Casticin inhibits migration and invasion of hepatocellular carcinoma MHCC97H cells through miR-148a-3p/Wnt1 signaling pathway / 中国药理学通报

Aim To investigate the effect of casticin (CAS) on the migration and invasion of MHCC97H cells and preliminarily explore the molecular mechanism. Methods CCK-8 kit was used to detect the effect of different concentrations of CAS on the viability of MHCC97H cells; cell migration and invasion assays were carried out in groups to assess the migration and invasion ability of MHCC97H cells; reverse transcription fluorescence quantitative PCR (RT-qPCR) was performed to detect the miR-148a-3p and Wnt1 mRNA expression in MHCC97H cells after CAS treatment; migration-invasion related proteins (MMP2, MMP9) and Wnt1 protein expression were detected by Western blot; Dual-Luciferase reporter gene was used to detect the binding of miR-148a-3p to Wnt1 3′-UTR. Results CAS significantly inhibited the viability of MHCC97H cells. The IC

UB-612, a Multitope Universal Vaccine Eliciting a Balanced B and T Cell Immunity against SARS-CoV-2 Variants of Concern

ImportanceThe SARS-CoV-2 non-spike structural proteins of nucleocapsid (N), membrane (M) and envelope (E) are critical in the host cell interferon response and memory T-cell immunity and have been grossly overlooked in the development of COVID vaccines. ObjectiveTo determine the safety and immunogenicity of UB-612, a multitope vaccine containing S1-RBD-sFc protein and rationally-designed promiscuous peptides representing sequence-conserved Th and CTL epitopes on the Sarbecovirus nucleocapsid (N), membrane (M) and spike (S2) proteins. Design, setting and participantsUB-612 booster vaccination was conducted in Taiwan. A UB-612 booster dose was administered 6-8 months post-2nd dose in 1,478 vaccinees from 3,844 healthy participants (aged 18-85 years) who completed a prior placebo (saline)-controlled, randomized, observer-blind, multi-center Phase-2 primary 2-dose series (100-g per dose; 28-day apart) of UB-612. The interim safety and immunogenicity were evaluated until 14 days post-booster. ExposureVaccination with a booster 3rd-dose (100-g) of UB-612 vaccine. Main outcomes and measuresSolicited local and systemic AEs were recorded for seven days in the e-diaries of study participants, while skin allergic reactions were recorded for fourteen days. The primary immunogenicity endpoints included viral-neutralizing antibodies against live SARS-CoV-2 wild-type (WT, Wuhan strain) and live Delta variant (VNT50), and against pseudovirus WT and Omicron variant (pVNT50). The secondary immunogenicity endpoints included anti-S1-RBD IgG antibody, S1-RBD:ACE2 binding inhibition, and T-cell responses by ELISpot and Intracellular Staining. ResultsNo post-booster vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. The UB-612 booster prompted a striking upsurge of neutralizing antibodies against live WT Wuhan strain (VNT50, 1,711) associated with unusually high cross-neutralization against Delta variant (VNT50, 1,282); and similarly with a strong effect against pseudovirus WT (pVNT50, 6,245) and Omicron variant (pVNT50, 1,196). Upon boosting, the lower VNT50 and pVNT50 titers of the elderly in the primary series were uplifted to the same levels as those of the young adults. The UB-612 also induced robust, durable VoC antigen-specific Th1-oriented (IFN-{gamma}+-) responses along with CD8+ T-cell (CD107a+-Granzyme B+) cytotoxicity. Conclusions and relevanceWith a pronounced cross-reactive booster effect on B- and T-cell immunity, UB-612 may serve as a universal vaccine booster for comprehensive immunity enhancement against emergent VoCs. Trial registration[ClinicalTrials.gov: NCT04773067] KEY POINTSO_ST_ABSQuestionC_ST_ABSFacing ever-emergent SARS-CoV-2 variants and long-haul COVID, can composition-updated new vaccines be constructed capable of inducing striking, durable booster-recalled B/T-immunity to prevent infection by VoCs? FindingsIn a Phase-2 extension study, a booster dose of UB-612 multitope protein-peptide vaccine prompted high viral-neutralizing titers against live wild-type virus (VNT50, 1,711), Delta variant (VNT50, 1,282); pseudovirus wild-type (pVNT50, 6,245) and Omicron variant (pVNT50, 1,196). Robust, durable Th1-IFN{gamma}+ responses and CD8+ T cell-(CD107a+-Granzyme B+) cytotoxic activity were both observed. MeaningUB-612 RBD-sFc vaccine armed with T cell immunity-promoting conserved N, M and S2 Th/CTL epitope peptides may serve as a universal vaccine to fend off new VoCs.

Protective Mechanism of Danggui Shaoyaosan on Podocytes of Nephrotic Syndrome Rats Based on AngⅡ-TRPC6 Pathway / 中国实验方剂学杂志

Objective:To explore the protective effect and the mechanism of Danggui Shaoyaosan（DSS） on angiotensin Ⅱ （AngⅡ）/transient receptor potential cation channel 6 （TRPC6） pathway in nephrotic syndrome （NS） rats. Method:In animal experiments， doxorubicin （4 mg·kg^-1 for the 1^st week and 2 mg·kg^-1 for the 2^nd week） was injected twice to the tail vein of rats to induce NS model in 160 rats， which were then randomly divided into model group （normal saline）， losartan group （30 mg·kg^-1·d^-1）， and low-（4.3 g·kg^-1·d^-1）， medium-（8.6 g·kg^-1·d^-1）， and high-dose （17.2 g·kg^-1·d^-1） DSS groups. Besides， a normal group was also set. After intervention for four weeks， ultrastructure changes of the kidney were identified by transmission electron microscopy （TEM）. The 24-hour urine protein was detected by kits. Radioimmunoassay was used to detect the content of AngⅡ and Calcineurin （CaN） in plasma. Western blot was used to detect the protein expression of TRPC6， angiotensin Ⅱ type 1 receptor （AT1R）， podocyte slit diaphragm-specific protein （Nephrin）， and cysteine-aspartic acid protease-3 （Caspase-3） in the renal cortex. Immunohistochemistry was used to detect the expression of TRPC6 and AT1R in the slit diaphragm. In cell experiments， AngⅡ stimulated MPC5 podocytes. The cells were randomly divided into a normal group， an AngⅡ group， an AngⅡ+SAR7334 （TRPC6-specific inhibitor） group， an AngⅡ+5%DSS group， an AngⅡ+10%DSS group， and an AngⅡ+15%DSS group. Western blot was used to detect the protein expression of TRPC6， AT1R， Nephrin， and Caspase-3 in podocytes. Result:Compared with the normal group， the model group showed increased 24-hour urine protein content （<italic>P</italic><0.01） and AngⅡ and CaN in plasma （<italic>P</italic><0.01）， incomplete glomerular structure， the extensive fusion of podocyte process with elevated fusion rate （<italic>P</italic><0.01）， increased expression distribution of AT1R and TRPC6 in the renal cortex， and up-regulated protein expression of AT1R， TRPC6， and Caspase-3 in renal tissues （<italic>P</italic><0.01）， and reduced Nephrin protein expression （<italic>P</italic><0.01）. Compared with model group， the losartan group and the high-dose DSS group exhibited decreased 24-hour urine protein content （<italic>P</italic><0.01） and the content of AngⅡ and CaN in plasma （<italic>P</italic><0.01）， improved glomerular structure， reduced fusion rate of podocyte process （<italic>P</italic><0.01）， diminished expression distribution of TRPC6 and AT1R in the renal cortex， declining protein expression of AT1R， TRPC6 and Caspase-3 in renal tissues （<italic>P</italic><0.01）， and elevated Nephrin protein expression （<italic>P</italic><0.01）. Additionally， compared with the normal podocytes， AngⅡ-stimulated podocytes showed increased protein expression of AT1R， TRPC6 and Caspase-3 （<italic>P</italic><0.01）， and decreased expression of Nephrin （<italic>P</italic><0.01）. Compared with the AngⅡ group， the AngⅡ+SAR7334 group displayed reduced protein expression of AT1R， TRPC6， and Caspase-3 （<italic>P</italic><0.01） and increased protein expression of Nephrin （<italic>P</italic><0.01）. Conclusion:DSS can improve the pathological characteristics of NS presumedly by inhibiting the interaction between AngⅡ and TRPC6 in podocytes and improving the structural integrity of podocytes to repair the damage of glomerular molecular barrier and slow down the progression of NS-induced proteinuria.

A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model

A novel multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and disease is described in this report. The initial development and characterization experiments are presented along with proof-of-concept studies for the vaccine candidate UB-612. UB-612 consists of eight components rationally designed for induction of potently neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist at low concentration as an excipient, and aluminum phosphate adjuvant. Through immunogenicity studies in Guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provides excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses. In challenge studies, UB- 612 vaccination reduced viral load and prevented development of disease in mouse and non-human primate challenge models. With a Phase 1 trial completed, a Phase 2 trial ongoing in Taiwan, and additional trials planned to support global authorizations, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 infection and COVID-19 disease. Author SummarySARS-CoV-2 virus, the causative agent of Coronavirus Disease 2019 (COVID-19), has spread globally since its origin in 2019, causing an unprecedented public health crisis that has resulted in greater than 4.7 million deaths worldwide. Many vaccines are under development to limit disease spread and reduce the number of cases, but additional candidates that promote a robust immune response are needed. Here, we describe a multitope protein-peptide vaccine platform that is unique among COVID-19 vaccines. The advantages of our approach are induction of both high levels of neutralizing antibodies as well as a Th/CTL response in the vaccinated host, which mimics the immune response that occurs after natural infection with SARS-CoV-2. We demonstrate that our vaccine is immunogenic and effective in preventing disease in several animal models, including AAV- hACE-2 transduced mice, and both rhesus and cynomolgus macaques. Importantly, no immunopathology was observed in the lungs of immunized animals, therefore showing that antibody-dependent enhancement (ADE) does not occur. Our study provides an additional, novel vaccine candidate for advancement in clinical trials to treat and prevent SARS-CoV-2 infection and COVID-19 disease.

Is there a primitive reflex residue underlying Marcus Gunn Syndrome? Rat electrophysiology.

AIM: To make an electrophysiological demonstration of a possible jaw muscle afferents-oculomotor neural pathway that was proposed by our previous works on rats, which substantiates an early "release hypothesis" on pathogenesis of human Marcus Gunn Syndrome (MGS). METHODS: Extracellular unit discharge recording was applied and both orthodromic and spontaneous unitary firing were recorded in the oculomotor nucleus (III), and the complex of pre-oculomotor interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN), following electric stimulation of the ipsilateral masseter nerve (MN) in rats. RESULTS: Extracellular orthodromic unit discharges, with latencies of 3.7±1.3 and 4.7±2.9ms, were recorded unilaterally in the III, and the INC/DN neurons, respectively. Spontaneous unit discharges were also recorded mostly in the INC/DN and less frequently in the III. Train stimulation could prompt either facilitation or inhibition on those spontaneous unit discharges. The inhibition pattern of train stimulation on the spontaneous discharging was rather different in the III and INC/DN. A slow inhibitory pattern in which spontaneous firing rate decreased further and further following repeated train stimulation was observed in the III. While, some high spontaneous firing rate units, responding promptly to the train stimuli with a short-term inhibition and recovered quickly when stimuli are off, were recorded in the INC/DN. However, orthodromic unit discharge was not recorded in the III and INC/DN in a considerable number of experiment animals. CONCLUSION: A residual neuronal circuit might exist in mammals for the primitive jaw-eyelid reflex observed in amphibians, which might not be well-developed in all experimental mammals in current study. Nonetheless, this pathway can be still considered as a neuroanatomic substrate for development of MGS in some cases among all MGS with different kind of etiology.

Four new species of Estheria Robineau-Desvoidy (Diptera: Tachinidae) from China and Nepal, with a review of the East Palearctic and Oriental species.

The species of Estheria Robineau-Desvoidy (Diptera: Tachinidae) from the East Palearctic and Oriental regions are reviewed. Eighteen species are recognized: the fourteen previously described, E. acuta (Portschinsky, 1881), E. alticola Mesnil, 1967, E. bucharensis (Kolomiets, 1974), E. cinerella Mesnil, 1967, E. cristata (Meigen, 1826), E. decolor (Pandellé, 1896), E. flavipennis Herting, 1968, E. lacteipennis Mesnil, 1967, E. maculipennis Herting, 1968, E. magna (Baranov, 1935), E. nigripes (Villeneuve, 1920), E. pallicornis (Loew, 1873), E. petiolata (Bonsdorff, 1866) and E. picta (Meigen, 1826), and four species described as new to science, E. hirtinerva Zhang Shima sp. nov. (W China, Nepal), E. prostata Zhang Shima sp. nov. (W China, Nepal), E. tibetensis Zhang Shima sp. nov. (W China, Nepal) and E. wangi Zhang Liang sp. nov. (W China, Pakistan). Estheria acuta and E. decolor are newly recorded for China, E. magna is newly recorded for Malaysia, Pakistan and Vietnam, and E. pallicornis is newly recorded for Nepal. An identification key to the 18 species of Estheria so far known from the East Palearctic and Oriental regions is included, together with 126 figures of heads and habitus of males and females, and male terminalia and known distributions.

Expressions of TGF-β1 and EⅢA-FN after Rat Skeletal Muscle Contusion and Wound Age Estimation / 法医学杂志

Objective To study the expressions of transforming growth factor-β1 （TGF-β1） and EⅢA-fibronectin （EⅢA-FN） at different time points of antemortem injury, antemortem injury postmortem expression and postmortem injury and to explore their application value in wound age estimation. Methods A model of rat skeletal muscle contusion was established. The rats were randomly divided into normal control group （n=5）, antemortem contusion group （n=40）, antemortem contusion postmortem expression group （n=110） and postmortem injury group （n=25）. The expressions of TGF-β1 and EⅢA-FN after rat skeletal muscles antemortem contusion were detected with immunohistochemical staining. Expression changes of TGF-β1 and EⅢA-FN mRNA in each group were analyzed with real-time fluorescence quantitative PCR. Results Immunohistochemical staining results showed that a large number of polymorphonuclear leukocyte, mononuclear cells and fibroblastic cells showed a strong expression of TGF-β1 in wounded zones 12 h-14 d after antemortem contusion. EⅢA-FN was mainly distributed in the extracellular matrix, 3 to 7 d post-traumatic. Real-time fluorescence quantitative PCR results showed that TGF-β1 and EⅢA-FN mRNA in antemortem injury group reached the peak at 3 and 5 d post-traumatic respectively. The expressions of TGF-β1 and EⅢA-FN mRNA in antemortem contusion postmortem expression group peaked at 6 h and 12 h postmortem. The expression of TGF-β1 and EⅢA-FN mRNA in postmortem injury group 0.5-12 h postmortem was significantly lower than those of the normal control group and the antemortem contusion group. Conclusion TGF-β1 and EⅢA-FN might become a reference index for skeletal muscle wound age estimation.

Is Marcus Gunn jaw winking a primitive reflex? Rat neuroanatomy.

AIM: To investigate a possible trigeminal proprioceptive-oculomotor neural pathway and explore possible synaptic connections between neurons in this pathway. Attempt to bring a new insight to mechanism of Marcus Gunn syndrome (MGS). METHODS: Anterograde and retrograde tract tracing was applied and combined with immunofluorescent stain in rats. After electrophysiological identifying mesencephalic trigeminal nucleus (Vme) neurons, intracellular injection of tracer was performed to trace axon trajectory. RESULTS: Following injections of anterograde tracers into the Vme, labeled terminals were observed ipsilateral in oculomotor and trochlear nuclei (III/IV), as well as in their premotor neurons in interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN). Combining with choline acetyltransferase (ChAT) immunofluorescent stain, it showed that Vme projecting terminals contact upon ChAT positive III/IV motoneurons under confocal microscope. By retrograde labeling premotor neurons of the III, it showed that Vme neuronal terminals contact with retrogradely labeled pre-oculomotor neurons in the INC/DN. Axons of intracellularly labeled Vme neurons that respond to electric stimuli of the masseter nerve traveled into the ipsilateral III. CONCLUSION: There may exist a trigeminal proprioceptive-oculomotor system neural circuit in the rat, which is probably related to vertical-torsional eye movements. Possible association of this pathway with MGS etiology was discussed.

Microglia activation mediated by toll-like receptor-4 impairs brain white matter tracts in rats.

Microglia activation and white matter injury coexist after repeated episodes of mild brain trauma and ischemic stroke. Axon degeneration and demyelination can activate microglia; however, it is unclear whether early microglia activation can impair the function of white matter tracts and lead to injury. Rat corpus callosum (CC) slices were treated with lipopolysaccharide (LPS) or LPS + Rhodobacter sphaeroides (RS)-LPS that is a toll-like receptor 4 (TLR-4) antagonist. Functional changes reflected by the change of axon compound action potentials (CAPs) and the accumulation of ß-amyloid precursor protein (ß-APP) in CC nerve fibers. Microglia activation was monitored by ionized calcium binding adaptor-1 immunofluorescent stain, based on well-established morphological criteria and paralleled proportional area measurement. Input-output (I/O) curves of CAPs in response to increased stimuli were significantly downshifted in a dose-dependent manner in LPS (0.2, 0.5 and 1.0 µg/mL)-treated slices, implying that axons neurophysiological function was undermined. LPS caused significant ß-APP accumulation in CC tissues, reflecting the deterioration of fast axon transport. LPS-induced I/O curve downshift and ß-APP accumulation were significantly reversed by the pre-treatment or co-incubation with RS-LPS. RS-LPS alone did not change the I/O curve. The degree of malfunction was correlated with microglia activation, as was shown by the measurements of proportional areas. Function of CC nerve fibers was evidently impaired by microglia activation and reversed by a TLP-4 antagonist, suggesting that the TLP-4 pathway lead to microglia activation.

Effect of temperature on content of baicalin and expression of key enzyme genes in callus of Scutellaria baicalensis / 中国中药杂志

The study is aimed to explore the effect of different temperature on the content of baicalin and gene expression in the growth of Scutellaria baicalensis. Four culture temperatures were used to establish the callus culture of S. baicalensis under dark conditions for 40 days and once every 5 days. The growth and baicalin contents were determined. 18S RNA was used as a reference gene to analyze the five key factors in baicalin biosynthesis pathway (PAL), cinnamic acid 4-hydroxylase (C4H), chalcone synthase (CHS), β-glucuronidase (GUS), baicalein-7--glucuronosyltransferase (UBGAT) gene expression levels. The results showed that biomass, baicalin content and accumulation increased with the increase of temperature. 25 °C and 30 °C were more suitable for the growth of S. baicalensis. The content and accumulation of baicalin at 25 °C reached the highest level at 30 days, reaching 2.75% and 12.44 mg, respectively. The relative expression levels of C4H, CHS, GUS and UGBAT genes at 15 °C were higher than those at other treatments. The correlation between the relative expression levels of each key enzyme and the content of baicalin was negatively correlated with the increase of incubation temperature. The relative expression levels of PAL, C4H and CHS genes at 25 °C and 30 °C were significantly correlated with the contents of baicalin and reached a highly significant or significant level. Relative low temperature conditions were not conducive to the growth of S. baicalensis and the accumulation of baicalin. The accumulation of baicalin by PAL and C4H in the upstream of the synthetic pathway was significant.

Safety and effectiveness of drug-eluting stent versus coronary artery bypass grafting for left anterior descending coronary artery stenosis: a systematic review / 军事医学

Objective To systematically review the efficacy and safety of drug-eluting stent(DES) versus coronary artery bypass grafting(CABG) in the treatment of left anterior descending coronary artery(CAD) stenosis.Methods Literature about the efficacy and safety of DES versus CABG for LAD stenosis was retrieved from digital databases of MEDLINE, EMbase, PubMed, and the Cochrane Library by November 2016.Data extraction and quality assessment of included studies were conducted by two independent reviewers.RevMan 5.3 software was used to perform meta-analysis.Results Ten studies involving 9771 patients were finally included.The results of meta-analysis showed that there was no significant difference in mortality [RR=0.88,95%CI(0.70,1.11),P=0.28],major adverse cardiovascular events[MACE,RR=1.04,95%CI(0.88,1.24),P=0.63] or myocardial infarction [MI,RR=0.92,95%CI(0.56,1.53),P=0.75], but PCI-DES significantly increased the risk of TVR [OR=2.43,95%CI(1.61,3.69),P<0.0001].Conclusion For LAD stenosis, PCI-DES strategy causes as high a rate of mortality, MACE and MI as CABG or DES, but PCI-DES can significantly increase the risk of TVR, so we should be cautious clinically.

Relationship between narcissism and entrepreneurial intention in college students / 中国心理卫生杂志

Objective:To investigate the relationship between narcissism and entrepreneurial intention and roles of achievement motive and risk aversion in college students.Methods:In this study,375 college students were selected from Henan University.Their narcissism,entrepreneurial intention,achievement motive and risk aversion were assessed with the Narcissism Scale,Entrepreneurial Intentions,The Achievement Motive Scale,and General Risk Aversion Scale.Results:The scores of overt narcissism positively predicted the scores of entrepreneurial intention (3 =0.37,P ＜ 0.001),the predictive effect of covert narcissism on entrepreneurial intention was not significant (β =-0.05,P ＞ 0.05).The scores of achievement motive partly mediated the relationship between the scores of overt narcissism and entrepreneurial intention (95％ CI:0.06-0.22),and this mediation effect was moderated by the scores of risk aversion (β =0.09,P ＜ 0.05).Only when the score of risk aversion was higher (above one standard deviation),achievement motive was a mediator between narcissism and entrepreneurial intention.When the score of risk aversion was lower,the mediate effect was not valid.Therefore,the moderated mediation model was confirmed.Conclusion:It suggest that the moderated mediation model is feasible,that is,achievement motive is a mediator between narcissism and entrepreneurial intention,but this mediation is moderated by risk aversion.

EZH2 promotes colorectal cancer stem-like cell expansion by activating p21cip1-Wnt/ß-catenin signaling.

Because colorectal cancer (CRC) stem-like cells (CCS-like cells) contribute to poor patient prognosis, these cells are a potential target for CRC therapy. However, the mechanism underlying the maintenance of CCS-like cell properties remains unclear. Here, we found that patients with advanced stage CRC expressed high levels of polycomb group protein enhancer of zeste homologue 2 (EZH2). High expression of EZH2 in tumor tissues correlated with poor patient prognosis. Conversely, silencing EZH2 reduced CRC cell proliferation. Surprisingly, EZH2 was more highly expressed in the CCS-like cell subpopulation than in the non-CCS-like cell subpopulation. EZH2 knockdown significantly reduced the CD133+/CD44+ subpopulation, suppressed mammosphere formation, and decreased the expression of self-renewal-related genes and strongly impaired tumor-initiating capacity in a re-implantation mouse model. Gene expression data from 433 human CRC specimens from TCGA database and in vitro results revealed that EZH2 helped maintain CCS-like cell properties by activating the Wnt/ß-catenin pathway. We further revealed that p21cip1-mediated arrest of the cell cycle at G1/S phase is required for EZH2 activation of the Wnt/ß-catenin pathway. Moreover, the specific EZH2 inhibitor EPZ-6438, a clinical trial drug, prevented CRC progression. Collectively, these findings revealed EZH2 maintaining CCS-like cell characteristics by arresting the cell cycle at the G1/S phase. These results indicate a new approach to CRC therapy.

Perioperative conditions and long-term survival of patients with non-small cell lung cancer after thoracoscopic lobectomy / 中国内镜杂志

Objective To analyze the perioperative conditions and long-term survival of patients with non-small cell lung cancer (NSCLC) after thoracoscopic lobectomy. Methods 119 patients with NSCLC underwent thoracoscopic lobectomy from January 2006 to December 2012 were enrolled in the study, then collecting and analyzing their perioperative indicators, pathological results and follow-up data. Results 9 patients converted to thoracotomy with a conversion rate of 7.0 %. The median operation time, the median intraoperative blood loss and off-bed activity time were 170 min (65~440 min), 90 ml (15~3 000 ml) and (32.9 ± 16.3) h after operation respectively. The time and amount of postoperative drainage, the length of hospital stay were (6.7 ± 3.2) d, (1 690.0 ± 410.5) ml, (9.2 ± 4.0) d respectively. The incidence of perioperative mortality and postoperative complications were 0.8 %, 13.4 % respectively. For postoperative pathological type, 96 cases of adenocarcinoma, 19 cases of squamous carcinoma, 2 cases of adenosquamous carcinoma and 2 cases of large cell carcinoma. For discharge patients, the median follow-up time was 34.5 months (0 ~ 102 months). The incidence of local recurrence and distant metastasis in observation group were 5.0 % and 17.6 % respectively. 1-year overall survival (OS) and disease free survival (DFS) were 85.3 % and 79.5 %, 3-year OS and DFS were 69.8 % and 64.8 %, 5-year OS and DFS were 60.8 %and 58.6 % respectively. There was no significant difference in 1-year, 3-year and 5-year OS and DFS between adenocarcinoma and squamous carcinoma (P > 0.05) while there were significant difference in local recurrence and distant metastasis among different stages (P < 0.05). In addition to slightly low OS, DFS of Ⅲ a , Ⅲ b and Ⅳ DFS and OS, the overall living conditions among all stage were similar. Conclusions The long-term survival condition of thoracoscopic lobectomy for NSCLC is ideal, and it’s a safe and effective operation, worthy of clinical promoting.

Development of three-dimensional breast cancer cell culture drug resistance model / 生理学报

The aim of the present study was to develop three-dimensional (3D) culture model, a more pathologically relevant model, of human breast cancer for drug resistance study. MCF-7 cells were embedded within collagen gel to establish 3D culture model. Cellular morphology was observed using Carmine and HE staining. Cell proliferation was evaluated by CCK-8 assay, and cell activity was detected by Live/Dead staining kit. Drug sensitivities of the 3D culture to doxorubicin, carboplatin, 5-fluorouracil were assayed and compared with those of monolayer (2D) culture. In addition, the levels of drug resistance-related genes P-glycoprotein (P-gp), mrp2 mRNA expressions were detected by real time RT-PCR. Expression level of P-gp protein was detected by Western blot. The results showed that MCF-7 cells in 3D culture formed a number of cell aggregates, and most of them displayed good cell viability. The IC50 values of doxorubicin, carboplatin, 5-fluorouracil were all increased significantly in 3D culture compared with those in 2D culture. Moreover, compared with MCF-7 cells in 2D culture, the cells in 3D culture showed increased mRNA levels of P-gp and mrp2, as well as up-regulated protein expression of P-gp. These results suggest that in vitro collagen-embedded culture system of human breast cancer cells represents an improved pathologically relevant 3D microenvironment for breast cancer cells, providing a robust tool to explore the mechanism of drug resistance of cancer cells.

Brain MRI and clinical characteristics of maple syrup urine disease / 实用放射学杂志

Objective To investigate the characteristics of brain MRI in the patients with maple syrup urine disease(MSUD). Methods Nine patients with MSUD were diagnosed by gas chromatography mass spectrometry,tandem mass spectrometry and gene test.The MRI,clinical featuresand laboratory tests were analyzed.Results The 9 patients onset age were 3 days to 6 years old.The symptoms were varied such as poor response,lethargy,seizures and learning difficulties.Remarkable elevations of blood levels of leucine and valine were found in all patients.All patients had MRI examination,2 of them also took the examination of proton magnetic resonance spectroscopy (1 H-MRS).Involving cerebellar hemisphere,cerebellar peduncle,cerebral peduncle,brain stem,globus pallidus in 5 cases respectively,thalamus and posterior limb of internal capsule in 4 cases,centrum semiovale in 3 cases.2 cases also showed abnormal signal in corpus callosum,occipital,deep temporal lobe,and frontal lobe,parietal lobe.All lesions showed mild low signal intensity in T1 ,mild high signal intensity in T2 and obvious high signal intensity in DWI,except one case.1 H-MRS did not show a methyl resonance peak at 0.9 ppm in the two patients.Conclusion The MSUD lacked of specific clinical features.The MRI characteristics are the myelinated white matter such as the cerebellar hemispheres,posterior limb of the internal capsule,the brainstem,cerebellar peduncle,cerebral peduncle showing high signal in DWI.

Comparison of posterior capsule opacification at 360-degree square edge hydrophilic and sharp edge hydrophobic acrylic intraocular lens in diabetic patients.

AIM: To compare posterior capsule opacification (PCO) degree and visual functions after phacoemulsification in eyes implanted with 360-degree square edge hydrophilic acrylic intraocular lens (IOL) (570C C-flex, Rayner) and sharp edge hydrophobic acrylic IOL (Sensar AR40e, AMO) in diabetic patients. METHODS: Sixty diabetic patients underwent uneventful phacoemulsification and randomly implanted one of the two IOLs. The PCO value was measured by retroillumination photographs and Evaluation of Posterior Capsule Opacification (EPCO) 2000 image-analysis software at 1, 6, 12, and 24mo after surgery. Visual acuity, and contrast sensitivity in photopic and mesopic conditions were also examined at each follow up time point. The incidence of eye that required Nd:YAG laser posterior capsulotomy were also compared. RESULTS: There was not any statistically significant difference in PCO scores between Rayner C-flex 570C group and Sensar AR40e group at each follow up time point. Visual acuity, Nd:YAG capsulotomy incidence and contrast sensitivity also had no significant difference during the 24mo follow-up. CONCLUSION: For diabetic patients, Rayner 570C C-flex and Sensar AR40e IOLs are same effective for prevent PCO. The 360-degree square edge design maybe is a good alternative technique to improve PCO prevention.

Neuropilin-2 mediates lymphangiogenesis of colorectal carcinoma via a VEGFC/VEGFR3 independent signaling.

Lymphangiogenesis critically contributes to the lymphatic metastasis of colorectal carcinomas (CRCs), but the underlying mechanism of CRC lymphangiogenesis remains largely elusive. We have previously demonstrated that Semaphorin-3F (SEMA3F) is critically involved in CRC metastasis, and the receptor of SEMA3F, neuropilin-2 (NRP2), originally described as an axon guiding chemorepulsant implicated in nerve development, has been suggested in promoting lymphangiogenesis via acting as an obligate co-receptor of VEGFR3 cooperatively enhancing the activity of VEGF-C. Our present study revealed that in colorectal carcinomas, NRP2 expression levels of tumor-associated lymphatic endothelial cells (LECs) are significantly correlated with the density of tumor lymphatic vessels. In vitro, activation of NRP2 in LECs substantially facilitates their migration, sprouting, and tubulogenesis capacity via regulating the rearrangement of cytoskeleton polarity. In vivo model further showed that in the xenografts generated from SEMA3F knockdown CRC cells, NRP2 is substantially activated in tumor-associated LECs, resulting in a significantly increased tumor lymphangiogenesis. Further evidence demonstrated that CRC cell induces the activation of NRP2 in LECs to promote tumor lymphangiogenesis via integrinα9ß1/FAK/Erk pathway independent VEGF-C/VEGFR3 signaling. Our study for the first time revealed the novel molecular mechanism of NRP2-mediated-lymphangiogenesis in CRCs, suggesting NRP2 as a potential therapeutic target in preventing lymphatic metastasis of CRCs.

Planar integrated metasurfaces for highly-collimated terahertz quantum cascade lasers.

We report planar integration of tapered terahertz (THz) frequency quantum cascade lasers (QCLs) with metasurface waveguides that are designed to be spoof surface plasmon (SSP) out-couplers by introducing periodically arranged SSP scatterers. The resulting surface-emitting THz beam profile is highly collimated with a divergence as narrow as ~4° × 10°, which indicates a good waveguiding property of the metasurface waveguide. In addition, the low background THz power implies a high coupling efficiency for the THz radiation from the laser cavity to the metasurface structure. Furthermore, since all the structures are in-plane, this scheme provides a promising platform where well-established surface plasmon/metasurface techniques can be employed to engineer the emitted beam of THz QCLs controllably and flexibly. More importantly, an integrated active THz photonic circuit for sensing and communication applications could be constructed by incorporating other optoelectronic devices such as Schottky diode THz mixers, and graphene modulators and photodetectors.