Search

The cross-polarization scattering (CPS) system for magnetic fluctuation measurements in the Experimental Advanced Superconducting Tokamak (EAST) has been designed and installed. Different from the Doppler reflectometer (DR) system, the CPS system detects the perpendicular polarization of the electromagnetic wave induced by magnetic fluctuations B̃. The CPS system in the EAST has been developed from the existing Doppler reflectometer system, and they are integrated together for simultaneous measurement of magnetic and density fluctuations. Ray-tracing simulations are used to calculate the scattering locations and the wavenumber coverage of the magnetic fluctuation for CPS. In the experiments, the CPS and DR system data were different in Doppler shift, amplitude, and spectrum broadening. In this article, the hardware design, the ray tracing, and the preliminary results of the system in the EAST are presented.

Non-small cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. Bupivacaine serves as a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of bupivacaine in the NSCLC development remains elusive. Here, we tried to investigate the impact of bupivacaine on the NSCLC progression. Significantly, we revealed that bupivacaine was able to reduce the proliferation and induce the apoptosis of NSCLC cells. Bupivacaine could attenuate the invasion and migration in the cells. Mechanically, the treatment of bupivacaine increased the expression ratio of light chain 3B-II (LC3B-II)/LC3B-I and the expression of Beclin-1 in the NSCLC cells. Meanwhile, the expression of the autophagic adaptor protein p62 was decreased by bupivacaine treatment in the cells. The treatment of bupivacaine attenuated the phosphorylation of AKT and mTOR in the NSCLC cells. The AKT activator SC79 and autophagy inhibitor 3-methyladenine (3-MA) reversed the bupivacaine-inhibited phosphorylation of AKT and mTOR and bupivacaine-induced autophagy, as well as the bupivacaine-attenuated NSCLC progression in the cells. Bupivacaine could inhibit the tumor growth in vivo . In conclusion, we discovered that the local anesthetic bupivacaine inhibited the progression of NSCLC by inducing autophagy through Akt/mTOR signaling. Our finding provides new insights into the mechanism by which bupivacaine attenuates the development of NSCLC. Bupivacaine may serve as a potential anti-tumor candidate for the therapeutic strategy of NSCLC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gu, Liu, Xie, Ma, Cui, Yang and He.)

Chemical investigation of Jasminum pentaneurum Hand.-Mazz led to the isolation and identification of 12 compounds, which included one new secoiridoid glycoside, 10-(3-hydroxy-4-methoxy-benzoate)-ligustroside ( 4 ), three secoiridoid glycosides ( 1 - 3 ), and eight phenols ( 5-12 ). All compounds were reported for the first time from this plant. Their structures were elucidated based on extensive spectroscopic data analysis, including HR-ESI-MS, UV, IR, 1 D, and 2 D NMR. The absolute configuration of the new one ( 4 ) was further elucidated by comparison of its experimental and calculated quantum chemical electronic circular dichroism (ECD) spectra. All the isolates were assayed for their inhibitory activity on four human cancer cells. Compound 11 exhibited inhibitory effects against three human cancer cells SK-MES-1, SMMC-7721 and SGC-7901 with IC 50 values ranging from 83.0 to 172.0 μM.

Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01)., Competing Interests: None

Aims: To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE., Methods: Three clinical trials with branded acarbose were conducted in healthy subjects, including a pilot study (Study I, n = 11, 50 and 100 mg), a 2×2 crossover BE study (Study II, n = 36, 100 mg) and a 4×4 Williams study (Study III, n = 16, 50/100/150 mg). Serum glucose concentrations were measured by the glucose oxidase method., Results: In Study I, compared with 50 mg acarbose, only 100 mg acarbose had a significantly lower C max0-4h than that of sucrose administration alone (7.96 ± 0.83 mmol/L vs 6.78 ± 1.02 mmol/L, P < .05). In Study II, the geometric mean ratios of the test formulation to the reference formulation (both formulations were the branded drug) for FDA PD metrics, ΔC max0-4h and ΔAUC 0-4h , were 0.903 and 0.776, respectively, and the 90% confidence intervals were 67.44-120.90 and 53.65-112.13, respectively. The geometric mean ratios (confidence interval) for possible optimal evaluation PD metrics (C max0-2h and AUC 0-2h ) were 1.035 (94.23-112.68) and 0.982 (89.28-107.17), respectively. Further, C max0-2h and AUC 0-2h also met the sensitivity requirements for BE evaluation in Study III., Conclusion: Considering the mechanisms of action of acarbose, the PD effect was shown to be dose independent during the 2-4 hours postadministration of acarbose. Hence PD metrics based on the serum glucose concentration from 0 to 2 hours (C max0-2h and AUC 0-2h ) are more sensitive than the FDA-recommended PD metrics for acarbose BE evaluation from 0-4 hours (ΔC max0-4h and ΔAUC 0-4h ). The trial has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR1800015795, ChiCTR-IIR-17013918, ChiCTR-IIR-17011903). All subjects provided written informed consent before screening., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: In China, less than one third of infants under 6 months of age are being exclusively breastfed. Maternal rural-to-urban migration contributes to these low rates of breastfeeding practices. Therefore, the aim of this study was to assess the prevalence of breastfeeding practices and associated factors among rural-to-urban migrant children and local children with infants aged 0-12 months in China, 2018., Methods: Data were collected from a population-based cross-sectional survey in 2018 that included 6995 infants from eight urban areas (four metropolis and four medium sized/small cities) in China. The prevalence of breastfeeding practices was calculated using a 24-h recall questionnaire for all infants aged under 12 months. Logistic regression was conducted to examine the association between the prevalence of breastfeeding practices and maternal migrant status, after adjusting for sociodemographic characteristics, mother-infant health information and supportive information. For exclusive breastfeeding, we further analyzed its association with maternal rural-to-urban migration, stratified by maternal education level, maternal resident place and maternal ethnicity, respectively., Results: The overall prevalence of ever breastfeeding, exclusive breastfeeding, predominant breastfeeding and age-appropriate breastfeeding (exclusive breastfeeding of infants under 6 months of age and complementary feeding from six to 12 months of age) was 97.51, 29.84, 59.89 and 45.07%, respectively. Rural-to-urban migrant children were less likely to be exclusively breastfed compared to local children (AOR 0.81, 95% CI 0.68, 0.95). Stratified by different sociodemographic variables, a negative association between exclusive breastfeeding and rural-to-urban migration was only found in the group with high education level, in the group living in metropolis and in the group of minorities, respectively., Conclusions: The overall prevalence of breastfeeding practices was low in both rural-to-urban migrant children and local children. Besides common strategies, special approaches should be provided for urban highly educated migrants.

Traumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduces PTEN expression in adult sensory neurons; however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Temporomandibular disorder (TMD) is a complicated and multi‑factorial disease related to inflammation and cartilage destruction. Intra‑articular injection of xanthan gum (XG) has been demonstrated to protect the joint cartilage and reduce osteoarthritis progression. However, the role and mechanism of XG in TMD is still unclear. In the present study, chondrocytes were isolated from rats and identified by immunofluorescence. Cells were stimulated by XG or interleukin (IL)‑1β. Cell viability was analyzed by MTT assay. Tumor necrosis factor α (TNF‑α) and IL‑6 levels were determined by ELISA. The expression of monocyte chemoattractive protein‑1 (MCP‑1), inducible nitric oxide synthase (iNOS), collagens, matrix metalloproteinases (MMPs), peptidyl‑prolyl isomerase 1 (Pin1) and phosphorylated nuclear factor κB (NF‑κB) p65 (p‑p65) was analyzed by quantitative PCR or western blotting. MMP activity was assessed by gelatin zymography. Compared with the control, XG treatment partially reversed the IL‑1β‑reduced cell viability. In addition, IL‑1β stimulation increased inflammatory cytokine expression, including TNF‑α, IL‑6 secretion, MCP‑1 and iNOS expression, whereas XG treatment reduced the expression of these inflammatory cytokines compared with that of the IL‑1β‑stimulated cells. Additionally, XG increased the expression of collagen, but reduced MMP expression and activity as compared with that in the IL‑1β group. In addition, XG treatment prevented the IL‑1β‑increased Pin1 and p‑p65 expression. These data suggested that XG reduced the expression of inflammatory cytokines and may maintain the balance between collagens and MMPs partially through the Pin1/NF‑κB signaling pathway in IL‑1β‑stimulated temporomandibular chondrocytes. Therefore, XG may be useful in the treatment of TMD.

Chirality widely exists in a diverse array of biologically active molecules and life forms, and the catalytic constructions of chiral molecules have triggered a heightened interest in the fields of chemistry and materials and pharmaceutical sciences. However, the synthesis of silicon-stereogenic organosilicon compounds is generally recognized as a much more difficult task than that of carbon-stereogenic centers because of no abundant organosilicon-based chiral sources in nature. Herein, we reported a highly enantioselective rhodium-catalyzed trans-selective hydrosilylation of silicon-tethered bisalkynes to access chiral benzosiloles bearing a silicon-stereogenic center. This protocol featured with chiral Ar-BINMOL-Phos bearing hydrogen-bond donors as a privileged P-ligand for catalytic asymmetric hydrosilylation that is operationally simple and has 100% atom-economy with good functional group tolerability as well as high enantioselectivity (up to >99:1 er). Benefiting from the trans-selective hydrosilylation with the aid of Rh/Ar-BINMOL-Phos-based asymmetric catalysis, the Si-stereogenic benzosiloles exhibited pronounced aggregation-induced emission (AIE) and circularly polarized luminescence (CPL) activity., Competing Interests: Declaration of Interests The authors declare no competing financial interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To study the clinicopathologic features, immunophenotype and prognosis of pediatric-type follicular lymphoma (PTFL). Methods: Thirty-seven cases of PTFL at the Beijing Friendship Hospital, Capital Medical University, from January 2012 to March 2018 were analyzed using light microscopy, immunohistochemistry, and polymerase chain reaction (PCR), and 13 cases were also examined using fluorescence in situ hybridization (FISH). Results: The male to female ratio was 35∶2. The median age was 16 years. Thirty-one patients were clinical stage Ⅰ and 6 were stage Ⅱ, displaying enlargement of lymph node in the head and neck regions. Follow-up information was available in 32 patients. Only two patients received low-dose chemotherapy, and none of these patients had relapse or disease progression at the latest follow-up (ranging from 16 to 79 months; median, 37 months). Morphologically, the lymph node architecture was partially or totally effaced by expansile follicles lacking polarization, with a prominent "starry sky" appearance. The cytologic composition was dominated by monotonous medium to large-sized blastoid cells with round to oval nuclei, finely clumped chromatin, small nucleoli, and scant cytoplasm. Immunophenotypically, all cases were positive for CD20, CD10, and bcl-6, but negative for bcl-2, MUM1 and C-MYC. Tumor cells were restricted to the follicles. The Ki-67 immunohistochemistry demonstrated a high proliferation (50% to 90%). Moreover, the tumor cells in the examined 28 cases were negative for CD43, CD5 and CD23. PCR analysis revealed monoclonal Ig gene rearrangements in all specimens. Thirteen cases being subjected to the FISH testing lacked bcl-2 and bcl-6 translocations. Conclusion: PTFL is different from conventional follicular lymphoma in their distinct morphology, immunophenotypic and molecular features, and behaves like an highly indolent or benign tumor.

Using the commercially available and economical 6-hydroxycoumarin (6-HC) as the substrate, a dual-emission ratiometric fluorescence sensor was developed to detect tyrosinase (TYR) activity based on 3-aminophenyl boronic acid functionalized quantum dots (APBA-QDs). TYR can catalyze 6-HC, a monohydroxy compound, to form a fluorescence-enhancing o-hydroxy compound, 6,7-dihydroxycoumarin. Owing to the special covalent binding between the o -hydroxyl and boric acid groups, APBA-QDs react with 6,7-dihydroxycoumarin to form a five-membered ring ester dual-emission fluorescence probe for TYR. With an increase in TYR activity, the fluorescence at 675 nm originating from the QDs is gradually quenched, whereas that at 465 nm owing to 6,7-dihydroxycoumarin increases. Referencing the decreasing signal of the dual-emission probe at 675 nm to measure the increasing signal at 465 nm, a ratiometric fluorescence method was established to detect the TYR activity with high sensitivity and selectivity. Under the conditions optimized via response surface methodology, a linear range of 0-0.05 U/mL was obtained for the TYR activity. The detection limit was as low as 0.003 U/mL. This sensing strategy can also be adopted for the rapid screening of the TYR inhibitors.

Hydrosilylation of unsaturated carbon-carbon bonds with hydrosilanes is a very important process to access organosilicon compounds and ranks as one of the most fundamental reactions in organic chemistry. However, catalytic asymmetric hydrosilylation of activated alkenes and internal alkenes has proven elusive, due to competing reduction of carbon-carbon double bond or isomerization processes. Herein, we report a highly enantioselective Si-C coupling by hydrosilylation of carbonyl-activated alkenes using a palladium catalyst with a chiral TADDOL-derived phosphoramidite ligand, which inhibits O-hydrosilylation/olefin reduction. The stereospecific Si-C coupling/hydrosilylation of maleimides affords a series of silyl succinimides with up to 99% yield, >99:1 diastereoselectivity and >99:1 enantioselectivity. The high degree of stereoselectivity exerts remote control of axial chirality, leading to functionalized, axially chiral succinimides which are versatile building blocks. The product utility is highlighted by the enantioselective construction of N-heterocycles bearing up to three stereocenters.

A highly chemoselective platinum-catalyzed mono-lateral diboration of dialkynylsilanes for the construction of silicon-tethered alkynyl diborylalkenes is described, in which tris(4-methoxyphenyl)phosphine was found to be an effective ligand for the cis-addition of diboron agents to the silicon-tethered alkynes, and the chiral ligand (AFSi-Phos)-mediated diboration of dialkynylsilanes resulted in the desymmetric construction of silicon-stereogenic centers with promising enantioselectivity.

The Idaea effusaria belongs to Geometridae in Lepidoptera. The complete mitogenome of I. effusaria was described in this study, which is typically circular duplex molecules and 16,161 bp in length, containing the standard metazoan set of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and an A + T-rich region. The gene order is same with other lepidopterans. Except for cox1 started with CGA, all other PCGs started with the standard ATN codons. Most of the PCGs terminated with the stop codon TAA, whereas cox2 has the stop codon CAT. The phylogenetic tree showed that Larentiinae is close to Sterrhinae. The species of Ennominae form a monophyly., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

A novel and unusual palladium-catalyzed [4+2] annulation of cyclopropenes with benzosilacyclobutanes is reported. This reaction occurred through chemoselective Si-C(sp 2 ) bond activation in synergy with ring expansion/insertion of cyclopropenes to form new C(sp 2 )-C(sp 3 ) and Si-C(sp 3 ) bonds. An array of previously elusive bicyclic skeleton with high strain, silabicyclo[4.1.0]heptanes, were formed in good yields with excellent diastereoselectivity under mild conditions. An asymmetric version of the reaction with a chiral phosphoramidite ligand furnished a variety of chiral bicyclic silaheterocycle derivatives with good enantioselectivity (up to 95.5:4.5 er). Owing to the mild reaction conditions, the good stereoselectivity profile, and the ready availability of the functionalized precursors, this process constitutes a useful and straightforward strategy for the synthesis of densely functionalized silacycles., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An automatic beam alignment system based on relative reference points is developed for the Thomson scattering system on Keda Torus eXperiment. Two critical apertures around the vacuum vessel are designed to shield stray light, and a probe beam is required to go through the centers of these two apertures, which are the reference points for alignment. Since these two apertures are coated with light absorbing materials, three fibers with glowing tips are employed to indicate the centers of two apertures. CMOS cameras are used to monitor beam deviations. The misalignment correction is achieved by driving piezomotor mirror mounts via a program developed with LabVIEW, which includes the image acquisition and processing module and the deviation correction module. As a result, this system can correct beam misalignment in less than 20 s and suppress the long-term drift of laser pointing in ±10 μrad. Also, this system has the capability to correct up to about 2.3 mm of camera shift with our experiment condition.

In this study, a novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and poly(ethylene glycol)-poly(ɛ-caprolactone) (mPEG-PCL), used as a novel nanocarrier to encapsulate gambogenic acid (GNA). GNA-loaded mixed polymeric micelles (GNA-MMs) was prepared by cosolvent evaporation method. The mean average size of GNA-MMs was (83.23 ± 1.06) nm (n = 3) and entrapment efficiency (EE%) of GNA-MMs was (90.18 ± 2.59) % (n = 3) as well as (12.36 ± 0.64) % (n = 3) for drug loading (DL%). Transmission electron microscopy revealed that the GNA-MMs were spherical with "core-shell" structures. Compared with free GNA solution, in vitro release of GNA from GNA-MMs showed a two-phase sustained release profile: an initial relatively fast phase and followed by a slower release phase. Pharmacokinetic results also indicated that the GNA-MMs have longer systemic circulation time and slower plasma elimination rate than free GNA solution. Moreover, the in vitro cytotoxicity assay showed that the IC 50 values on HepG2 cells for GNA-MMs and free GNA were (5.67 ± 0.02) μM and (9.02 ± 0.03) μM, respectively. In addition, GNA-MMs significantly increased the HepG2 cellular apoptosis in a concentration-dependent manner. In conclusion, the results showed that mPEG-PLA/mPEG-PCL mixed micelles may serve as an ideal drug delivery system for GNA to prolong drug circulation time in body, enhance bioavailability and retained its potent antitumor effect., (© 2019 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Objective: Renal insufficiency may influence the pharmacokinetics of drugs. We have investigated the pharmacokinetic parameters of imrecoxib and its two main metabolites in individuals with osteoarthritis (OA) with normal renal function and renal insufficiency, respectively., Methods: This was a prospective, parallel, open, matched-group study in which 24 subjects were enrolled (renal insufficiency group, n = 12; healthy control group, n = 12). Blood samples of subjects administered 100 mg imrecoxib were collected at different time points and analyzed. Plasma concentrations of imrecoxib and its two metabolites (M1 and M2) were determined by the liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters (clearance [CL], apparent volume of distribution [V d ], maximum (or peak) serum concentration [C max ], amount of time drug is present in serum at C max [T max ], area under the curve [AUC; total drug exposure across time], mean residence time [MRT] and elimination half-life [t 1/2 ]) were calculated., Results: The demographic characteristics of the two groups were not significantly different, with the exception of renal function. The mean C max and AUC 0-t (AUC from time 0 to the last measurable concentration) of imrecoxib in the renal insufficiency group were 59 and 70%, respectively, of those of the healthy control volunteers with normal renal function, indicating a significant decline in the former group (P < 0. 05). The mean pharmacokinetic parameters of Ml in the renal insufficiency and healthy control groups did not significantly differ. In contrast, the mean C max and AUC 0-t of M2 in the renal insufficiency group were 233 and 367%, respectively, of those of the normal renal function group, indicating a significant increase in the former group (P < 0.05). The mean CL/F (clearance/bioavailability) of M2 of the renal insufficiency group was 37% of that of the normal renal function group, indicating a notable reduction in the former group (P < 0.05)., Conclusion: The exposure of imrecoxib in OA patients with renal insufficiency showed a decline compared to that in healthy subjects. However, in patients with renal insufficiency the exposure of M2 was markedly increased and the CL was noticeably reduced. These results indicate that the dosage of imrecoxib should be reduced appropriately in patients with renal insufficiency.

Objective: To investigate the pathological features and clinical manifestation of pediatric nodal marginal zone lymphoma(NMZL). Methods: Histological morphology and immunophenotype of 7 cases of pediatric NMZL were retrospectively reviewed at Beijing Friendship Hospital Affiliated to Medical University between January 2008 to October 2018. Clonal rearrangement analysis was performed. Clinical information including patient follow-up data were analyzed. Results: All 7 patients were male with a median age of 15 years aged from 10 to 26 years. All patients presented with only lymph node enlargement without B symptoms, including cervical lymph node (5 cases), preauricular lymph node (1 case) and retroauricular lymph node (1 case). Histologically, all cases showed irregular large follicles on the edges with widened marginal areas and intervesicular areas, and lesional cells were uniform with progressive transformation of germinal center centers along with a small amount of intrinsic lymphoid tissue. All 7 cases showed diffuse CD20 positivity both follicle and interfollicular region along with 30%-40% positivity in the interfollicular region (pathological region). Markers of other B-cell lymphomas werenot expressed. All 7 cases were positive for immunoglobulin(Ig) gene rearrangement. None of the patients showed no recurrence up on after follow-up for an average of 13 months. Conclusions: Pediatric NMZL is a rare type of lymphoma that has a unique morphology and occurs almost exclusively in male children and young adults and often in head and neck lymph nodes. It has an excellent prognosis. Therefore, awareness of the disease with accurate diagnosis is important.

Objective: To investigate the clinicopathological features of long-term tumor-free survival in patients with untreated primary diffuse large B-cell lymphoma (DLBCL) of the tonsil. Methods: The study included 80 consultation cases of primary tonsillar DLBCL from April 2006 to July 2017 in the Department of Pathology, Beijing Friendship Hospital, Capital Medical University. The patients were divided into two groups: experimental groups of 10 untreated patients with long-term tumor-free survival, and 70 patients who had been treated (control group). The clinical data, histopathological features, immunohistochemical staining, and molecular biology test results of the patients were analyzed retrospectively. Results: Patients who had long-term tumor-free survival with untreated primary diffuse large B-cell lymphoma had the disease mostly confined to the tonsil. Biopsy showed that the tonsil structure was only partially effaced and the lesions were relatively "fresh". EBER and FISH test for t (14;18) results were negative. Gene rearrangement detection showed monoclonality. There was statistically significant difference between the age, bcl-2 expression, CMYC protein expression and co-expression of CMYC and bcl-2 between the untreated group and the treated group( P< 0.05). Patient gender, tumor site, histological type and clinical stage showed no difference between the untreated group and the treated group ( P> 0.05); The median overall survival of the untreated group and treated group was 81 months and 20 months, respectively, and the difference was not statistically significant ( P> 0.05).In patients younger than 40 years of age, the untreated group had a statistically significant difference in primary site and CMYC protein expression compared with the treated group ( P< 0.05), and there was no statistical significance in other aspects. Conclusions: Long-term tumor-free survival patients with untreated tonsillar primary DLBCL have relatively unique clinical characteristics. There is no significant difference in the prognosis between the untreated and treated groups, indicating radiotherapy and chemotherapy may not be required and therefore, avoiding related side effects.

The development of nontoxic and stable all-inorganic perovskite nanocrystals (NCs) represents a major challenge to unlock widely practical applications in photoelectric fields. It is an effective strategy to discover nontoxic metal perovskite nanocrystals (NCs) with excellent optical properties. In addition, it has been proved that alkali metals such as rubidium (Rb) and potassium (K) have a good influence on improving the optical performance of perovskites. Hence, we reported new lead-free perovskite Rb7Bi3Cl16 single crystals, which displayed a zero-dimensional cluster structure and were composed of two kinds of octahedra with different distortions. At the same time, we synthesized its NCs, which showed a blue emission at 437 nm with a PLQY of 28.43% and presented a good optical and moisture stability for one month. The excellent moisture-stability might be attributed to their much higher ratio of Rb atoms and the ideal [BiCl6]3- octahedra on the surface, which are beneficial to form an inorganic BiOCl shell to protect the Rb7Bi3Cl16 NCs from moisture attack.

Objective: To investigate the role of microRNA-96-5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism. Methods: From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA-96-5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para-cancerous tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA-96-5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA-96-5p in gastric cancer tissue and adjacent normal tissue were detected by qRT-PCR. miRNA-96-5p mimics was transfected to BGC-823 gastric cancer cells. The effects of miRNA-96-5p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E-cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA-96-5p expressed in BGC-823 cells was detected by dual-luciferase reporter assay. Results: The median expression of miRNA-96-5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para-cancerous tissues ( P <0.05). The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para-cancerous tissues ( P <0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA-96-5p ( r =-0.613, P =0.006). The expression of miRNA-96-5p in gastric cancer cell BGC-823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84±0.15, P <0.05). The results of CCK-8 assay and Transwell assay showed that overexpression of miRNA-96-5p significantly reduced the proliferation and invasion abilities of gastric cancer cells ( P <0.05). Overexpression of miRNA-96-5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E-cadherin and downregulated the expression of vimentin. The result of dual-luciferase-3'-UTR reporter assay confirmed that miRNA-96-5p binds to the 3'UTR of FoxQ1. Conclusion: miRNA-96-5p may suppress the proliferation, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cell by down-regulation of FoxQ1.

Objective: Neural stem cells (NSCs) are multipotent stem cells that generating various neural cells, including neurons, astrocytes and oligodendrocytes. This showed that NSCs is an ideal candidate in the application of neural disease treatment. In the current study, we established a simple and efficient method to promote the viability and induce the differentiation of NSCs by stimulating with magnesium., Methods: The proliferation and differentiation of NSCs was determined by MTT assay and immunostaining. The behavior alteration was measured by rotorod test and Morris water maze., Results: Magnesium enhanced proliferation in NSCs. The ratio of Nestin+, Ki67+ and GFAP+ progenitor cells was increased in the presence of magnesium. Besides, magnesium induced the glial differentiation instead of neuronal differentiation in NSCs. By contrast, transplantation of Mg2+-treated NSCs in vivo generated more neurons. In established PD models, transplantation of Mg2+-treated NSCs could improve the symptoms and recover the memory., Conclusion: We established a simple and efficient way to promote the proliferation and induce the differentiation of NSCs. More importantly, this may also facilitate to develop a new method to neural disorder treatment.

Variants at the GTF2I repeat domain containing 1 (GTF2IRD1)-GTF2I locus are associated with primary Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders (NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders (odds ratio (OR) = 1.364, 95% confidence interval (CI) 1.019-1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) positivity (OR = 1.397, 95% CI 1.021-1.912; P = 0.036) and stratification according to coexisting autoimmune diseases (OR = 1.446, 95% CI 1.072-1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients (OR = 3.15, 95% CI 1.183-8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval number: 2016-31) on March 2, 2016., Competing Interests: None

A 5-channel Doppler backscattering system has been designed and installed in the Experimental Advanced Superconducting Tokamak (EAST). Through an I/Q-type double sideband modulator and a frequency multiplier, an array of finely spaced (Δf = 400 MHz) frequencies that span 1.6 GHz has been created. The center of the array bandwidth is tunable within the range of 75-97.8 GHz, which covers most of the W band (75-110 GHz). The incident angle can be adjusted from -4° to 12°, and the wavenumber range is 4-15 cm -1 with a wavenumber resolution of Δk/k ≤ 0.35. Ray tracing is used to calculate the scattering location and the scattering wavenumber. This article details the hardware design, the ray tracing, and the preliminary experimental results from EAST plasmas.

New strategies are needed to counter the escalating threat posed by drug-resistant fungi. The molecular chaperone Hsp90 affords a promising target because it supports survival, virulence and drug-resistance across diverse pathogens. Inhibitors of human Hsp90 under development as anticancer therapeutics, however, exert host toxicities that preclude their use as antifungals. Seeking a route to species-selectivity, we investigate the nucleotide-binding domain (NBD) of Hsp90 from the most common human fungal pathogen, Candida albicans. Here we report structures for this NBD alone, in complex with ADP or in complex with known Hsp90 inhibitors. Encouraged by the conformational flexibility revealed by these structures, we synthesize an inhibitor with >25-fold binding-selectivity for fungal Hsp90 NBD. Comparing co-crystals occupied by this probe vs. anticancer Hsp90 inhibitors revealed major, previously unreported conformational rearrangements. These insights and our probe's species-selectivity in culture support the feasibility of targeting Hsp90 as a promising antifungal strategy.

Non-small cell lung cancer (NSCLC) is one of the most fatal types of cancer with significant mortality and morbidity worldwide. MicroRNAs (miRs) have been confirmed to have positive functions in NSCLC. In the present study, we try to explore the role of miR-758 in proliferation, migration, invasion, and apoptosis of NSCLC cells by regulating high-mobility group box (HMGB) 3 (HMGB3.) NSCLC and adjacent tissues were collected. Reverse transcription quantitative PCR (RT-qPCR) was employed to detect expression of miR-758 and HMGB3 in NSCLC and adjacent tissues, in BEAS-2B cells and NSCLC cell lines. The targetted relationship between miR-758 and HMGB3 was identified by dual luciferase reporter gene assay. The effects of miR-758 on proliferation, migration, invasion, cell cycle, and apoptosis of A549 cells. MiR-758 expression was lower in NSCLC tissues, which was opposite to HMGB3 expression. The results also demonstrated that miR-758 can target HMGB3. The cells transfected with miR-758 mimic had decreased HMGB3 expression, proliferation, migration, and invasion, with more arrested cells in G 1 phase and increased apoptosis. Our results supported that the overexpression of miR-758 inhibits proliferation, migration, and invasion, and promotes apoptosis of NSCLC cells by negative regulating HMGB2. The present study may provide a novel target for NSCLC treatment., (© 2019 The Author(s).)

Morphogenetic transitions are prevalent in the fungal kingdom. For a leading human fungal pathogen, Candida albicans, the capacity to transition between yeast and filaments is key for virulence. For the model yeast Saccharomyces cerevisiae, filamentation enables nutrient acquisition. A recent functional genomic screen in S. cerevisiae identified Mfg1 as a regulator of morphogenesis that acts in complex with Flo8 and Mss11 to mediate transcriptional responses crucial for filamentation. In C. albicans, Mfg1 also interacts physically with Flo8 and Mss11 and is critical for filamentation in response to diverse cues, but the mechanisms through which it regulates morphogenesis remained elusive. Here, we explored the consequences of perturbation of Mfg1, Flo8, and Mss11 on C. albicans morphogenesis, and identified functional divergence of complex members. We observed that C. albicans Mss11 was dispensable for filamentation, and that overexpression of FLO8 caused constitutive filamentation even in the absence of Mfg1. Harnessing transcriptional profiling and chromatin immunoprecipitation coupled to microarray analysis, we identified divergence between transcriptional targets of Flo8 and Mfg1 in C. albicans. We also established that Flo8 and Mfg1 cooperatively bind to promoters of key regulators of filamentation, including TEC1, for which overexpression was sufficient to restore filamentation in the absence of Flo8 or Mfg1. To further explore the circuitry through which Mfg1 regulates morphogenesis, we employed a novel strategy to select for mutations that restore filamentation in the absence of Mfg1. Whole genome sequencing of filamentation-competent mutants revealed chromosome 6 amplification as a conserved adaptive mechanism. A key determinant of the chromosome 6 amplification is FLO8, as deletion of one allele blocked morphogenesis, and chromosome 6 was not amplified in evolved lineages for which FLO8 was re-located to a different chromosome. Thus, this work highlights rewiring of key morphogenetic regulators over evolutionary time and aneuploidy as an adaptive mechanism driving fungal morphogenesis., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: L.E.C. is a co-founder and shareholder in Bright Angel Therapeutics, a platform company for development of novel antifungal therapeutics. L.E.C. is a consultant for Boragen, a small-molecule development company focused on leveraging the unique chemical properties of boron chemistry for crop protection and animal health.

Two new compounds (1 and 2), together with six known compounds (3-8), were obtained from the Cladosporium sp. JJM22, an endophytic fungus isolated from the stem bark of the mangrove plant Ceriops tagal collected in South China Sea. Their structures were elucidated on the basis of detailed spectroscopic analysis. The absolute configurations of 1 and 2 were confirmed by the comparison of optical rotation and the CD data with those of known compounds. The inhibitory activities of the isolated compounds against six terrestrial pathogenic bacteria and human cervical carcinoma Hela cell line were evaluated. Compound 3 exhibited a broad spectrum of antibacterial activities.

Objective: To evaluate the effect of L-carnitine (LC) on low sperm acrosin activity in infertile man., Methods: A total of 240 male infertility patients with low sperm acrosin activity were randomly assigned to an LC group (n = 180) and a control group (n = 60) to be treated with LC (1g, tid) and vitamin E (VE) capsules (100 mg, tid) respectively, both for 3 months. Based on the results of routine semen analysis, the patients in the experimental group were further divided into oligozoospermia, asthenozoospermia and normozoospermia subgroups. Semen parameters and sperm acrosin activity were examined before and after treatment., Results: Totally, 220 of the patients completed the treatment and follow-up, 163 in the LC medication and 57 in the VE control group. Compared with the baseline, the percentage of progressively motile sperm (PMS) was significantly increased in the LC group after 3 months of treatment (［32.58 ± 1.13］% vs ［36.35 ± 1.26］%, P < 0.05), and so was sperm acrosin activity (［37.05±0.66］ vs ［58.61±1.93］ μIU/106 sperm, P < 0.01). Sperm concentration, PMS and sperm acrosin activity were also improved in the VE control group after treatment, but with no statistically significant difference (P > 0.05). In comparison with pretreatment, remarkable increases were observed after LC medication in sperm concentration in the oligozoospermia subgroup (［11.27 ± 0.73］ vs ［21.82 ± 4.21］ ×10⁶/ml, P < 0.01) and PMS in the asthenozoospermia patients (［20.61 ± 0.85］% vs ［29.81 ± 1.88］%, P < 0.01). And sperm acrosin activity was even higher after treatment in the asthenozoospermia than in the oligozoospermia and normozoospermia subgroups (［60.85 ± 3.04］ vs ［56.32 ± 2.86］ and ［57.09 ± 6.31］ μIU/106 sperm, P < 0.05)., Conclusions: L-carnitine can effectively elevate sperm acrosin activity in male infertility patients, particularly in those with asthenozoospermia.

From bacteria to humans, ancient stress responses enable organisms to contend with damage to both the genome and the proteome. These pathways have long been viewed as fundamentally separate responses. Yet recent discoveries from multiple fields have revealed surprising links between the two. Many DNA-damaging agents also target proteins, and mutagenesis induced by DNA damage produces variant proteins that are prone to misfolding, degradation, and aggregation. Likewise, recent studies have observed pervasive engagement of a p53-mediated response, and other factors linked to maintenance of genomic integrity, in response to misfolded protein stress. Perhaps most remarkably, protein aggregation and self-assembly has now been observed in multiple proteins that regulate the DNA damage response. The importance of these connections is highlighted by disease models of both cancer and neurodegeneration, in which compromised DNA repair machinery leads to profound defects in protein quality control, and vice versa., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To investigate the clinicopathologic features and prognosis of gastrointestinal mantle cell lymphoma (GI-MCL). Methods: Clinical data of 38 GI-MCL patients diagnosed at Beijing Friendship Hospital from January 2002 to January 2016 were retrospectively reviewed morphologically and immunophenotypically. IgH/CCND1 gene fusion was assessed by fluorescent in situ hybridization (FISH). For comparison, 60 cases of non-GI-MCL were randomly selected to extract the differences inclinicopathological features and patient survival between the two groups. Results: Of 38 patients with GI-MCL, the median age was 62 years (range: 35-78 years, 23 males and 15 females), of which patients of 60 years of age or older accounted for 55.3%. Patients with clinical course of less than 6 months accounted for 81.1%(30/37). The main symptoms included abdominal pain, diarrhea, anorexia and hematochezia. Those with B symptoms accounted for 32.4%(12/37). The tumor most often involved lleocecal region (57.9%, 22/38), followed by rectum (36.8%, 14/38) and sigmoid colon (28.9%, 11/37), and the stomach accounted for 18.4%(14/38). Endoscopic polypoid lesions were found in 33 cases (86.8%, 33/38), of which 22 cases (66.7%, 22/33) were multiple. Five cases (13.2%, 5/38) presented with local protuberant neoplasm. According to Ann Arbor staging, 3 cases (7.9%, 3/38) were at stage Ⅰ, 4 cases (10.5%, 4/38) were at stage Ⅱ, and 31 cases (81.6%, 31/38) were at stage Ⅳ. The number of patients with tumor involvement of abdominal and retroperitoneal lymph nodes accounted for 45.7%(16/35), including 41.7%(15/36) involving the superficial lymph node, 17.1%(6/35) involving extranodal sites, and 23.5%(8/34) having splenomegaly. All of the 38 cases were classic MCL, and the tumor was composed of uniform lymphoid cells and effacing normal mucosal structure. All tumors were positive for CD20 and CD5. 97.4% (37/38) tumors were positive for cyclin D1, and 92.0% (23/25) tumors were positive for SOX11. FISH test was positive in 1 case of cyclin D1 negative tumor. Twenty-eight patients (73.7%) had a median follow-up of 25.0 months (range: 3-79 months). The 3-year survival rate for stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ of patients were 80.0% and 69.1%, respectively ( P > 0.05). The 3-year survival rate for GI-MCL and non-GI-MCL patients were 71.7% and 72.5%, respectively ( P >0.05). Single factor analysis showed that age of >60 years and splenomegaly were correlated with a worse overall survival rate ( P <0.05). Conclusions: Gastrointestinal malaise is the most common presenting symptom in GI-MCL patients. GI-MCL more commonly involves colorectum with more frequent multiple polypoid lesions. Patients of age >60 years and with splenomegaly have poor prognosis. There is no difference in the prognosis between GI-MCL and non-GI-MCL patients.

Objective: To determine the cut-off values of Ki-67 labeling index (LI) in the histological grading of follicular lymphoma (FL). Methods: Clinicopathological data of 350 FL patients diagnosed at Beijing Friendship Hospital from June 2014 to January 2016 were analyzed retrospectively by quantitative evaluation and statistical analysis of Ki-67 LI. Results: Of the 350 patients with FL, the male and female ratio was 1.1 and the average age was (50.2±14.0) years with a median age of 51 years (range 4 to 82 years). The tumors were graded as grade Ⅰ-Ⅱ in 215 cases (61.4%), grade Ⅲ A in 105 cases (30.0%), and grade Ⅲ B in 30 cases (8.6%). The average Ki-67 values were (22.8%±8.3%) for the FL low (grade Ⅰ-Ⅱ) and (50.4%±10.7%) for high grade (Ⅲ A and Ⅲ B) and were statistically significant by Mann Whitney U test ( P <0.01). Receiver operated characteristic curve analysis showed that the best diagnostic cut-off value of low grade FL was 35% (sensitivity of 96.3% and specificity of 93.3%) with the largest area under curve (AUC=0.990, P <0.01, 95% CI for 0.982-0.998). According to the analysis of four lattice diagnostic tests, Ki-67 LI >40% was an important factor (χ 2 =230.733, P <0.01) in predicting high grade FL. When the cut-off value of Ki-67 LI was set at 40%, high grade LF could be diagnosed with the greatest sensitivity (98.1%) and specificity (87.7%). Moreover, a significant correlation between the Ki-67 LI and the pathological grade of FL ( r =0.836, P <0.01) was observed. Conclusions: Ki-67 LI of below a cut-off value of 35% is a reliable indicator of low grade FL.Ki-67 over 40% is consistent with high grade FL. These Ki-67 cut-off values may serveas an important auxiliary indicator in the grading of FL.

Based on a new technique, a tunable, multi-channel system that covers the Q - band (33-55 GHz) is presented in this article. It has a potential use of the Doppler backscattering system diagnostic that can measure the turbulence radial correlation and the perpendicular velocity of turbulence by changing the incident angle. The system consists primarily of a double-sideband (DSB) modulation and a multiplier, which creates four probing frequencies. The probing frequency enables the simultaneous analysis of the density fluctuations and flows at four distinct radial regions in tokamak plasma. The amplitude of the probing frequency can be adjusted by the initial phase of the intermediate frequency (IF) input from the double-sideband, and the typical flatness is less than 10 dB. The system was tested in the lab with a rotating grating, and the results show that the system can operate in the frequency range of 33-55 GHz with a Q-band multitude and that the power of each channel can be adjusted by the phase of the IF input of DSB.

Background: Curcumin exhibits anti-inflammatory effects and has been suggested as a treatment for inflammatory diseases. The aim of this study was to investigate the effects of curcumin on the lipopolysaccharide induced inflammatory response in rat gingival fibroblasts in vitro and ligation-induced experimental periodontitis in vivo, and to speculate the possible anti-inflammatory mechanism of curcumin., Methods: The gingival fibroblasts were incubated with different concentrations of curcumin in the absence or presence of lipopolysaccharide (LPS). Concentrations of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa-B ligand (RANKL) culture supernatants of rat gingival fibroblasts were determined by enzyme linked immunosorbent assay. The nuclear fraction of rat gingival fibroblasts was extracted and nuclear factor kappa-B (NF-κB) activation was assessed by western blotting to elucidate related mechanisms. Curcumin was given every two days by oral gavage. The gingival inflammation and alveolar bone loss between the first and second molars were observed by hematoxylin and eosin staining. Collagen fibers were observed by picro-sirius red staining. Alveolar bone loss was assessed by micro-CT analysis., Results: Curcumin attenuated the production of IL-1β and TNF-α in rat gingival fibroblasts stimulated by LPS, and inhibited the LPS-induced decrease in OPG/sRANKL ratio and NF-κB activation. Curcumin significantly reduced gingival inflammation and modulated collagen fiber and alveolar bone loss in vivo., Conclusions: curcumin modulates inflammatory activity in rat periodontitis by inhibiting NF-κB activation and decreasing the OPG/sRANKL ratio induced by LPS.

Objective: To investigate the clinicopathological features of EBV-positive T/NK cell lymphoproliferative diseases (EBV(+) T/NK-LPD). Methods: The clinical characteristics of 156 cases of EBV(+) T/NK-LPD were collected from August 2002 to March 2015 at Beijing Friendship Hospital, Capital Medical University. Immunohistochemical staining, EBER in situ hybridization and clonal analysis of TCR gene were performed. All patients were followed up. Results: There were 106 male and 50 female patients; patients' age ranged from 1 to 75 years (median 20 years). The course of the diseases before diagnosis ranged from 2 to 540 months (median 20 months). Fever was noted in 122 patients (78.2%), 108 patients had lymphadenopathy (69.2%), and 75 patients had hepatosplenomegaly (48.1%). Thirty-three cases were grade 1, 68 cases were grade 2, and 55 cases were grade 3. TCR gene arrangement analysis was performed in 45 cases, and 33 cases (73.3%) showed clonal rearrangement. The follow-up period ranged from 1-134 months, and 44 patients (28.2%) died. There was a trend of increased death rate associated with increasing grade ( P >0.05). Conclusions: There are many types of EBV(+) T/NK-LPD, and they can be classified as systemic, relatively localized and localized. The prognosis should be based on a comprehensive analysis of pathology and clinical data. There is no significant correlation between morphological grade and mortality. An important goal of therapy is to prevent serious complications.

Objective: To investigate clinicopathologic features and prognostic factors of mantle cell lymphoma(MCL). Methods: The clinical data of 349 MCL patients diagnosed at Beijing Friendship Hospital from January 2004 to January 2016 were retrospectively collected. Corresponding histological sections were reviewed. Additional studies included immunohistochemical staining using the MaxVision two-step method, IgH/CCND1 fusion gene detection by fluorescent in situ hybridization (FISH), and correlative statistical analysis. Results: Of 349 patients with MCL, the median patient age was 61 years (range: 25-83 years, M∶F=2.7∶1.0) and the age of 243 patients ranged from 51 to 70 years (69.6%). Those with B symptoms accounted for 22.4% (70/313). Most of the patients presented with superficial lymphadenopathy and the clinical stage Ⅲ-Ⅳ accounted for 76.1% (235/309). Extranodal involvement was seen in 47.9% (148/309), among which the gastrointestinal tract accounted for 31.8% (47/148) and splenic involvement accounted for 15.4% (47/305). Three hundred and nine (88.5%) cases were of classical type and 40 (11.5%) cases were of aggressive variant type, and all were composed of proliferating lymphoid cells. All the tumors were positive for CD20 and cyclin D1, and 98.6% (344/349) tumors were weakly positive or positive for CD5. FISH test was positive in 12 cases that were CD5 negative and with cyclin D1 partial expression.Two hundred and forty-three (69.6%) patients had a median follow-up of 26 months (range: 3-108 months). The 3- and 5-year overall survival rates for patients were 63.0% and 34.8%, respectively. Single factor analysis showed that age of >60 years, splenic involvement, aggressive variant type, incompletely overlapping type [Based on the degree of overlap ≥90% and <90% between the follicular dendritic cell (FDC) meshwork and tumor cells, the tumors were divided into the completely overlapped type and incompletely overlapped type] and Ki-67 index >40% had poor prognosis ( P <0.05). Multiple factor Cox proportional risk regression analysis after removing the aggressive variant type showed that age, splenic involvement, the degree of overlap between the FDC meshwork and tumor cells and Ki-67 index were independent prognostic factors for overall survival rate of MCL patients ( P <0.05). Conclusions: MCL is more commonly found among middle-aged and elderly men. Patient age, splenic involvement, degree of overlap between FDC meshwork and tumor cells and Ki-67 index are the independent prognostic indicators for MCL.

Candida albicans is a leading cause of death due to fungal infection. Treatment of systemic candidiasis often relies on echinocandins, which disrupt cell wall synthesis. Resistance is readily acquired via mutations in the drug target gene, FKS1. Both basal tolerance and resistance to echinocandins require cellular stress responses. We performed a systematic analysis of 3,030 C. albicans mutants to define circuitry governing cellular responses to echinocandins. We identified 16 genes for which deletion or transcriptional repression enhanced echinocandin susceptibility, including components of the Pkc1-MAPK signaling cascade. We discovered that the molecular chaperone Hsp90 is required for the stability of Pkc1 and Bck1, establishing key mechanisms through which Hsp90 mediates echinocandin resistance. We also discovered that perturbation of the CCT chaperonin complex causes enhanced echinocandin sensitivity, altered cell wall architecture, and aberrant septin localization. Thus, we provide insights into the mechanisms by which cellular chaperones enable crucial responses to echinocandin-induced stress., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate clinicopathological features and prognosis of tonsillar mantle cell lymphoma(TMCL). Methods: Clinical data of 25 patients with TMCL at Beijing Friendship Hospital, Capital Medical University from 2002 to 2016 were included. All the cases were reviewed microscopically. Various immunohistochemical stains were performed using the MaxVision two-step method. IgH/CCND1 gene fusion was detected by fluorescent in situ hybridization(FISH). Additionally, randomly selected 40 cases of non-tonsil MCL of the same period were compared. Results: Among all mantle cell lymphomas (MCL), TMCL accounted for 5.6%(25/449). The median age of the patients was 60 years(range: 44-82 years) with a M∶F ratio of 5.3 to 1.0. The main symptoms were sore throat and foreign body sensation and patients usually presented with enlargement or mass of tonsil. At the early stage of the disease, 18 cases(72.0%) were clinically misdiagnosed as tonsillitis. Lymph node involvement was present in 76.0%(19/25) of the patients. There were 4 cases(16.0%)with current splenic involvement, 11 cases(44.0%) with pharyngeal focal recidivism, and 3 cases(12.0%) with involvement of other non-lymphoid organs. Morphologically, tonsillar architectures were effaced at various degrees. Eighteen MCL cases showed classical type and 7 cases were blastoid variant. All tumors were positive for CD20 and cyclin D1. 92.0%(23/25) tumors showed weakly positive or positive expression for CD5. FISH test that IgH/CCND1 gene fusion was positive in two CD5 negative classical cases. 18 patients(72.0%) had a median follow-up time of 26 months(range: 6-81 months). The difference of survival rate between stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ patients was not statistically significant( P >0.05). Compared with NTMCL, TMCL was found to have higher proportion of stage Ⅰ-Ⅱ disease (χ(2)=12.789, P <0.01), lower the proportion of non-lymphatic organ involvement (χ(2)=8.125, P <0.01), and better prognosis (χ(2)=4.351, P =0.037). Conclusion: The incidence of TMCL is low and prone to be misdiagnosed as tonsillitis. Patients with TMCL are more likely at stage Ⅰ-Ⅱ at presentation and the prognosis is better than that of NTMCL.

Objective: To evaluate the clinicopathological features, diagnosis and management of primary testicular NK/T cell lymphoma (NKTCL). Methods: Six cases of primary testicular NKTCL at Beijing Friendship Hospital, Capital Medical University from January 2007 to December 2016 were retrospectively analyzed for the morphology, immunephenotype and outcome, and relevant literature was reviewed. Results: The median age of patients at diagnosis was 45 years(range 32-65 years). All patients presented with testicular masses as initial symptoms (6/6), five cases (5/6) were on the right. The lesions were confined to the testis. All patients were classified as Ann Arbor stage Ⅰ but the tumors exhibited aggressive clinical behavior. Two patients died of the disease within two months, three (3/6) had clinical remission, and one (1/6) was lost to follow-up. Morphologically, the lymphoma cells showed a diffuse growth pattern that largely effaced the interstitial tissues, and surrounded seminiferous tubules in all cases. There was also a prominent angioinvasive pattern, with focal necrosis and karyorrhexis(4/6). Cytologically, the medium-sized neoplastic cells showed scanty to moderate amount of cytoplasm and irregular folded nuclei. The immunophenotype was similar to that of nasal NKTCL: the neoplastic cells were positive for cytoplasmic CD3, CD56, cytotoxic molecules and EBV-encoded small RNA, the loss of CD5 antigen was seen in all cases. Conclusions: Primary testicular NKTCL is extremely rare, highly aggressive and is associated with a poor prognosis. There is no unified standard of treatment. Thus, at the time of diagnosis of testicular lymphoma, NKTCL should be included in the differential diagnosis.

Objective: To analyze clinical, pathological, molecular and genetic characteristics of Burkitt-like lymphoma with chromosome 11q aberration. Methods: A case of Burkitt-like lymphoma with 11q aberration was presented at Beijing Friendship Hospital in November 2016 with detailed clinicopathological features, immunophenotypes, Epstein-Barr virus(EBV) status and molecular genetic characteristics. Results: The patient was a 38-year-old man presenting with the cervical lymphadenopathy. In morphology, the tumor had the similar characteristics of Burkitt lymphoma, including diffuse infiltration of medium to large lymphoid cells, and presence of"starry sky"phenomenon. Immunophenotypically, the tumor cells were positive for CD20, CD10, bcl-6, but negative for bcl-2. MUM-1 showed weak and patchy positivity. Ki-67 index was more than 95%. C-MYC expression was seen in about 50% of tumor cells. EBV in situ hybridization was negative. IgH and IgK genes were clonally rearranged.Fluorescence in situ hybrization detection using MYC break probe was negative but ATM gene amplification on chromosome 11q was detected. The patient did not receive any chemotherapy or radiotherapy and had not recurrence during the 10 months follow-up. Conclusion: Burkitt-like lymphoma with chromosome 11q aberration has similar clinical, morphological and immunological characteristics to classic Burkitt's lymphoma.

The Epstein-Barr virus (EBV) is a ubiquitous lymphotropic herpesvirus that infects the human body through the respiratory tract. Usually, primary infection with EBV is asymptomatic and occurs early in life, however adolescents or young adults are more likely to develop a self-limited symptomatic infection, which manifests as acute infectious mononucleosis (IM). Systemic EBV-positive lymphoproliferative disease (EBV + T/NK-LPD) has been described as a disease related to chronic or persistent EBV infection after acute EBV infection, with severe IM-like symptoms. EBV + T/NK-LPD is associated with high mortality and morbidity with life-threatening complications. Information on its prognostic factors remains limited, therefore in this study, we aimed to evaluate the association between prognostic factors and mortality and complications of EBV + T/NK-LPD in China by retrospectively reviewing 173 EBV + T/NK-LPD cases. We observed that the high mortality rate of EBV + T/NK-LPD was mainly due to serious and fatal complications. Fever, lymphadenopathy, hepatosplenomegaly, EBV-encoded RNA (EBER) > 50/HPF, Ki-67 > 30%, and other visible complications were closely associated with EBV + T/NK-LPD prognosis. In addition, fever, hepatosplenomegaly, decreased WBC count, and a Ki-67 index of > 30% were risk factors for complications. Thus, disease prognosis should be based on a comprehensive analysis of pathological and clinical data. Such data will help pathologists and clinicians to pay close attention to the changes in the clinical condition of the patients as well as take precautionary measures against the occurrence of fatal complications., Competing Interests: None., (IJCEP Copyright © 2018.)

Skin wound healing involves Notch/Jagged1 signaling. However, little is known how Jag1 expression level in epidermal stem cells (ESCs) contributes to wound healing and scar formation. We applied multiple cellular and molecular techniques to examine how Jag1 expression in ESCs modulates ESCs differentiation to myofibroblasts (MFB) in vitro, interpret how Jag1 expression in ESCs is involved in wound healing and scar formation in mice, and evaluate the effects of porcine acellular dermal matrix (ADM) treatment on wound healing and scar formation. We found that Jag1, Notch1 and Hes1 expression was up-regulated in the wound tissue during the period of wound healing. Furthermore, Jag1 expression level in the ESCs was positively associated with the level of differentiation to MFB. ESC-specific knockout of Jag1 delayed wound healing and promoted scar formation in vivo. In addition, we reported that porcine ADM treatment after skin incision could accelerate wound closure and reduce scar formation in vivo. This effect was associated with decreased expression of MFB markers, including α-SMA Col-1 and Col-III in wound tissues. Finally, we confirmed that porcine ADM treatment could increase Jag1, Notch1 and Hesl expression in wound tissues. Taken together, our results suggested that ESC-specific Jag1 expression levels are critical for wound healing and scar formation, and porcine ADM treatment would be beneficial in promoting wound healing and preventing scar formation by enhancing Notch/Jagged1 signaling pathway in ESCs.

Objective: To investigate the clinicopathologic characteristics of neoplastic cell-rich mixed cellularity classical Hodgkin lymphoma(MCCHL-R) and to compare the prognosis with typical mixed cellularity classic Hodgkin lymphoma(MCCHL). Methods: Fifty-four patients with MCCHL-R(the tumor cells >10%) and 65 patients with typical MCCHL identified from 1 721 Hodgkin lymphomas were reviewed to compare the clinicopathological characteristics including morphologic and immunophenotypic features, EBV infection status, clinical therapy and overall survival. Results: The median age of the patients of MCCHL-R was 28.5 years(range: 9-76 years, male∶female=1.6∶1.0). Twenty-seven patients(50.0%) had B symptoms. Most patients had cervical lymph node involvement(81.5%, 44/54). Mediastinum and spleen involvement were seen in 69.2%(36/54) and 24.1%(13/54), respectively. Extranodal non-lymphoid organ involvement was seen in 41.3%(19/46) cases. Morphologically, lymph node architectures were effaced at various degree with large neoplastic cells of variable morphology, including Hodgkin/Reed-Sternberg(H/RS) cells and anaplastic large cells. There were abundant background heterogeneous admixtures of non-neoplastic inflammatory and accessory cells that were predominant mature small lymphocytes. All tumors were positive for CD30 and weakly positive for PAX5. Epstein-Barr encoded RNA(EBER)detectable by in situ hybridization was seen in 39.0% cases. Forty-six patients had a median follow-up time of 32.5 months(range: 5-128 months) and the 5-year survival rate for stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ patients were 91.7% and 50.1%, respectively( P <0.05). The 5-year survival rate for MCCHL-R was lower than typical MCCHL patients. Single factor analysis showed that age of >45 years, extranodal involvement and stage Ⅲ-Ⅳ were correlated with poorer 5-year survival rate( P <0.05). Multiple factors Cox proportional hazards regression showed that extranodal involvement was the independent prognostic factor( RR : 4.352, 95% CI : 1.122-16.879, P <0.05). Conclusions: MCCHL-R is more common in young people. The tumor has pathological features of classic Hodgkin lymphoma enriched with the tumor cells(>10%) and similar immunophenotype to classical Hodgkin lymphoma. Compared with typical MCCHL, extranodal disease is an independent prognostic factor of MCCHL-R.