosilylation of 1,3-diynes with dihydrosilanes, which enables the facile preparation of Si-stereogenic enynes and an enyne-linked chiral polymer (polyenyne) in good yields and excellent ees (up to >99%) by desymmetrization. The unusual stereoselectivity in this reaction is achieved by precisely controlling the steric hindrance and electronic effect of the newly developed chiral ligands, resulting in a wide range of chiral silanes and a Si-containing polymer bearing a Si-stereogenic center which is otherwise difficult to access. The key to the high enantioselectivity relies on catalyst aggregation-induced non-covalent interaction, which exerts a remarkably positive influence on the Si-H bond activation and enhancement of enantioselectivity, in which the palladium/P-ligand complex was proved to be air-stable and moisture-insensitive in this reaction., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Strategies on the construction of enantiomerically pure silicon-stereogenic silanes generally relies on desymmetrization of prochiral and symmetric substrates. However, dynamic kinetic asymmetric transformations of organosilicon compounds have remained underdeveloped and unforeseen owing to a lack of an effective method for deracemization of the static silicon stereocenters. Here we report the first Rh-catalyzed dynamic kinetic asymmetric intramolecular hydrosilylation (DyKAH) with "silicon-centered" racemic hydrosilanes that enables the facile preparation of silicon-stereogenic benzosiloles in good yields and excellent enantioselectivities. The special rhodium catalyst controlled by non-diastereopure-type mixed phosphine-phosphoramidite ligand with axial chirality and multiple stereocenters can induce enantioselectivity efficiently in this novel DyKAH reaction. Density functional theory (DFT) calculations suggest that the amide moiety in chiral ligand plays important role in facilitating the S N 2 substitution of chloride ion to realize the chiral inversion of silicon center., (© 2022 Wiley-VCH GmbH.)

Background: Oblique lateral lumbar interbody fusion (OLIF) is one of the most widely used lumbar interbody fusion procedures in clinical practice. The aim of this study was to minimize the incidence rate of surgical complications by measuring the anatomical parameters of structures surrounding the working channels of OLIF with 3D COSMIC sequence., Methods: The MRI examination included conventional MRI sequence and 3D COSMIC sequence. Surgical window, psoas thickness, the transverse diameter of the endplate, and nerve distance were measured to evaluate the anatomical characteristics surrounding the OLIF working channels., Results: The widths of the natural surgical window at the level of the L2-3, L3-4, and L4-5 intervertebral measured in this study were 16.25 ± 4.22, 15.46 ± 4.64 mm, and 11.71 ± 6.29 mm, respectively. The average thickness of the left psoas major muscle at the level of L2-3, L3-4, and L4-5 intervertebral space was 28.42 ± 5.08 mm, 30.76 ± 5.84 mm, and 31.16 ± 7.72 mm, respectively. The mean value of insertion angle (β) was 45.57° ± 6.19° in L2-3 intervertebral space, 49.90° ± 6.53° in L3-4 intervertebral space, and 43.34° ± 8.88° in L4-5 intervertebral space., Conclusions: The 3D COSMIC sequences can be used for imaging anatomical assessment before OLIF surgery. In preoperative planning, the 3D COSMIC sequence can be used to measure the relevant parameters mentioned above to optimize the planned surgical approach., (© 2022. The Author(s).)

Aim: This study aimed to investigate eHealth literacy about coronavirus disease 2019 (COVID-19) among older adults during the pandemic., Background: The COVID-19 pandemic promoted the development of online health care. Higher demand for accessing information from the Internet was seen., Methods: This was a sequential explanatory mixed-method study, involving a survey of older adults to explore the status and influencing factors of eHealth literacy regarding COVID-19. Semi-structured interviews were used to understand experiences and challenges regarding information retrieval, judgment and utilization., Results: A total of 337 older adults participated in the online questionnaire survey. Overall, older adults had slightly higher scores on eHealth literacy during the COVID-19 pandemic. Participants' location in the past month and current health issues were associated with eHealth literacy. Qualitative data were collected from nine older adults and included that some older adults retrieved health-related information during the pandemic. However, those who used non-smartphones described difficulties in information retrieval. A glut of misinformation has resulted in an 'infodemic', which has not only increased the difficulty of judging information but also posed challenges in information utilization for older adults., Conclusion: Improving older adults' eHealth literacy is essential in promoting an improved response to major public health events and in providing better health care for this group in the future. It is essential that government health agencies and health care providers provide evidence-based health information via social media platforms. Further efforts are needed to combine aspects of traditional and online health care services and provide reliable and updated online information and resources for older adults., Implications for Nursing Management: Providing evidence to eHealth literacy improvement and health management of older adults in the context of public health events., (© 2022 John Wiley & Sons Ltd.)

Background: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL., Methods: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm., Results and Conclusions: Univariate and multivariate analyses revealed that platelets< 254 × 10 9 /L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL., (© 2022. The Author(s).)

College students are one of the most important groups of participants and promoters of household waste separation. Taking Ningbo as a case study, an online + offline questionnaire survey among more than 1700 students in 10 colleges is conducted to identify the main factors and pathways influencing waste separation behavior in the post COVID-19 pandemic period. The results show that the KMO statistic is 0.926, Bartlet test is p  < 0.001, indicating that questionnaire sample data is suitable for factor analysis. The modified Structural Equation Model test indicates that waste separation behavior of college students mainly results from the combined effect of eight subjective intrinsic factors and seven external situational factors. Among them, the convenience of recycling facilities, the convenience of sorting facilities and the publicity and education of sorting knowledge are the top three factors with the most significant influence. The mean value of epidemic impact factors is 0.277, which is slightly lower than conventional influence factors (0.289). Environmental Norms and Constraints are an essential component in the analysis framework of college students' waste separation behavior. In the future, society and colleges should give full play to the positive influence of the epidemic factor on college students' waste separation behavior., Supplementary Information: The online version contains supplementary material available at 10.1007/s10163-022-01363-3., (© Springer Japan KK, part of Springer Nature 2022.)

Purpose: With programmed cell death 1 (PD-1) inhibitors approved for second-line treatment of advanced esophageal cancer, immunotherapy and chemotherapy have gradually become the main treatments for second-line treatment of patients with advanced esophageal cancer (AEC). This meta-analysis and systematic review were conducted to evaluate the efficacy and safety of PD-1 inhibitors monotherapy versus chemotherapy in second-line treatment of AEC., Methods: Eligible randomized controlled trials were searched in PubMed, Embase, and the Cochrane Library and abstracts presented at the American Society of Clinical Oncology or European Society of Medical Oncology were reviewed to assess the efficacy and tolerability of PD-1/programmed cell death ligand 1 (PD-L1) inhibitors relative to chemotherapy for AEC from January 2016 to October 2020. Patients diagnosed with AEC and progressing after first-line therapy were included in this study. Hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) of objective response rate (ORR), and the odds ratios (ORs) of adverse effects (AEs) were calculated., Findings: The study included 4 randomized controlled trials with 1683 patients. The results indicated that PD-1 inhibitors prolonged the OS (HR = 0.79; 95% CI, 0.71-0.88; P < 0.01) and improved the ORR (RR = 3.00; 95% CI, 2.36-3.82; P = 0.01) but did not improve the PFS (HR = 0.96; 95% CI, 0.76-1.20; P = 0.692) compared with chemotherapy in the second-line treatment of AEC. PD-1 inhibitors alone were associated with a lower incidence of all treatment-related AEs (OR = 0.29; 95% CI, 0.09-0.89; P = 0.03) and grade 3 to 5 treatment-related AEs (OR = 0.26; 95% CI, 0.16-0.44; P < 0.01) versus chemotherapy. PD-1 inhibitors prolonged OS mainly in the following patient groups: male, age <65 years, Eastern Cooperative Oncology Group performance status of 1, or PD-L1 tumor proportion score ≥10%. Asian patients had a longer OS than non-Asian patients (P = 0.01)., Implications: The available evidence indicates that the efficacy and tolerability of PD-1 inhibitors were better than chemotherapy in the second-line treatment of AEC, and the benefiting population of these patients was limited to males, those <65 years of age, those with a Eastern Cooperative Oncology Group performance status of 1, or those with a PD-L1 tumor proportion score ≥10%. Notably, Asian patients receiving immune monotherapy had longer OS than non-Asian patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the associations between medical check-up items (MCI) for fundus and intraocular pressure abnormality (FIPA) diseases in the Department of Health Management Centre, the Fifth Affiliated Hospital of Sun Yat-sen University (DHMC-FHS)., Patients and Methods: Individuals who visited DHMC-FHS and underwent MCI between June 2017 to May 2019 were included, 3237 subjects. A total of 356 participants were diagnosed as FIPA and enrolled. The general clinical characteristics were collected. Diseases for FIPA diagnosed included five cohort, high intraocular pressure, diabetic retinopathy, hypertension fundus arteriosclerosis, large eye cup, and high myopia fundus changes. Possible impact factors of MCI included blood routine, B-ultrasound, heart rate, hypertension, hyperlipidemia, standard vision, cerebral arteriosclerosis, body mass, arterial/carotid arteriosclerosis, etc. Further, the Pearson's correlation coefficients and logistic regression analyses were used to examine associations between MCI and FIPA., Results: The weighted study population who belonged to FIPA included 356 subjects. There were significant differences in age, IOP, habitual exercise, smoking, sleep duration ( P ˂0.05) between FIPA and without FIPA. And RBC, Hemoglobin, B-ultrasound abnormal event, heart rate, systolic pressure, diastolic pressure, TC, LDL-C, standard vision, cerebral arteriosclerosis, body mass index, carotid arteriosclerosis were positively correlated with high intraocular pressure, hypertension fundus arteriosclerosis and high myopia fundus changes ( P < .05). Possible prognosis risk factors, higher IOP, habitual exercise and more frequent smoking affect FIPA prognosis significantly [Odds ratio (OR) = 0.53, P = .01; OR = 0.13, P = .03; OR = 0.83; P = .04, respectively]., Conclusion: Of FIPA participants, high intraocular pressure, hypertension fundus arteriosclerosis and high myopia fundus changes were shown a positive relationship with MCI. Control IOP, habitual exercise and less frequent smoking were regarded as positive associations with decreased FIPA. These findings could help us prevent and diagnose FIPA diseases in time via MCI.

For follicular lymphoma (FL) with grade 1/2, the complete response (CR) rate of the first-line R-CHOP treatment was significantly low. In this study, we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses. Thus, we conducted a prospective pharmacokinetic (PK) study in 68 FL patients with grades 1-3 treated with R-CHOP at 21-day intervals. Plasma rituximab concentrations were quantified using ELISA and the population PK modeling was established with Phoenix ® NLME TM . The first cycle trough concentration (C 1-trough ) of rituximab was a significant independent risk factor for achieving CR in matched-pair logistic regression analysis, rather than the concentrations in later cycles; the recommendatory minimum optimal C 1-trough was 13.60 μg/mL. Patients with grade 1/2 had significantly lower C 1-trough compared with grade 3 (12.21 μg/mL vs. 23.45 μg/mL, P < 0.001), only 30% patients with grade 1/2 could reach 13.60 μg/mL, compared with 91.67% in patients with grade 3, which was in accord with its unsatisfactory CR rates (43.33% vs. 76.32%). The stage indicating the tumor burden (the target) was a crucial influence factor for C 1-trough , accounting for 40.70% of its variability, 70% patients with grade 1/2 were stage IV in this study, since the systemic therapy only started at the disseminated disease stage. The initial dose of 1800 mg was recommended by Monte Carlo simulation for patients with grade 1/2. In summary, low C 1-trough accounted for low-grade FL's unsatisfactory CR rate, designing the first dosage of rituximab should be a very important component of individualized therapy for FL.

Our aim was to explore the role of crizotinib, targeted anaplastic lymphoma kinase (ALK), on r/r systemic anaplastic large cell lymphoma (sALCL). The treated group prospectively screened 20 patients. After taking crizotinib in the first week, 16 patients who were tolerant and sensitive received the combination of crizotinib with chemotherapy. The control group included 27 patients receiving chemotherapy in the same hospital during the same period. The objective remission rates of the treated and control group were 81.3% and 74.1% ( p  = .869), respectively. The progression-free survival rates at two years in treated and control group were 68.7% and 45.0% (HR = 0.42, 95% CI 0.17-0.99, p  < .05), respectively. The overall survival rates at two years in the treated and control group were 86.1% and 78.9% ( p  = .385, HR = 0.51, 95% CI 0.11-2.30), respectively. The main adverse events included elevated transaminase, diarrhea, and vision abnormalities. Thus, the combination of crizotinib with chemotherapy might be effective in ALK-positive and crizotinib sensitive r/r sALCL patients.

Objective: The main aim of this study was to systematically evaluate the efficacy and safety of inhibitors of programmed cell death receptor 1 (PD-1) and its ligand, programmed cell death ligand-1 (PD-L1), in the treatment of advanced non-small cell lung cancer (NSCLC)., Methods: Randomized controlled trials assessing the efficacy of PD-1/PD-L1 inhibitors relative to platinum-based chemotherapy for advanced NSCLC in PubMed, EMBASE, and Cochrane libraries from 2015 to 2020 were searched, along with review of studies at American Society of Clinical Oncology (ASCO) and European society for Medical Oncology (ESMO). Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) and odds ratios (OR) for adverse events (AE) were calculated using STATA and Revman software., Results: PD-1/PD-L1 inhibitors alone or combined with chemotherapy significantly improved OS (HR = 0.82, 95% CI:0.74-0.91, P = 0.01 or HR = 0.74, 95% CI:0.67-0.82, P = 0.001). PD-1/PD-L1 inhibitors alone did not benefit PFS (HR = 0.99, 95% CI: 0.89-1.10, P = 0.892), while combination therapy led to prolonged PFS (HR = 0.61, 95% CI: 0.56-0.67, P < 0.001). Subgroup analysis showed that in NSCLC with PD-L1 ≥ 50%, treatment with PD-1/PD-L1 inhibitors alone significantly improved both PFS and OS. In patients subjected to the combined treatment regimen, we observed significant differences in PFS among groups stratified by PD-L1 expression (p < 0.001), immune drug type (p = 0.029), gender (p = 0.014) and liver metastasis (p = 0.035) and OS among groups stratified by immune drug type (p < 0.001), gender (P = 0.001) and smoking status (P = 0.041). Safety analysis showed that combination therapy increased chemotherapy-induced adverse events (AE), while PD-1/PD-L1 inhibitors alone were associated with a lower incidence of any grade of treatment-related AEs (TRAE). A higher incidence of Grade 3-5 TRAEs and hypothyroidism was observed with PD-1 inhibitors than PD-L1 inhibitors., Conclusions: First-line treatment of advanced NSCLC with immune monotherapy or immunochemotherapy confers a greater survival benefit than chemotherapy alone. Combination of chemotherapy with PD-1/PD-L1 inhibitors leads to an increase in adverse events, and PD-1 inhibitors offer enhanced survival benefits and fewer adverse events than PD-L1 inhibitors. Remarkably, female patients undergoing combination therapy had longer overall survival than male patients., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare and extremely malignant tumor. The systemic inflammation score (SIS), which is based on the pretreatment level of lymphocyte-to-monocyte ratio (LMR) and serum albumin (Alb), has been shown to be of prognostic value in a number of cancers. We integrate several other pretreatment serum inflammatory indicators, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), serum C-reactive protein (CRP) and albumin (Alb) level, to establish a modified systemic inflammatory scoring system to predict clinical outcomes of ENKTL., Methods: A total of 184 patients with newly diagnosed ENKTL was retrospectively investigated. Systemic inflammatory indexes, including NLR, LMR, CRP, and Alb level were reviewed. Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off value. The associations between cutoff values and overall survival (OS) were analyzed by Kaplan-Meier curves and Cox proportional models., Results: The median age of patients was 44.0 years, ranging from 15 to 82 years. There were 129 (70.1%) male patient. About 57.1% of patients had stage III or IV disease. The optimal cut-off values of NLR and LMR in predicting OS were 3.1 and 2.4, respectively. The clinical standard of CRP and Alb levels at 10 and 40 mg/L, respectively, were chosen as the optimal cut-off values. By multivariate analysis, hemophilic syndrome (hazard ratio [HR]: 10.540, 95% confidence interval [CI]: 3.440-32.291, P < 0.001), advanced Ann Arbor stages (III-IV) (HR: 4.606, 95% CI: 1.661-12.774, P = 0.003), paranasal sinus invasion (HR: 2.323, 95% CI: 1.069-5.047, P = 0.033), NLR ≥ 3.1 (HR: 3.019, 95% CI: 1.317-6.923, P = 0.009), Alb level of <40 mg/L (HR: 0.350, 95% CI: 0.134-0.915, P = 0.032), and radiation therapy (HR: 0.430, 95% CI: 0.205-0.901, P = 0.025) were independent protective factors for ENKTL. We combined two inflammatory indexes NLR and Alb level to establish a modified systemic inflammation score (mSIS). These 184 patients were divided into 3 groups: group 1 (mSIS score of 0), group 2 (mSIS score of 1), and group 3 (mSIS score of 2). The mean OS of these three groups were 42 months (95% CI: 31.4-53.12), 77 months (95% CI: 68.5-87.5), and 89 months (95% CI: 71.4-82.7), respectively (P < 0.001). The Harrell's concordance index (C-index) of mSIS is 0.725. The mSIS could be used to discriminate patients categorized in the low-risk group of International Prognostic Index (IPI) (P < 0.001) and the low-risk and intermediate-risk prognostic index of natural killer cell lymphoma (PINK) group (P = 0.019)., Conclusion: The pretreatment mSIS could be an independent prognostic factor for OS in patients with ENKTL and warrants further research., (Copyright © 2020 Huang, Chen, Fang, Guo, Lin, Hong, Li, Wang, Tian, Chen, Yao, Chen, Li and Pan.)

Renal cell carcinoma (RCC) is not sensitive to conventional radiotherapy and chemotherapy, and the effectiveness rate of molecular targeted therapy is low. Therefore, it is urgent to identify new treatment methods. Recently, adoptive T‑cell therapy has provided a new option for cancer treatment. Furthermore, low‑dose chemotherapy not only has no evident side effects and inhibitory effects on the human immune system, but can also enhance the immune activity of some effector cells. Therefore, it is surmised that the combination of different mechanisms of chemotherapy and immunotherapy could be a new treatment concept. In the present study, the effects of low‑dose chemotherapy combined with T cells in the treatment of renal cell carcinoma were explored using cytotoxicity assays, enzyme‑linked immunosorbent assay (ELISA), western blot analysis and flow cytometric analysis. The results revealed that low‑dose chemotherapy and T cells had synergistic effects on tumor cell elimination in vitro. The transforming growth factor (TGF)‑β signaling pathway may be involved in the inhibition of T‑cell functions. The targeted inhibition of TGF‑β signals may be a promising therapeutic strategy for the treatment of renal cancer. The present results provided a novel strategy for the combination of low‑dose chemotherapy and T cells to enhance the therapeutic efficacy of RCC treatment.

The aim of the present meta-analysis was to evaluate the effect of vitamin D supplementation on patients with polycystic ovary syndrome (PCOS). A literature search was performed to identify all of the relevant studies comparing the effect of vitamin D supplementation with placebo in PCOS patients, in the PubMed, Embase and Web of Science databases. All statistical analyses were performed on case-control studies using Review Manager 5.3 software, provided by the Cochrane Collaboration. A total of 11 studies involving 483 participants were included in the current meta-analysis. Vitamin D supplementation appeared to lead to an improvement in the levels of total testosterone [weighted mean differences (WMD) = -0.10, 95% CI (-0.18, -0.02)], homeostasis model assessment of insulin resistance [WMD = -0.44, 95% CI (-0.86, -0.03)], homeostasis model assessment of β-cell function [WMD = -16.65, 95% CI (-19.49, -13.80)], total cholesterol [WMD = -11.90, 95% CI (-15.67, -8.13)] and low-density lipoprotein-cholesterol [WMD = -4.54; 95% CI (-7.29, -1.80)]. The results failed to show a positive effect of vitamin D supplementation on the body mass index, dehydroepiandrosterone sulfate, triglyceride levels or high-density lipoprotein-cholesterol. In conclusion, the data from the available randomized controlled trials (RCTs) suggested vitamin D supplementation reduced insulin resistance and hyperandrogenism, as well improving the lipid metabolism of patients with PCOS to an extent. Further high-quality RCTs from a variety of regions in the world are required to determine the effectiveness of vitamin D supplementation in PCOS patients, and to determine a suitable dose and unit of vitamin D., (Copyright: © Miao et al.)

Objective: To summarize the clinical, video electroencephalogram (VEEG), radiological and pathological features of 3 patients of temporal lobe epilepsy (TLE) with amygdala enlargement (AE)., Methods: Three TLE patients with AE who were hospitalized in Peking University International Hospital were collected. The above features were retrospectively analyzed, and the amygdala volume was measured as well., Results: Of all the 3 patients, 2 were females and 1 male, whose seizure onset ages varied from 21 to 40 years. Two cases presented with secondarily generalized tonicclonic seizures after falling asleep during the night. One of the 2 cases had complex partial seizures (CPSs) with episodic memory and automatism after one year, and the third one had CPSs with lip smacking and tongue wagging during the night. All the patients suffered from obvious anxious disorder. Unilateral AE by MRI was demonstrated in the 3 cases, one on the right side, and the other two on the left side. The average amygdala volume of the enlarged side and the other side were (2 123.7±131.8) mm 3 and (1 276.3±156.9) mm 3 , respectively. Unilateral interictal epileptic discharges were ipsilateral to the AE in 2 cases, while the other patient showed bilateral interictal epileptic discharges. The ictal VEEG showed that the seizure onset zone was ipsilateral to the AE and was confined to the anterior and middle temporal regions in the 3 patients. The interictal single-photon emission computed tomography (SPECT) was negative in 2 cases. The interictal positron emission tomography (PET) showed hypometabolism in the AE in one case. The histological pathology revealed focal cortical dysplasia in the amygdala and temporal lobe in the 3 cases, and one of the 3 cases was combined with hippocampal sclerosis. All the patients became seizure free after surgery in the half year following-up. VEEG revealed slow wave activity and occasional spike wave in the operated side., Conclusion: AE may be one subtype of TLE. It is necessary to recognize AE in TLE with MRI-negative. For those poorly responsive to antiepileptic drugs, surgical treatment could provide a better solution. Focal cortical dysplasia may be one of the most common pathological features of TLE with AE.

Objective: A retrospective observational cohort study was conducted to evaluate the efficacy and safety of tacrolimus in Osserman grade III and Osserman grade IV myasthenia gravis (MG) patients., Patients and Methods: MG patients admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2011 and January 2017 with grade III and grade IV according to the modified Osserman scale were recruited and received a telephone follow-up in September 2017. Patients treated with tacrolimus plus prednisone were compared with those treated without tacrolimus. The efficacy of tacrolimus was assessed using MG-activities of daily living (MG-ADL) score, Osserman classification, Myasthenia Gravis Foundation of America (MGFA) post intervention status (PIS), the number of hospitalizations, the number of myasthenic crises and deaths. The adverse drug effects of tacrolimus were monitored., Results: A total of 124 patients were included. The tacrolimus group had a significantly lower MG-ADL score than the control group at follow-up (1.90 ± 2.27vs 2.97 ± 2.78, p = 0.029). The difference of MG-ADL score between baseline and after follow-up was significantly greater in the tacrolimus group than the control group (-7.20 ± 2.95 vs -5.52 ± 2.91, p =  0.003). Fewer patients were hospitalized in the tacrolimus group (p =  0.011). The Osserman classification, MGFA PIS, the number of myasthenic crises and deaths did not differ significantly between the two groups. Nineteen patients in the tacrolimus group had adverse drug reactions, but no severe adverse effects appeared., Conclusion: Our study suggested that tacrolimus could be an effective and safe treatment for Osserman grade III and Osserman grade IV MG patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Glioma is the most common tumor among central nervous system tumors; surgical intervention presents difficulties. This is especially the case for gliomas in so-called "eloquent areas," as surgical resection threatens vital structures adjacent to the tumor. Intraoperative magnetic resonance imaging (iMRI) combined with multimodal neuronavigation may prove beneficial during surgery. This study explored the applicability of 3.0 T high field iMRI combined with multimodal neuronavigation in the resection of gliomas in eloquent brain areas.We reviewed 40 patients with a glioma located in the eloquent brains areas who underwent treatment in the Neurosurgery Department of Peking University International Hospital between December 2015 and August 2017. The experimental group included 20 patients treated using iMRI assistance technology (iMRI group). The remaining 20 patients underwent treatment by conventional neuronavigation (non-iMRI group). Tumor resection degree, preoperative and postoperative ability of daily living scale (Barthel index), infection rate, and operative time were compared between the 2 groups.No difference in infection rate was observed between the 2 groups. However, compared with the non-iMRI group, the iMRI group had a higher resection rate (96.55 ± 4.03% vs 87.70 ± 10.98%, P = .002), postoperative Barthel index (90.75 ± 12.90 vs 9.25 ± 16.41, P = .018), as well as a longer operation time (355.85 ± 61.40 vs 302.45 ± 64.09, P = .011).The use of iMRI technology can achieve a relatively higher resection rate among cases of gliomas in eloquent brain areas, with less incidence of postoperative neurological deficits. Although the operative time using iMRI was longer than that taken to perform conventional navigation surgery, the surgical infection rate in these 2 procedures showed no significant difference.

Gastric cancer (GC) is the most common epithelial malignancy worldwide. Basic transcription factor 3 (BTF3) plays a crucial role in the regulation of various biological processes. We designed experiments to investigate the molecular mechanism underlying the role of BTF3 in GC cell proliferation and metastasis. We confirmed that BTF3 expression was decreased in GC tissues and several GC cell lines. Lentivirus-mediated downregulation of BTF3 reduced cell proliferation, induced S and G2/M cell cycle arrest, and increased apoptosis. Knockdown of BTF3 significantly reduced the expression of Forkhead box M1 (FOXM1). Upregulation of FOXM1 significantly inhibited the decrease in cell proliferation due to BTF3 silencing, S and G2/M cell cycle arrest, and increase in apoptosis. Knockdown of BTF3 decreased Ki-67 and PCNA expression, whereas it increased p27 expression, which was inhibited by upregulation of FOXM1. Knockdown of BTF3 significantly decreased the ability to invade and migrate. Moreover, knockdown of BTF3 increased E-cadherin expression, whereas it decreased N-cadherin and ZEB2 expression, indicating a decrease in epithelial-mesenchymal transition (EMT). Phosphorylation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) was significantly inhibited by knockdown of BTF3. IL-6-stimulated phosphorylation of STAT3 and JAK2 markedly suppressed inhibition of EMT due to BTF3 silencing. Silencing of BTF3 decreased tumor volume and weight and reduced peritoneal nodules in implanted tumors. Our findings provide a novel understanding of the mechanism of GC and highlight the important role of BTF3/FOXM1 in tumor growth and BTF3/JAK2/STAT3 in EMT and metastasis.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography (EDI-OCT) to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging (MRI) findings., Methods: Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First Hospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microbleeds were evaluated. All patients and controls underwent EDI-OCT to measure subfoveal choroidal thickness (SFCT), inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner (AVRin) and outer diameters (AVRout). The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman's correlation was used to investigate the correlation between retinal vessel changes and MRI lesions., Results: In CADASIL patients, mean SFCT (268.37 ± 46.50 μm) and mean arterial inner diameter (93.46 ± 9.70 μm) were significantly lower than that in controls (P < 0.001,P = 0.048, respectively). Mean arterial outer diameter (131.74 ± 10.87 μm), venous inner (128.99 ± 13.62 μm) and outer diameter (164.82 ± 14.77 μm), and mean arterial (19.13 ± 1.85 μm) and venous (17.91 ± 2.76 μm) wall thickness were significantly higher than that in controls (P = 0.023,P = 0.004,P < 0.001,P < 0.001, respectively). Arterial inner diameter (rs= -0.39, P= 0.044), AVRin (rs= -0.65,P < 0.001), and AVRout (rs= -0.56, P= 0.002) showed a negative correlation with the number of small infarcts. Venous inner diameter (rs = 0.46, P= 0.016) showed a positive correlation with the number of small infarcts. Venous inner diameter (rs = 0.59, P= 0.002), outer diameter (rs = 0.47, P= 0.017), showed a positive correlation with the number of cerebral microbleeds (CMBs). AVRin (rs= -0.52, P= 0.007) and AVRout (rs= -0.40, P= 0.048) showed a negative correlation with the number of CMBs., Conclusions: Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might be a useful evaluation tool for CADASIL patients.

The Doppler asymmetric spatial heterodyne (DASH) interferometer provides the capability to retrieve wind speed in the upper atmosphere. The data processing leads to a significant retrieving error with the development of wind precision. The influence of window parameters on the isolated interferogram is analyzed theoretically. Based on the derivation, the system is established, and the interferogram with a small shift is sampled. The phase and wind speed are calculated under various window types and window width values. We conclude that, by choosing the Nuttall window with a small width, the wind retrieving error can be minimized.

This study aimed to investigate the effect of icariin (ICA) on thin endometrium in a rat model. To this end, 6- to 8-week-old female Sprague Dawley rats (105) were randomly divided into 7 groups: untreated, vehicle-treated (lavage with NaCl), high-dose ICA (lavage with ICA at 200 mg∙kg -1 ∙day -1 ), medium-dose ICA (lavage ICA at 100 mg∙kg -1 ∙day -1 ), low-dose ICA (lavage with ICA at 50 mg∙kg -1 ∙day -1 ), sham model (injected with NaCl at uterus horn), and sample group. To induce thin endometrium, rats of all groups (except sham-model) were injected with 95% ethanol via the uterine horn. Each group underwent its respective treatment for 3 estrous cycles, after which 5 rats from each group were sacrificed, and endometrial thickness was measured. The expression of CD31, factor VIII, vascular endothelial growth factor (VEGF), cytokeratin (CK), and vimentin were detected via immunohistochemistry. The results showed that CD31, factor VIII, and VEGF were primarily expressed in the cytoplasm of endometrial and vascular epithelial cells. No difference in the expression of these factors was detected between the ICA lavage groups and the untreated groups. However, high dose ICA-treated group exhibited significantly higher expression of CD31, factor VIII, and VEGF compared to that in the low dose and vehicle-treated groups. CK and vimentin in the endometrial tissue were significantly higher in the untreated and treatment groups compared to the vehicle-treated group. This study demonstrated that ICA increases thickness of the endometrium, and it may modulate expression of VEGF, CD31, and factor VIII.

Competing Interests: There are no conflicts of interest.

Background: Abnormal expression of some CD44 molecules in tumor tissues can induce the degradation of the extracellular matrix, and is closely associated with axillary lymph node metastasis, angiogenesis, cancer progression, and drug resistance., Patients and Methods: We measured and confirmed the expression of CD44st and MMP2 mRNAs and proteins in the cancer tissues and adjacent normal tissues of postoperative non-small cell lung cancer (NSCLC) patients with either adenocarcinoma (n = 72) or squamous cell carcinoma (n = 53) using quantitative reverse transcription polymerase chain reaction, gene sequencing, and immunohistochemical analysis., Results: CD44st and MMP2 expression were closely associated with the histopathological classification, lymph node metastasis, and TNM stage of the tumors, and the difference was statistically significant (p < 0.05). The median overall survival (OS) for the high CD44st expression group was 30.52 months (95% confidence interval (CI) 24.02-36.15); for the low expression group it was 43.23 months (95% CI 31.81-52.02) (p = 0.020). The median OS for the high MMP-2 expression group was 30.53 months (95% CI 26.69-33.31); for the low expression group it was 40.06 months (95% CI 33.55-46.45) (p = 0.022)., Conclusion: The rates of CD44st and MMP2 expression were higher in squamous cell carcinomas than in adenocarcinomas, were closely associated with lymph node metastasis and TNM stage, and affected patients' prognoses., (© 2017 S. Karger GmbH, Freiburg.)

Spatial heterodyne Raman spectroscopy (SHRS) is a new type of Raman spectroscopic detection technique with characteristics of high optical throughout, high spectral resolution, and no moving parts. SHRS is very suitable for the planetary exploration missions, which can be used to the analysis of minerals and find the biomarkers maybe exist on the surface of planetary. The authors have applied the technique to the standoff Raman spectroscopic detection, analyzed the main characteristics, including spectral resolution, bandpass and signal to noise (SNR), of standoff SHRS and proved it through experiments. The basic theory of standoff SHRS has been described briefly while a breadboard has been designed, built and calibrated. On the basis, the Raman spectra of some inorganic solids, organic liquids and some natural minerals have been achieved at a distance of 10 m, the SNR of the breadboard has been estimated. Due to the poor adjustment and the defects of the optical elements, the breadboard is far away from an ideal system. But the results show that the SNR is better than 5 for most of the main Raman peaks of the samples, which can meet the basic requirement of clear positive detection of typical Raman peaks and the feasibility of standoff SHRS has been proved. SHRS can overcome the main defects of dispersive grating Raman spectrometers and Fourier transform Raman spectrometers and it has a great application prospect on the detection and analysis of the planetary surface. The work of the authors can prove the potentiality of SHRS on standoff detection and can provide reference for the engineering realization of standoff SHRS.

Objectives: The management of non-small cell lung cancer (NSCLC) relies on the tumour-node-metastasis (TNM) stage, and the treatment regimen differs based on the N status. Positron emission tomography-computed tomography (PET-CT) has emerged as a powerful imaging tool for the detection of various cancers with a relatively low false-negative rate. We explored predictors to identify false-negative N2 disease in PET-CT., Methods: A total of 284 consecutive cN0 patients with peripheral NSCLC who underwent PET-CT scans followed by curative intent resections were enrolled as a training set to identify predictors of occult N2 metastases by multivariable analysis. The accuracy and cut-off values for the predictors were calculated using a receiver operating characteristic curve. Clinical and pathological data were analysed retrospectively. An additional 151 patients were collected as a test set to validate the results, including the occult N2 rate and accuracy., Results: In total, 8.5% (24/284) PET-CT-diagnosed N0 NSCLC cases had pathologically diagnosed N2 metastases. The SUV max of the primary tumour was a unique independent risk factor for occult N2 NSCLC [P = 0.003, 95% confidence interval = 0.81-0.96, odds ratio (OR) = 0.88]. Occult N2 metastases occurred more frequently in the subcarinal (16/24) and right lower paratracheal lymph nodes (12/24). Accordingly, we divided the patients into two groups by SUV max : the occult N2 rates in the SUV max of <2.6 and SUV max of ≥2.6 groups were 1.0% (1/100) and 12.5% (23/184), respectively (P = 0.001). In the test set, the occult N2 incidence rate was 9.3% (14/151), with the highest rates occurring in the subcarinal (9/14) and right lower paratracheal lymph nodes (6/14). In the two groups defined by SUV max , the occult N2 rates were 4% (2/50) and 11.9% (12/101), respectively., Conclusions: The SUV max of the primary tumour was an independent risk factor for occult N2 metastases in NSCLC patients diagnosed as clinical N0 by PET-CT. SUV max of ≥2.6 of the primary tumour may indicate the risk of N2 metastases, and invasive mediastinal staging techniques or comprehensive therapy should not be ignored in these patients., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: MicroRNAs are believed to influence breast cancer cell tumorgenicity by interacting with the production of tumor associated macrophages. At this stage, this hypothesis lacks sufficient empirical evidence. Our study is an investigation of the effects of let-7a on the function of human breast cancer cell lines that had undergone chemokine ligand 18 (CCL18) stimulation., Methods: Two breast cancer cell lines MDA-MB-231 and MCF-7 were transfected with let-7a mimics with or without CCL18 simulation. The expression level of let-7a was evaluated with qRT-PCR. Our study examined cell proliferation, migration and cell cycles following let-7a treatment. The predicted target of let-7a was identified and confirmed in vitro by a dual luciferase reporter system. The associations between let-7a, CCL18 and target gene expression were evaluated using RT-PCR and the Western blotting method., Results: The downregulated expression level of let-7a was observed in both breast cancer cell lines. When compared to the control and CCL18 stimulation groups, cell proliferation and migration in MDA-MB-231 and MCF-7 cells were significantly inhibited by let-7a. Furthermore, the cell cycle was dramatically blocked at the G2/M phase. The luciferase reporter identified Lin28 as the direct binding target of let-7a in both breast cancer cell lines., Conclusion: Upregulation of let-7a carries the potential to reverse CCL18 induced cell proliferation and migration alteration in breast cancer cells by regulating Lin28 expression. Our results provided evidence which suggests the use of let-7a as a therapeutic agent in the treatment of breast cancer., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Exogenous substance P accelerates wound healing in diabetes, but the mechanism remains poorly understood. Here, we established a rat model by intraperitoneally injecting streptozotocin. Four wounds (1.8 cm diameter) were drilled using a self-made punch onto the back, bilateral to the vertebral column, and then treated using amniotic membrane with epidermal stem cells and/or substance P around and in the middle of the wounds. With the combined treatment the wound-healing rate was 100% at 14 days. With prolonged time, type I collagen content gradually increased, yet type III collagen content gradually diminished. Abundant protein gene product 9.5- and substance P-immunoreactive nerve fibers regenerated. Partial nerve fiber endings extended to the epidermis. The therapeutic effects of combined substance P and epidermal stem cells were better than with amniotic membrane and either factor alone. Our results suggest that the combination of substance P and epidermal stem cells effectively contributes to nerve regeneration and wound healing in diabetic rats.

Objective: Previous studies have shown that the Ginkgo biloba extract (EGb761) can be used to anti-cancer. However, the mechanism by which EGb761 mediate this effect is still unclear. In the present study, EGb761 inhibited cell proliferation and induced cell apoptosis in gastric cancer cell was explored., Methods: The cell viability was detected by the CCK8 assay. The cell cycle and apoptosis was assessed by flow cytometry. The protein expression of caspase-3, p53 and Bcl-2 were analyzed by western blot., Results: Treatment of human gastric cancer cells with EGb761 induced cell death in a dose-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that gastric cancer cells were accumulated in G0/G1 phase when exposed to EGb761. Furthermore, the proportion of apoptosis cells was increased after EGb761 treatment as compared to untreated group. In addition, our results showed that the treatment of AGS cells with EGb761 significantly increased the expression of caspase3 and p53, and decreased the anti-apoptotic Bcl-2 level., Conclusions: Our results demonstrated that EGb761 could inhibit gastric cancer proliferation through adjusting cell cycle and inducing cell apoptosis.

Aim: To determine the value of computed tomographic angiography (CTA) for diagnosis and therapeutic planning in lower gastrointestinal (GI) bleeding., Methods: Sixty-three consecutive patients with acute lower GI bleeding underwent CTA before endovascular or surgical treatment. CTA was used to determine whether the lower GI bleeding was suitable for endovascular treatment, surgical resection, or conservative treatment in each patient. Treatment planning with CTA was compared with actual treatment decisions or endovascular or surgical treatment that had been carried out in each patient based on CTA findings., Results: 64-row CTA detected active extravasation of contrast material in 57 patients and six patients had no demonstrable active bleeding, resulting in an accuracy of 90.5% in the detection of acute GI bleeding (57 of 63). In three of the six patients with no demonstrable active bleeding, active lower GI bleeding recurred within one week after CTA, and angiography revealed acute bleeding. The overall location-based accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the detection of GI bleeding by 64-row CTA were 98.8% (249 of 252), 95.0% (57 of 60), 100% (192 of 192), 100% (57 of 57), and 98.5% (192 of 195), respectively. Treatment planning was correctly established on the basis of 64-row CTA with an accuracy, sensitivity, specificity, PPV and NPV of 98.4% (248 of 252), 93.3% (56 of 60), 100% (192 of 192), 100% (56 of 56), and 97.5% (192 of 196), respectively, in a location-based evaluation., Conclusion: 64-row CTA is safe and effective in making decisions regarding treatment, without performing digital subtraction angiography or surgery, in the majority of patients with lower GI bleeding.

CD44, a major receptor for hyaluronan (HA), is a member of a class of adhesion molecules of unknown classification involved in cell proliferation, differentiation, migration, angiogenesis, and the presentation of specific cytokines to the corresponding receptors as well as in cell signaling transduction. It has recently been discovered that CD44, a marker of tumor stem cells, is involved in the drug resistance and invasion of multiple types of tumors. The 20 exons in the CD44 gene that are alternatively spliced, give rise to many CD44 isoforms, possibly including tumor-specific sequences. Dozens of CD44 isoforms have been found, to date, and the standard CD44 (CD44s) isoform is the most common. We recently showed that a novel short-tail isoform of CD44 (CD44st) was expressed in multidrug-resistant human breast cancer MCF-7/Adr cells. Moreover, the novel CD44st was able to interact with HA and regulate the expression of matrix metalloproteinase (MMP)-2 and MMP-9, which increased the invasive capability of MCF-7 cells through the Ras/MAPK signaling pathway. In the present study, we verified that MCF-7 cells subjected to drug pressure develop multidrug resistance to doxorubicin, and the expression levels of multidrug resistance protein 1 (MDR1), CD44st and nuclear factor-κB (NF-κB) mRNA and protein were gradually upregulated in a dose‑dependent manner in MCF-7 cells treated with doxorubicin. HA increases the secretion of MMP-2 and MMP-9 in multidrug-resistant MCF-7 cells and affected the invasive ability of MCF-7 cells through the upregulation of CD44st expression, and such an effect was blocked by the NF-κB-specific inhibitor BMS-345541.

A new non-specific nuclease from Yersinia enterocolitica subsp. palearctica ( Y. NSN ) was expressed in Escherichia coli ( E. coli ) BL 21 Star TM (DE3)plysS. Induction conditions, including isopropyl-β-D-thiogalactoside (IPTG) concentration, cell density (OD600), induction time and induction temperature, were optimized using response surface methodology. Statistical analysis of the results revealed that induction temperature and all the quadratic terms of variables had significant effects on enzyme activity of Y. NSN . The optimal induction conditions were as follows: 1.5 mmol/L IPTG, OD600 of 0.80, induction time of 20.5 h, and induction temperature of 32 °C. Under the optimized conditions, the highest enzyme activity could be obtained.

Near infrared diffuse reflection spectra of 15 species' 171 samples of Dendrobium combined with chemometrics statistical analysis were used to build prediction model, in order to discriminate different species of Dendrobium quickly and nondestructively. Hotelling T2 was applied to stability analysis of spectrum of 5 random drawing samples, and the results showed that the samples spectrum possessed good stability. Orthogonal test L24 (2 x 4 x 3 x 8) was designed to optimize optical path type, spectral band, derivative and smooth. The result of orthogonal test was analyzed by principal component analysis, which revealed that when 6500-4000 cm(-1) spectral band was applied, and with multiplicative scatter correction, second derivative, Norris smooth, and the number of principal components 7, the spectrum distinguishing accuracy was 100%. With the optimized condition of orthogonal test as the input value of partial least squares discriminant analysis and random drawing 123 samples as calibration set to establish the prediction model, and the rest 48 samples as prediction set were use to assess the property of the prediction model, the results indicated that the accumulating contribution rate of the first 3 principal components of the model was 99.36%, the identification of the standard deviation was +/- 0.1, and the correct recognition rate of the model was 97.92%. The results were satisfied. The method provided a new way for the rapid identification of different species of Dendrobium, and also supplied a reference for the authentication of medicinal plants.

In this paper, the physical and chemical characteristics, biological structure and function of a non-specific nuclease from Yersinia enterocolitica subsp. palearctica (Y. NSN) found in our group were studied using multiple bioinformatics approaches. The results showed that Y. NSN had 283 amino acids, a weight of 30,692.5 ku and a certain hydrophilic property. Y. NSN had a signal peptide, no transmembrane domains and disulphide bonds. Cleavage site in Y. NSN was between pos. 23 and 24. The prediction result of the secondary structure showed Y. NSN was a coil structure-based protein. The ratio of α-helix, β-folded and random coil were 18.73%, 16.96% and 64.31%, respectively. Active sites were pos. 124, 125, 127, 157, 165 and 169. Mg(2+) binding site was pos. 157. Substrate binding sites were pos. 124, 125 and 169. The analysis of multisequencing alignment and phylogenetic tree indicated that Y. NSN shared high similarity with the nuclease from Y. enterocolitica subsp. enterocolitica 8081. The enzyme activity results showed that Y. NSN was a nuclease with good thermostability., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) was encapsulated in alginate-skim milk microspheres. Characteristics of encapsulated L. bulgaricus, such as pH stability, bile stability, storage stability and release property, were studied in this paper. The viability of free L. bulgaricus was not observed after 1 min in simulated gastric fluids (SGF) at pH 2.5 or 2.0. Compared with that of free L. bulgaricus, the viability of encapsulated L. bulgaricus only decreased 0.7 log CFU/g and 2 log CFU/g after 2.0 h incubation in SGF at pH 2.5 and pH 2.0, respectively. L. bulgaricus was also sensitive to bile solution. The viability of free L. bulgaricus was fully lost after 1 h incubation in 1 and 2% bile solution, while the viability of encapsulated L. bulgaricus was only lost 2 log CFU/g and 2.6 log CFU/g in 1 and 2% bile solution at the same time, respectively. Encapsulated L. bulgaricus could be completely released from microspheres in simulated intestinal fluid (pH 6.8) within 2 h. The viability of encapsulated L. bulgaricus retained around 8 log CFU/g when stored at 4°C for 30 days. The current encapsulation technique enables a large proportion of L. bulgaricus to remain good bioactive in a simulated gastrointestinal tract environment.

The aim of this study was to evaluate the association between thymidylate synthase ( TS ), methylenetetrahydrofolate reductase ( MTHFR ) and reduced folate carrier ( SLC19A1) gene polymorphisms and the treatment efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Advanced NSCLC patients received pemetrexed and cisplatin every three weeks. Polymorphisms in the TS , MTHFR and SLC19A1 genes were detected in peripheral blood samples using DNA sequencing and Taqman PCR. An analysis of gene polymorphisms was performed with respect to the progression-free survival (PFS), response rate (RR) and overall survival (OS) of patients treated with pemetrexed. The median PFS times for patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes were significantly longer than those of patients with the 2R/3G, 3C/3G or 3G/3G genotypes (P=0.036). Patients with the SLC19A1 CC genotype had a significantly longer median OS compared with individuals with the homozygous and heterozygous genotypes (12.2 vs. 8.9 and 7.3 months, respectively; P=0.022). The PFS and OS did not differ for the three genotypes of MTHFR assessed. The RR was higher in patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes than in the other groups (P=0.044). The polymorphisms of the 5'-UTR of the TS gene and exon 6 (2522) C/T of the SLC19A1 gene predict the survival of advanced NSCLC patients treated with pemetrexed. However, a large scale clinical trial is required to validate these findings.

Objective: To investigate the feasibility and safety of adult-to-adult living-related donor liver transplantation using a right lobe graft., Methods: The clinical data of 2 cases of living-related donor liver transplantation performed between July, 2010 and November, 2010 were analyzed., Results: Liver transplantation was performed using a right lobe graft including the middle hepatic vein in one case and a right lobe graft without the middle hepatic vein in the other. The ratio of graft volume to standard liver volume was 46.2% and 47.3% in the two cases, with GR/WR of 0.83 and 0.80, and donor residue liver of 42.1% and 39.5%, respectively. The donor operation lasted for 6.5 h and 5 h in the two cases with blood loss of about 200-250 ml without blood transfusion. The donors recovered uneventfully without any surgical complications, whose liver function was normal 7 days after the operation, and were discharged 14 days and 16 days after the surgery, respectively. The recipient operation lasted for 8 h and 7 h with blood loss of about 800-1000 ml. The right hepatic vein, hepatic artery, portal vein and bile duct reconstruction were performed by end-to-end anastomoses in the 2 recipients. Bile duct anastomosis stricture occurred in the first recipient 2 months after transplantation and was treated with percutaneous transhepatic cholangiography and drainage. The second recipient recovered smoothly without any complications. The recipients have so far survived 9 months and 5 months, respectively., Conclusion: Adult-to-adult living-related donor liver transplantation is a safe and effective option for treatment of end-stage liver diseases in the context of cadaveric liver graft shortage.

Objective: To explore the expression and clinical significance of LI (liver-intestine)-cadherin mRNA and protein expression level in hepatocellular carcinoma., Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical techniques were used to detect the expression of the LI-cadherin mRNA and protein in 56 cases of hepatocellular carcinoma, 44 cases of corresponding paracancerous tissues and 9 cases of normal liver tissues. The relationships with its clinicopathological characteristics were analyzed., Results: The mRNA of LI-cadherin was expressed in 56 cases of hepatocellular carcinoma tissues and 44 cases of corresponding paracancerous tissues. But its expression was not detected in normal tissues. Semiquantitative analysis showed that the mRNA expression level of LI-caherin was greater in hepatocellular carcinoma tissues than that in corresponding paracancerous tissues (0.653 ± 0.147 vs 0.534 ± 0.138). The differences were statistically significant (P < 0.01). The positive rates of LI-cadherin protein were 64.29% (36/56) in hepatocellular carcinoma tissues, 22.73% (10/44) in paracancerous tissues and 0% (0/9) in normal tissues., Conclusion: The expression of LI-cadherin is up-regulated significantly in HCC. The over-expression of LI-cadherin protein is correlated with the lymph node metastasis and tumor thrombi in portal vein. It indicates that LI-cadherin may play an important role in the progression and metastasis of HCC.

The culture conditions in CO(2) fixation by Actinobacillus succinogenes for succinic acid production were investigated by a model of available CO(2) in a 3-l fermentor. The results from the model analysis showed that the available CO(2) for succinic acid production in the fermentation broth is the sum of HCO(3) (-), CO(3) (2-), and CO(2) influenced by external culture conditions such as medium components, CO(2) partial pressures, and temperature. The optimized conditions for CO(2) supply in a 3-l fermentor were determined as follows: CO(2) partial pressure and stirring speed were maintained at 0.1 MPa and 200 r min(-1), respectively, with a pH of 6.8 and a temperature of 37°C; 0.15 mol l(-1) NaHCO(3) was added. Under the optimized conditions, a CO(2) fixation rate of 0.57 g l(-1) h(-1) was obtained, and a succinic acid concentration of 51.6 g l(-1) with a yield of 75.8% was reached. These results suggest that optimized conditions of CO(2) supply are effective in high succinic acid production and thus have potential applications in succinic acid production and CO(2) fixation.

Background: CD44, a hyaluronan (HA) receptor, is a multistructural and multifunctional cell surface molecule involved in cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, chemokines and growth factors to the corresponding receptors, and docking of proteases at the cell membrane, as well as in signaling for cell survival. The CD44 gene contains 20 exons that are alternatively spliced, giving rise to many CD44 isoforms, perhaps including tumor-specific sequences., Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to detect CD44st mRNA and CD44 protein in sensitive MCF-7, Lovo, K562 and HL-60 cell lines as well as their parental counterparts, respectively. The full length cDNA encoding CD44st was obtained from the total RNA isolated from MCF-7/Adr cells by RT-PCR, and subcloned into the pMD19-T vector. The CD44st gene sequence and open reading frame were confirmed by restriction enzyme analysis and nucleotide sequencing, and then inserted into the eukaryotic expression vector pcDNA3.1. The pcDNA3.1-CD44st was transfected into MCF-7 cells using Lipofectamine. After transfection, the positive clones were obtained by G418 screening. The changes of the MMP-2 and MMP-9 genes and protein levels were detected by RT-PCR and gelatin zymography, respectively. The number of the cells penetrating through the artificial matrix membrane in each group (MCF-7, MCF-7+HA, MCF-7/neo, MCF-7/neo+HA, MCF-7/CD44st, MCF-7/CD44st+HA and MCF-7/CD44st+Anti-CD44+HA) was counted to compare the change of the invasion capability regulated by the CD44st. Erk and P-Erk were investigated by Western blotting to approach the molecular mechanisms of MMP-2 and MMP-9 expression regulated by the CD44st., Results: Sensitive MCF-7, Lovo, K562 and HL-60 cells did not contain CD44st mRNA and CD44 protein. In contrast, the multidrug resistance MCF-7/Adr, Lovo/Adr, K562/Adr and HL-60/Adr cells expressed CD44st mRNA and CD44 protein. The CD44st mRNA gene sequence was successfully cloned into the recombinant vector pcDNA3.1 and identified by the two restriction enzymes. It was confirmed that the reconstructed plasmid contained the gene sequence of CD44st that was composed of exons 1 to 4, 16 to 17, and 1 to 205 bases of exons 18. The new gene sequence was sent to NCBI for publication, and obtained the registration number FJ216964. The up-regulated level of the mRNA of the CD44 gene and the CD44 protein were detected, respectively, by RT-PCR and flow cytometry in MCF-7 cells transfected with pcDNA3.1-CD44st. The invasiveness of the cells and the activity of MMP-2 and MMP-9 were clearly activated by HA treatment, and blocked by CD44 neutralizing antibody. MCF-7/CD44st cells pretreated with the neutralizing antibody against CD44, and the inhibitor of MAPKs signaling pathway, could strongly block the expression of P-Erk., Conclusions: A new CD44st was expressed in multidrug resistant MCF-7/Adr, Lovo/Adr, K562/Adr and HL-60/Adr cells. The expression vector pcDNA3.1-CD44st was cloned and constructed successfully, and stably transfected into MCF-7 cells. HA could interact with the new CD44st and regulate the expression of MMP-2 and MMP-9, which could increase the invasion capability of MCF-7 cells through the Ras/MAPK signaling pathway.

An industrial fermentation system using lignocellulosic hydrolysate, waste yeast hydrolysate, and mixed alkali to achieve high-yield, economical succinic acid production by Actinobacillus succinogenes was developed. Lignocellulosic hydrolysate and waste yeast hydrolysate were used efficiently as carbon sources and nitrogen source instead of the expensive glucose and yeast extract. Moreover, as a novel method for regulating pH mixed alkalis (Mg(OH)(2) and NaOH) were first used to replace the expensive MgCO(3) for succinic acid production. Using the three aforementioned substitutions, the total fermentation cost decreased by 55.9%, and 56.4 g/L succinic acid with yield of 0.73 g/g was obtained, which are almost the same production level as fermentation with glucose, yeast extract and MgCO(3). Therefore, the cheap carbon and nitrogen sources, as well as the mixed alkaline neutralize could be efficiently used instead of expensive composition for industrial succinic acid production., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate whether the growth, apoptosis and sensitivity to anticancer agent could be altered after introduction of YB-1 shRNA eukaryotic expression vector into the K562/A02 cells, and its possible molecular mechanisms. The recombinant eukaryotic expression plasmids including YB-1 shRNA and the vector-random-sequence were introduced into K562/A02 cells by lipofectamine mediation, and the positive clones were screened by G418. RT-PCR and Western blot were employed to detect the expression of mRNA and protein of YB-1 in leukemia cells, respectively. The proliferative ability of the cells was determined by MTT assay and cell cycle analysis. Apoptosis of K562/A02 cells was assayed by AnnexinV-FITC/PI double labeled flow cytometry. The drug sensitivity to anticancer agent was determined by MTT assay. The expressions of MDR1 gene and P-gp were detected by RT-PCR and flow cytometry respectively. The results indicated that the levels of mRNA and protein of YB-1 decreased dramatically in three groups of positively transfected cells when compared with control cells. The inhibitory rates of 3 different shRNA sequences targeting YB-1 gene were (65.1 ± 2.1)%, (27.4 ± 1.3)% and (67.4 ± 1.6)% respectively. The introduction of exogenous YB-1 shRNA gene into K562/A02 cells resulted in decreased levels of the proliferative ability in K562/A02 cells, and displayed higher at G(1), lower at G(2) and S phase in cell cycle distribution in comparison with the control groups. AnnexinV/PI detection indicated higher AnnexinV(+) ratio in 3 groups of positively transfected cells after being treated with As(2)O(3) of 0.5 µmol/L for 24 hours. The IC(50) values of doxorubicin in 3 groups of positively transfected cells were significantly lower than that in control group. The level of MDR1 gene and P-gp decreased significantly in 3 groups of positively transfected cells. It is concluded that the transfection with YB-1 shRNA gene can inhibit the proliferation of leukemia cells and induce cell apoptosis. The expression of MDR1 mRNA and P-gp decrease after transfection of YB-1 shRNA into K562/A02 cells.