Publications by authors named "Yuqin Zhang"

149 Publications

Gualou Guizhi Granule Suppresses LPS-Induced Inflammatory Response of Microglia and Protects against Microglia-Mediated Neurotoxicity in HT-22 via Akt/NF-B Signaling Pathways.

Evid Based Complement Alternat Med 2021 22;2021:9957459. Epub 2021 Jul 22.

People's Hospital Affiliated of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.

Neuroinflammation plays a crucial part in the commencement and advancement of ischemic stroke. Gualou Guizhi granule (GLGZG) is known to well exhibit neuroprotective effect, but it is not known whether GLGZG can regulate the inflammatory process at the cellular level in BV2 microglia cells and protect against microglia-mediated neurotoxicity in neurons. Herein, we aimed to investigate the anti-inflammatory effects of GLGZG on BV2 microglia cells and protection against microglia-mediated neurotoxicity in neurons. . The cell model of neuroinflammation was constructed by lipopolysaccharide (LPS) to observe the effect of GLGZG in the presence or absence of GLGZG. The production of nitric oxide (NO), inflammatory mediators, was detected. Moreover, potential mechanisms associated with the anti-inflammatory effect, such as inhibition of microglial activation and nuclear factor kappa B (NF-B), were also investigated. In addition, to prove whether GLGZG protects against microglia-mediated neurotoxicity, neuronal HT-22 cells were cultured in the conditioned medium. And cell survivability and neuronal apoptosis of HT-22 were evaluated. . It was found that a main regulator of inflammation, NO, is suppressed by GLGZG in BV2 microglial cells. Moreover, GLGZG dose dependently decreased the mRNA and protein levels of inducible NO synthase (iNOS) in LPS-stimulated BV2 cells. Additionally, GLGZG inhibited the expression and secretion of proinflammatory cytokines in BV2 microglial cells. Also, GLGZG inhibited LPS-activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) in BV2 microglial cells at the intracellular level. GLGZG significantly affected Akt phosphorylation: phosphorylated forms of Akt increased. To check whether GLGZG protects against microglia-mediated neurotoxicity, neuronal HT-22 cells were incubated in the conditioned medium. GLGZG showed a neuroprotective effect by promoting cell survivability and suppressing neuronal apoptosis. . GLGZG exerted its potential effects on suppressing inflammatory responses in LPS-induced BV2 cells by regulating NF-B and Akt pathways. In addition, GLGZG could protect against microglia-mediated neurotoxicity in HT-22.
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http://dx.doi.org/10.1155/2021/9957459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321734PMC
July 2021

[ biological safety study of porous zinc oxide/hydroxyapatite composite materials].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jul;35(7):847-854

Department of Orthopedics, the First People's Hospital of Yunnan Province, Kunming Yunnan, 650032, P.R.China.

Objective: To evaluate the biological safety of porous zinc oxide (ZnO)/hydroxyapatite (HA) composite materials.

Methods: The porous ZnO/HA composite materials and porous HA materials were prepared by the spark plasma sintering technology. First, the materials were characterized, including scanning electron microscopy to observe the material structure, degradation experiments to detect the degradation rate of the materials, and inductively coupled plasma emission spectrometer to detect the concentration of Zn dissolved out of the composite material degradation. Then the two kinds of material extracts were prepared for acute systemic toxicity test. Fifteen male Kunming mice were randomly divided into groups A, B, and C ( =5) and injected intraperitoneally with normal saline, HA extracts, and ZnO/HA extracts, respectively. The body mass of the mice was recorded before injection and at 24, 48, and 72 hours after injection. The liver and kidney tissues were taken at 72 hours for HE staining to evaluate the safety of the composite material. Finally, the biological safety of the material was evaluated by implantation experiment. The eighteen male New Zealand white rabbits were randomly divided into HA group and ZnO/HA group ( =9); a bilateral radius defect model (1 cm) was established, and the right forelimbs of the two groups were implanted with porous HA materials and porous ZnO/HA composite materials, respectively; the left untreated as a blank control. The general condition of the animals were observed after operation. The rabbit blood was collected at 1 day before operation and at 1 day, 1 week, 4 weeks, and 8 weeks after operation for routine blood test (inflammation-related indicators) and blood biochemistry (liver and kidney function-related indicators). X-ray films were taken at 4, 8, and 12 weeks after operation to observe the repair of bone defects.

Results: Material characterization showed that porous ZnO/HA composite materials had interconnected large and small pore structures with a pore size between 50 and 500 μm, which degraded faster than porous HA materials, and continuously and slowly dissolved Zn . The acute systemic toxicity test showed that the mice in each group had no abnormal performance after injection, and the body mass increased ( <0.05). HE staining showed that the cells shape and structure of liver and kidney tissue were normal. Animal implantation experiments showed that all rabbits survived until the experiment was completed; routine blood tests showed inflammation in each group (neutrophils, monocytes, and lymphocytes increased) at 1 day after operation, and all returned to normal at 8 weeks ( >0.05); compared with 1 day before operation, the content of inflammatory cells in the HA group increased at 1 day, 1 week, and 4 weeks after operation ( <0.05), and the ZnO/HA group increased at 1 day after operation ( <0.05); blood biochemistry showed that the liver and kidney function indexes were in the normal range; X-ray films showed that the ZnO/HA group had better osseointegration than the HA group at 4 weeks after operation.

Conclusion: The porous ZnO/HA composite material has good biological safety and good bone repair ability, which is a potential bone repair material.
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http://dx.doi.org/10.7507/1002-1892.202101123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311219PMC
July 2021

Report of the Largest Chinese Cohort With Gene Defect and Literature Review.

Front Genet 2021 1;12:683255. Epub 2021 Jul 1.

Department of Neurology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Thiamine metabolism dysfunction syndrome 2 (THMD2) is a rare metabolic disorder caused by mutations, inherited in autosomal recessive pattern. As a treatable disease, early diagnosis and therapy with vitamin supplementation is important to improve the prognosis. So far, the reported cases were mainly from Saudi Arab regions, and presented with relatively simple clinical course because of the hot spot mutation (T422A). Rare Chinese cases were described until now. In this study, we investigated 18 Chinese THMD2 patients with variable phenotypes, and identified 23 novel mutations, which expanded the genetic and clinical spectrum of the disorder. Meanwhile, we reviewed all 146 reported patients from different countries. Approximately 2/3 of patients presented with classical BTBGD, while 1/3 of patients manifested as much earlier onset and poor prognosis, including infantile Leigh-like syndrome, infantile spasms, neonatal lactic acidosis and infantile BTBGD. Literature review showed that elevated lactate in blood and CSF, as well as abnormal OXPHOS activities of muscle or skin usually correlated with infantile phenotypes, which indicated poor outcome. Brainstem involvement on MRI was more common in deceased cases. Thiamine supplementation is indispensable in the treatment of THMD2, whereas combination of biotin and thiamine is not superior to thiamine alone. But biotin supplementation does work in some patients. Genotypic-phenotypic correlation remains unclear which needs further investigation, and biallelic truncated mutations usually led to more severe phenotype.
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http://dx.doi.org/10.3389/fgene.2021.683255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281341PMC
July 2021

Stenotrophomonas strain CPCC 101271, an intestinal lifespan-prolonging bacterium for Caenorhabditis elegans that assists in host resistance to "Bacillus nematocida" colonization.

Arch Microbiol 2021 Jul 14. Epub 2021 Jul 14.

College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang, 473061, Henan, China.

The soil-dwelling, opportunistic pathogenic bacterium "Bacillus nematocida" B16 exhibits strong killing activities against a variety of pathogenic nematodes via a "Trojan horse" mechanism that can kill worm species like Caenorhabditis elegans. The bacterial strain CPCC 101271 was previously isolated from the intestines of C. elegans that were recovered from natural habitats and can serve as a probiotic for C. elegans, while also assisting in resistance to infection by the pathogenic strain B16. In this study, the lifespan of C. elegans fed with strain CPCC 101271 cells was extended by approximately 40% compared with that of worms fed with Escherichia coli OP50 cells. In addition, the colonization of C. elegans by the pathogenic bacterium "B. nematocida" B16 was inhibited when pre-fed with strain CPCC 101271. Metagenomic sequence analysis of intestinal microbiota of C. elegans fed with strain CPCC 101271 and infected with B16 revealed that pre-feeding worms with CPCC 101271 improved the diversity of the intestinal bacteria. Moreover, community structure significantly varied in coordination with Stenotrophomonas spp. and Bacillus spp. abundances when competition between strains CPCC 101271 and B16 was evaluated. In conclusion, the nematode microbiota strain CPCC 101271 assisted in its host resistance to colonization by the pathogen "Bacillus nematocida" and can also promote life span-prolongation in C. elegans. These results underscore that understanding the interactions between C. elegans microbiota and pathogens can provide new insights into achieving effective biological control of agricultural pests.
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http://dx.doi.org/10.1007/s00203-021-02467-4DOI Listing
July 2021

The molecular basis for SARS-CoV-2 binding to dog ACE2.

Nat Commun 2021 07 7;12(1):4195. Epub 2021 Jul 7.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.
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http://dx.doi.org/10.1038/s41467-021-24326-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263772PMC
July 2021

Metasurface of Combined Semicircular Rings with Orthogonal Slit Pairs for Generation of Dual Vector Beams.

Nanomaterials (Basel) 2021 Jun 29;11(7). Epub 2021 Jun 29.

College of Physics and Electronics, Shandong Normal University, Jinan 250014, China.

Manipulation of multichannel vector beams (VBs) with metasurfaces is an important topic and holds potential applications in information technology. In this paper, we propose a novel metasurface for the generation of dual VBs, which is composed of orthogonal slit pairs arranged on multiple groups of combined semicircular rings (CSRs). A group of CSRs include a right-shifted set and a left-shifted set of semicircular rings, and each set of semicircular rings has two halves of circles with different radii, sharing the same shifted center. Under the illumination of linearly polarized light, the two shifted sets of semicircular rings generate the two VBs at the shifted center positions on the observation plane. The slit units of each set are designed with independent rotation order and initial orientation angle. By adjusting the linear polarization of illumination, both two VBs with their orders and polarization states are independently controlled simultaneously. The principle and design are demonstrated by the finite-difference time domain (FDTD) simulation. The work is of significance for miniatured devices of VB generators and for related applications.
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http://dx.doi.org/10.3390/nano11071718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306331PMC
June 2021

Design and analysis of trench-assisted dual-mode multi-core fiber with large-mode-field-area.

Appl Opt 2021 Jun;60(16):4698-4705

A novel trench-assisted dual-mode multi-core fiber with large-mode-field-area is proposed. The structure consists of 17 conventional cores and two air holes according to a regular hexagon, which can realize strict dual-mode transmission. The structural parameters' effect on mode transmission characteristics, mode-field-area, and bending loss are analyzed systematically. By optimizing the structural parameters, the mode-field-area of the fundamental mode can reach ${2100.619}\;{{\unicode{x00B5}{\rm m}}^2}$. The introduction of the trench with a lower refractive index than cladding can reduce the bending loss to ${9.88} \times {{10}^{- 4}}\;{\rm dB}/{\rm m}$ when the bending radius is 2.3 cm. Besides, the structural design is flexible, and the manufacturing process is simple, which has broad application prospects.
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http://dx.doi.org/10.1364/AO.421030DOI Listing
June 2021

Efficacy of Xiang-Sha-Liu-Jun-Zi on chemotherapy-induced nausea and vomiting: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 May;100(19):e25848

The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, PR China.

Background: Cancer is the main cause of death worldwide, and chemotherapy is the basic method of treating cancer. However, chemotherapy-induced nausea and vomiting (CINV) is the most common side effect of chemotherapy, and conventional antiemetics for the treatment of CINV also have side effects. At present, a large number of randomized controlled trials have shown that Xiang-Sha-Liu-Jun-Zi (XSLJZ) can effectively treat CINV, but there is no systematic review. Therefore, this systematic review aims to discuss the effectiveness of XSLJZ in the treatment of CINV.

Methods: Search for relevant documents in the Chinese and English databases, and the search time is limited to March 2021. Databases include Embase, Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure, Chongqing VIP Information Resource Integration Service Platform, Wanfang Data, Chinese Biomedical Literature, etc. We will search the international clinical trial registration platform and the Chinese clinical trial registration platform to find ongoing and unpublished clinical trials. Randomized controlled trial of the efficacy of XSLJZ in the treatment of CINV were collected. After screening the literature according to the inclusion and exclusion criteria, two researchers independently extracted the data. The effective rate of treatment is the main outcome indicator of this study. The secondary indicators of this study include the incidence of adverse reactions and the improvement rate of quality of life. RevMan 5.3.5 software was used for statistical analysis. Grades of Recommendation, Assessment, Development, and Evaluation system will be used to evaluate the quality evidence for each outcome.

Results: This study will provide the latest evidence for the treatment of CINV by XSLJZ.

Conclusion: : To evaluate the efficacy of XSLJZ in the treatment of CINV.

Unique Inplasy Number: INPLASY202140079.
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http://dx.doi.org/10.1097/MD.0000000000025848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133094PMC
May 2021

UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer.

Cell Death Dis 2021 05 21;12(6):519. Epub 2021 May 21.

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China.

UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 in oxaliplatin resistance in colorectal cancer (CRC) remains unknown. In our study, UPF1 is upregulated in CRC in mRNA and protein levels and overexpression of UPF1 predicts a poor overall survival (OS) and recurrence-free survival (RFS) in CRC patients and is an independent risk factor for recurrence. UPF1 promotes chemoresistance to oxaliplatin in vitro and in vivo. UPF1-induced oxaliplatin resistance can be associated with interaction between zinc finger of UPF1 and Toprim of TOP2A and increasing phosphorylated TOP2A in a SMG1-dependent manner. Moreover, UPF1 maintains stemness in a TOP2A-dependent manner in CRC. Taken together, UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced chemoresistance to oxaliplatin in CRC, which may result from regulation of TOP2A activity and maintenance of stemness. Our findings could provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.
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http://dx.doi.org/10.1038/s41419-021-03798-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140095PMC
May 2021

A novel nomogram based on prognostic factors for predicting venous thrombosis risk in lymphoma patients.

Leuk Lymphoma 2021 May 8:1-9. Epub 2021 May 8.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Lymphoma-associated venous thromboembolism (VTE) can be a serious complication in lymphoma patients. We designed a nomogram as a guide to estimate the VTE risk in lymphoma patients. We retrospectively analyzed 555 Chinese lymphoma patients who were newly diagnosed at West China Hospital. The nomogram was generated based on multivariate regression coefficients. The multivariate analysis indicated that advanced clinical stage ( < .001*), Hodgkin lymphoma ( = .045*), and prechemotherapy Hb level <115 g/L ( = .01*) were independent risk factors for VTE in lymphoma patients. A calibration plot and the area under the receiver operating characteristic curve were used to validate the novel nomogram. The nomogram displayed a good C-index (0.73), and the calibration plot showed excellent agreement between the predicted and actual probabilities. The AUROC of the nomogram was 0.731, demonstrating a strong discriminatory ability. Notably, the predictive value of the nomogram was better than the Khorana risk score.
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http://dx.doi.org/10.1080/10428194.2021.1913149DOI Listing
May 2021

Optical Spin Hall Effect in Closed Elliptical Plasmonic Nanoslit with Noncircular Symmetry.

Nanomaterials (Basel) 2021 Mar 26;11(4). Epub 2021 Mar 26.

College of Physics and Electronics, Shandong Normal University, Jinan 250014, China.

We investigated the optical spin Hall effect (OSHE) of the light field from a closed elliptical metallic curvilinear nanoslit instead of the usual truncated curvilinear nanoslit. By making use of the characteristic bright spots in the light field formed by the noncircular symmetry of the elliptical slit and by introducing a method to separate the incident spin component (ISC) and converted spin component (CSC) of the output field, the OSHE manifested in the spot shifts in the CSC was more clearly observable and easily measurable. The slope of the elliptical slit, which was inverse along the principal axes, provided a geometric phase gradient to yield the opposite shifts of the characteristic spots in centrosymmetry, with a double shift achieved between the spots. Regarding the mechanism of this phenomenon, the flip of the spin angular momentum (SAM) of CSC gave rise to an extrinsic orbital angular momentum corresponding to the shifts of the wavelet profiles of slit elements in the same rotational direction to satisfy the conservation law. The analytical calculation and simulation of finite-difference time domain were performed for both the slit element and the whole slit ellipse, and the evolutions of the spot shifts as well as the underlying OSHE with the parameters of the ellipse were achieved. Experimental demonstrations were conducted and had consistent results. This study could be of great significance for subjects related to the applications of the OSHE.
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http://dx.doi.org/10.3390/nano11040851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066872PMC
March 2021

Membrane receptor-mediated mechano-transduction maintains cell integrity during pollen tube growth within the pistil.

Dev Cell 2021 Apr 22;56(7):1030-1042.e6. Epub 2021 Mar 22.

Department of Botany and Plant Sciences and Institute for Integrative Genome Biology, University of California, Riverside, Riverside, CA 92521, USA. Electronic address:

Invasive or penetrative growth is critical for developmental and reproductive processes (e.g., pollen tube penetration of pistils) and disease progression (e.g., cancer metastasis and fungal hyphae invasion). The invading or penetrating cells experience drastic changes in mechanical pressure from the surroundings and must balance growth with cell integrity. Here, we show that Arabidopsis pollen tubes sense and/or respond to mechanical changes via a cell-surface receptor kinase Buddha's Paper Seal 1 (BUPS1) while emerging from compressing female tissues. BUPS1-defective pollen tubes fail to maintain cell integrity after emergence from these tissues. The mechano-transduction function of BUPS1 is established by using a microfluidic channel device mimicking the mechanical features of the in vivo growth path. BUPS1-based mechano-transduction activates Rho-like GTPase from Plant 1 (ROP1) GTPase to promote exocytosis that facilitates secretion of BUPS1's ligands for mechanical signal amplification and cell wall rigidification in pollen tubes. These findings uncover a membrane receptor-based mechano-transduction system for cells to cope with the physical challenges during invasive or penetrative growth.
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http://dx.doi.org/10.1016/j.devcel.2021.02.030DOI Listing
April 2021

Gualou Guizhi Granule Protects against OGD/R-Induced Injury by Inhibiting Cell Pyroptosis via the PI3K/Akt Signaling Pathway.

Evid Based Complement Alternat Med 2021 8;2021:6613572. Epub 2021 Mar 8.

Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.

Pyroptosis is a proinflammatory form of regulated cell death that plays an important role in ischemic stroke. Gualou Guizhi granule (GLGZG) is a classic prescription that has been shown to exert neuroprotective effects against cerebral ischemia reperfusion injury. In the present study, we examined the involvement of pyroptosis and its associated mechanism in protecting nerve function. . Primary neurons were exposed to oxygen-glucose deprivation and reperfusion (OGD/R) conditions in the presence or absence of GLGZG. Cellular viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay. The number of apoptoic cells was detected by NeuN and NSE protein expression. The expression levels of the pyroptosis markers, namely, NOD-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, interleukin-18 (IL-18), and IL-1 were determined by quantitative real-time PCR analysis, western blot, and ELISA analyses as appropriate. Moreover, the expression levels of the PI3K/Akt pathway key proteins were determined by quantitative real-time PCR analysis and western blot assays. To determine the PI3K/Akt pathway involvement in GLGZG-mediated neuroprotection, the PI3K inhibitor LY294002 (LY, 10 M) was added. The expression levels of NeuN, Akt, and p-Akt were evaluated. . It was found that GLGZG could inhibit OGD/R-induced cell apoptosis, increase neuronal cell viability, decrease the production of IL-18 and IL-1, and downregulate the expression levels of pyroptosis markers (NLRP3, ASC, and caspase-1). Furthermore, GLGZG could modulate the PI3K/Akt signaling pathway. Pharmacological inhibition of the PI3K pathway not only abrogated the effects of GLGZG on Akt but also neutralized its prosurvival and antipyroptotic actions. . The findings indicated that GLGZG pretreatment effectively reduced OGD/R-induced injury by inhibiting cell pyroptosis and activating the PI3K/Akt pathway. These data provide important evidence for the therapeutic applications of this regimen in ischemic stroke.
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http://dx.doi.org/10.1155/2021/6613572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960020PMC
March 2021

Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial.

Lancet Oncol 2021 04 8;22(4):439-449. Epub 2021 Mar 8.

Ovarian Cancer Program, Department of Gynaecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Background: The benefits of secondary cytoreduction for platinum-sensitive relapsed ovarian cancer are still widely debated. We aimed to assess the efficacy of secondary cytoreduction plus chemotherapy versus chemotherapy alone in this patient population.

Methods: This multicentre, open-label, randomised, controlled, phase 3 trial (SOC-1), was done in four primarily academic centres in China (two in Shanghai, one in Hangzhou, and one in Guangzhou). Eligible patients were women aged 18 years and older with platinum-sensitive relapsed epithelial ovarian cancer with a platinum-free interval of at least 6 months after the end of first-line platinum-based chemotherapy and were predicted to have potentially resectable disease according to the international model (iMODEL) score and PET-CT imaging. iMODEL score was calculated using six variables: International Federation of Gynecology and Obstetrics stage, residual disease after primary surgery, platinum-free interval, Eastern Cooperative Oncology Group performance status, serum level of cancer antigen 125 at recurrence, and presence of ascites at recurrence. An iMODEL score of 4·7 or lower predicted a potentially complete resection. As per a protocol amendment, patients with an iMODEL score of more than 4·7 could only be included if the serum level of cancer antigen 125 was more than 105 U/mL, but the principal investigators assessed the disease to be resectable by PET-CT. Eligible participants were randomly assigned (1:1) via a permuted block design (block size of six) and stratified by study centre, iMODEL score, residual disease at primary surgery, and enrolment in the Shanghai Gynecologic Oncology Group SUNNY trial, to undergo secondary cytoreductive surgery followed by intravenous chemotherapy (six 3-weekly cycles of intravenous paclitaxel [175 mg/m] or docetaxel [75 mg/m] combined with intravenous carboplatin [area under the curve of 5 mg/mL per min]; surgery group) or intravenous chemotherapy alone (no surgery group). Primary endpoints were progression-free survival and overall survival, analysed in all participants randomly assigned to treatment, regardless of treatment received (intention-to-treat [ITT] population). Here, we report the final analysis of progression-free survival and the prespecified interim analysis of overall survival. Safety was assessed in all participants who received their assigned treatment and had available adverse event data. This study is registered with ClinicalTrials.gov, NCT01611766, and is ongoing but closed to accrual.

Findings: Between July 19, 2012, and June 3, 2019, 357 patients were recruited and randomly assigned to the surgery group (182) or the no surgery group (175; ITT population). Median follow-up was 36·0 months (IQR 18·1-58·3). In the no surgery group, 11 (6%) of 175 participants had secondary cytoreduction during second-line therapy while 48 (37%) of 130 participants who had disease progression crossed-over and had surgery at a subsequent recurrence. Median progression-free survival was 17·4 months (95% CI 15·0-19·8) in the surgery group and 11·9 months (10·0-13·8) in the no surgery group (hazard ratio [HR] 0·58; 95% CI 0·45-0·74; p<0·0001). At the interim overall survival analysis, median overall survival was 58·1 months (95% CI not estimable to not estimable) in the surgery group and 53·9 months (42·2-65·5) in the no surgery group (HR 0·82, 95% CI 0·57-1·19). In the safety population, nine (5%) of 172 patients in the surgery group had grade 3-4 surgical morbidity at 30 days, and no patients in either group had died at 60 days after receiving assigned treatment. The most common grade 3-4 adverse events during chemotherapy were neutropenia (29 [17%] of 166 patients in the surgery group vs 19 [12%] of 156 patients in the no surgery group), leucopenia (14 [8%] vs eight [5%]), and anaemia (ten [6%] vs nine [6%]). Four serious adverse events occurred, all in the surgery group. No treatment-related deaths occurred in either group.

Interpretation: Secondary cytoreduction followed by chemotherapy was associated with significantly longer progression-free survival than was chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer, and patients should be counselled about the option of secondary cytoreduction in specialised centres. Long-term survival outcomes will be assessed using mature data on overall survival.

Funding: Zhongshan Development Program.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00006-1DOI Listing
April 2021

Characterization of Odontogenic Differentiation from Human Dental Pulp Stem Cells Using TMT-Based Proteomic Analysis.

Biomed Res Int 2020 10;2020:3871496. Epub 2020 Dec 10.

Guangdong Provincial Key Laboratory of Oral Diseases, Guangzhou 510055, China.

Background: The repair of dental pulp injury relies on the odontogenic differentiation of dental pulp stem cells (DPSCs). To better understand the odontogenic differentiation of DPSCs and identify proteins involved in this process, tandem mass tags (TMTs) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were applied to compare the proteomic profiles of induced and control DPSCs.

Methods: The proteins expressed during osteogenic differentiation of human DPSCs were profiled using the TMT method combined with LC-MS/MS analysis. The identified proteins were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, a protein-protein interaction (PPI) network was constructed. Two selected proteins were confirmed by western blotting (WB) analysis.

Results: A total of 223 proteins that were differentially expressed were identified. Among them, 152 proteins were significantly upregulated and 71 were downregulated in the odontogenic differentiation group compared with the control group. On the basis of biological processes in GO, the identified proteins were mainly involved in cellular processes, metabolic processes, and biological regulation, which are connected with the signaling pathways highlighted by KEGG pathway analysis. PPI networks showed that most of the differentially expressed proteins were implicated in physical or functional interaction. The protein expression levels of FBN1 and TGF-2 validated by WB were consistent with the proteomic analysis.

Conclusions: This is the first proteomic analysis of human DPSC odontogenesis using a TMT method. We identified many new differentially expressed proteins that are potential targets for pulp-dentin complex regeneration and repair.
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http://dx.doi.org/10.1155/2020/3871496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789479PMC
May 2021

CT-derived abdominal adiposity: Distributions and better predictive ability than BMI in a nationwide study of 59,429 adults in China.

Metabolism 2021 02 28;115:154456. Epub 2020 Nov 28.

National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: Although abdominal adiposity is associated with an altered cardiometabolic risk profile, the specific contribution of abdominal adipose tissue distribution remains not fully understood. Computed tomography (CT) is a well-established and precise method to measure abdominal adipose tissue distribution. The present study investigated abdominal adiposity assessed by CT in a large-scale Chinese population.

Method: A total of 59,429 adults who underwent a low dose chest CT for lung cancer screening at one of 13 health checkup centers throughout China were evaluated. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured at the center of the 2nd lumbar vertebra with Mindways quantitative CT software using the existing CT dataset without any additional radiation exposure. The ratio of visceral to total adipose tissue (TAT) areas (VAT/TAT ratio) was calculated and expressed as a percentage. Anthropometric indices including body mass index (BMI) and waist circumference were also obtained.

Results: BMI, waist circumference, VAT area, SAT area, and the VAT/TAT ratio were 25.0 ± 3.0 kg/m, 90 ± 8 cm, 194 ± 77 cm, 85 ± 41 cm, and 69.5 ± 9.1%, respectively, in men and 23.3 ± 3.1 kg/m, 79 ± 8 cm, 120 ± 57 cm, 123 ± 53 cm, and 48.9 ± 9.7% in women. With increasing age, VAT area and the VAT/TAT ratio increased in both sexes whereas SAT area decreased in men (P < 0.001 for all). After adjustment for BMI and waist circumference, older individuals showed higher VAT area and higher VAT/TAT ratio than younger subjects (P < 0.001 for all). Adjusted VAT areas in participants aged 75 or older was 45 cm (95% confidence interval [CI]: 41 cm, 50 cm) higher in men and 43 cm (95% CI: 37 cm, 49 cm) higher in women compared with participants aged 31-44 years. Additionally, differences in VAT area across age groups increased as BMI or waist circumference increased. VAT and SAT areas, but not the VAT/TAT ratio, were positively associated with BMI and waist circumference in every age group.

Conclusion: In a nationwide study conducted in China, distributions of CT-derived measures of visceral and subcutaneous adiposity were found to vary significantly between sex and age groups. Our study also revealed that the proportion of VAT (an important driver of cardiometabolic risk) could not be predicted from BMI in a Chinese population.
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http://dx.doi.org/10.1016/j.metabol.2020.154456DOI Listing
February 2021

Zelkovamycins B-E, Cyclic Octapeptides Containing Rare Amino Acid Residues from an Endophytic sp.

Org Lett 2020 12 20;22(23):9346-9350. Epub 2020 Nov 20.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P. R. China.

Four unusual cyclopeptides, zelkovamycins B-E (-), were isolated from an endophytic sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxypyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey's method, and NMR calculations. A plausible biosynthetic pathway for zelkovamycins was proposed based on gene cluster analysis. Zelkovamycin E displayed potent inhibitory activity against H1N1 influenza A virus.
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http://dx.doi.org/10.1021/acs.orglett.0c03565DOI Listing
December 2020

[Analysis of gene variant in a Chinese child affected with dihydropyrimidinase deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Nov;37(11):1241-1243

Tianjin Pediatric Research Institute, Tianjin Children's Hospital, Tianjin 300134, China.

Objective: To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency.

Methods: Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing.

Results: The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers.

Conclusion: The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.
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http://dx.doi.org/10.3760/cma.j.cn511374-20191101-00553DOI Listing
November 2020

Opportunistic Screening Using Low-Dose CT and the Prevalence of Osteoporosis in China: A Nationwide, Multicenter Study.

J Bone Miner Res 2021 Mar 4;36(3):427-435. Epub 2020 Nov 4.

National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L -L ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm ) than men (176.6 mg/cm ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm ) than men (92.1 mg/cm ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
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http://dx.doi.org/10.1002/jbmr.4187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988599PMC
March 2021

Taxonomic and Genotypical Heterogeneity of Microcystin degrading Bacterioplankton in Western Lake Erie.

Harmful Algae 2020 09 29;98:101895. Epub 2020 Aug 29.

Biological Science Department, Kent State University, Kent Ohio 44242, U.S.A.. Electronic address:

Microcystins (MCs) are among the predominant cyanotoxins that are primarily degraded by heterotrophic bacteria in various freshwater environments, including Lake Erie, a Laurentian Great Lake. However, despite the prevalence of MCs in Lake Erie basins, our knowledge about the taxonomic diversity of local MC-degrading bacteria is largely limited. The current study obtained thirty-four MC-degrading bacterial pure isolates from Lake Erie surface water and characterized their taxonomical and phenotypic identities as well as their MC-degradation rates under different pH, temperature, availability of organic substrates and with other MC-degrading isolates. Obtained MC-degrading isolates included both Gram-positive (18 isolates of Actinobacteria and Firmicutes) and Gram-negative bacteria (16 isolates of Gamma-proteobacteria); and 7 of these isolates were motile, and 13 had the capacity to form biofilms. In general, MC-degradation rates of the isolates were impacted by temperature and pH but insensitive to the presence of cyanobacterial exudates. At the optimal temperature (30-35°C) and pH (7-8), individual isolates degraded MC-LR, the most abundant MC isomer, at an average of 0.20 µg/mL/hr. With additions of cyanobacterial exudates, only Pseudomonas sp. LEw-2029, a non-motile biofilm maker, showed increased MC degradation (0.25 µg/mL/hr). Five out of nine tested dual culture mixtures showed rises in MC degradation rates than their corresponding monocultures; the highest rate reached 0.40 µg/mL/hr for the pair LEw-(1132 + 2029). PCR amplification of mlrA genes yielded negative results for all isolates; subsequent enzyme assay-Mass Spectrum analysis identified no product associated with the mlr gene-based MC degradation pathway. Collectively, our results demonstrated that a diversity of indigenous Lake Erie bacteria can degrade MCs via a novel mlr-independent pathway. Obtained MC degraders, especially Pseudomonas sp. LEw-2029, may serve as candidates for the development of biological filters to remove cyanotoxins in water treatment systems.
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http://dx.doi.org/10.1016/j.hal.2020.101895DOI Listing
September 2020

An Verification of the Effects of Paeoniflorin on Lipopolysaccharide-Exposed Microglia.

Evid Based Complement Alternat Med 2020 12;2020:5801453. Epub 2020 Oct 12.

Research Base of Traditional Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.

Background: The neuroprotective effects of Paeoniflorin (PF) are well known. Most of the evidence was verified . We attempted to perform an verification of the effects of PF in microglia.

Methods: A lipopolysaccharide- (LPS-) exposed microglia model was employed. An enzyme-linked immunosorbent assay was used to measure the levels of cytokines in the culture supernatants. A real-time polymerase chain reaction was performed to measure the mRNA expression of cytokines and M1- and M2-like genes. A western blot analysis was used to examine the expression of proteins associated with the nuclear factor-kappa B (NF-B) signaling pathway.

Results: We found that the administration of PF reversed the inflammatory response induced by LPS. It downregulated proinflammatory cytokines and upregulated anti-inflammatory cytokines. This, in turn, alleviated the oxidative injuries, downregulated the expression of M1-like genes, and upregulated the expression of M2-like genes. PF can also reverse the changes in proteins associated with the NF-B signaling pathway induced by LPS.

Conclusions: We provided evidence obtained concerning the neuroprotective effects of PF via suppressing activation of microglia, which might be associated with the NF-B signaling pathway. These findings contribute to obtaining a deeper understanding of PF, a potential new treatment for brain injuries.
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http://dx.doi.org/10.1155/2020/5801453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576368PMC
October 2020

Comparison Between Familial Colorectal Cancer Type X and Lynch Syndrome: Molecular, Clinical, and Pathological Characteristics and Pedigrees.

Front Oncol 2020 2;10:1603. Epub 2020 Sep 2.

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Objective: This study aimed to compare the molecular, clinical, and pathological characteristics and pedigrees of familial colorectal cancer type X (FCCTX) with those of Lynch syndrome (LS) to provide a theoretical basis for the management of FCCTX.

Methods: Overall, 46 cases of FCCTX and 47 LS probands and affected families were enrolled between June 2008 and September 2018 for this study. Multigene cancer panel tests that included 139 genes were performed for all patients, and variants in each group were described. The clinical, pathological, and pedigree characteristics were also compared between the two groups.

Results: In total, 42 variants were detected in 27 (58.7%) cases in the FCCTX group, with , , , , , and being the most frequently mutated genes. The mean onset age of colorectal cancer (CRC) was significantly older in the FCCTX group than in the LS group (53.57 ± 12.88 years vs. 44.36 ± 11.26 years, = -9.204, < 0.001). The proportion of patients with rectal cancer was also higher in the FCCTX group than in the LS group [43.5% (20/46) vs. 10.6% (5/47), χ = 12.823, = 0.005]. Within a median follow-up time of 53.9 ± 37.0 months, the proportion of patients who developed metachronous CRC was significantly higher in the LS group than in the FCCTX group [34.0% (16/47) vs. 13.0% (6/46), χ = 5.676, = 0.017]. When comparing pedigrees, older age at cancer onset and rectal cancer clustering were observed in the FCCTX families. A higher prevalence in male patients was also observed in the FCCTX families.

Conclusion: FCCTX is an entity distinct from LS, but its genetic etiology remains unknown. A larger multigene panel would be recommended for determining the underlying pathogenic variants. Considering the pathology and moderate penetrance of the CRC link to FCCTX, less stringent surgical treatments and colonoscopy surveillance would be preferable. Rectum preference is a typical feature of FCCTX. Colonoscopy surveillance in FCCTX families could be less intensive, and more attention should be given to male members.
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http://dx.doi.org/10.3389/fonc.2020.01603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493642PMC
September 2020

Long-term effects of ambient PM2.5 on hypertension in multi-ethnic population from Sichuan province, China: a study based on 2013 and 2018 health service surveys.

Environ Sci Pollut Res Int 2021 Feb 26;28(5):5991-6004. Epub 2020 Sep 26.

Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Hypertension, a major risk factor of many severe chronic diseases and leading cause of global disease burden, is reported to be associated with long-term exposure to PM. China's high PM pollution level has become a major public health issue. However, existing studies from China have got inconsistent results with very limited investigation into the multi-ethnic peoples. This study adds multi-ethnic evidence from Sichuan Province, southwestern China, and assesses ethnic differences of PM exposure effect on hypertension. We pooled large cross-sectional data from two surveys conducted in 2013 and 2018 to examine the association of long-term exposure to PM on prevalence of hypertension in adults aged 30 years old and above. Community-specified annual PM concentration was estimated using satellite data. Thirty-one thousand four hundred sixty-two participants with average exposure concentration of 32.8 μg/m were included. The proportions of the Han, the Tibetan, the Yi, and other ethnic people were 89.2%, 7.3%, 3.2%, and 0.3%, respectively. The adjusted odds ratio (OR) was 1.08 (95% CI, 1.04-1.12) for a 10 μg/m PM concentration increment. The adjusted ORs for the Han, the Tibetan, and the Yi were 1.08 (95% CI, 1.04-1.12), 0.03 (95% CI, 0.00-0.27), and 1.75 (95% CI, 1.28-2.38) for a 10 μg/m PM concentration increment, respectively. Stratification analysis found stronger associations in participants with chronic diseases and Yi minority population. The results showed that long-term exposure to PM may increase the risk of hypertension prevalence in Chinese multi-ethnic adults. The associations were different among ethnicities.
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http://dx.doi.org/10.1007/s11356-020-10893-yDOI Listing
February 2021

Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes.

Front Genet 2020 19;11:991. Epub 2020 Aug 19.

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

In this study, we compared the molecular, clinical, and pathological characteristics, as well as pedigrees, between patients with Lynch-like syndrome (LLS) and confirmed Lynch syndrome (LS) to develop appropriate management strategies for patients with LLS and their affected family members. Between June 2008 and September 2018, 81 patients with LLS and 47 patients with LS who developed colorectal cancer (CRC) were enrolled in this study. Multigene panel testing included 139 genes and was performed for all patients. The variants identified in each group were described, and clinicopathological characteristics and pedigrees were compared between the two groups. In the LLS group, a total of 52 variants were detected in 44 (54.3%) patients. Among the 52 variants, 17 were variants of unknown significance in mismatch repair genes, and the other most frequently mutated genes were , , , and . The proportion of early-onset patients was significantly higher among the LS probands than among the LLS probands (74.5 and 53.1%, respectively; χ = 5.712, = 0.017). On the other hand, the proportion of primary CRC developed in the rectum was higher in the LLS group than in the LS group (25.9 and 10.6%, respectively; χ = 2.358, = 0.046). There were no significant differences in the occurrence of metachronous CRC ( = 0.632) and extra-colorectal cancer (extra-CRC) ( = 0.145) between the two groups. However, analysis of pedigrees showed that more patients developed CRC in the LS families ( = 0.013), whereas more patients with extra-CRC were observed in the LLS families ( = 0.045). A higher prevalence of male patients was observed in the LLS families ( = 0.036). In conclusion, LLS should be classified as a mixed entity, containing cases of LS, other hereditary cancer syndromes, and sporadic CRC. The high risks of CRC and extra-CRCs, which were found in this study, suggest tailored management policy and surveillance should be formulated based on individual and family risk. The surveillance regimen can be based on the presence of confirmed pathogenic/likely pathogenic germline variant(s) and family history.
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http://dx.doi.org/10.3389/fgene.2020.00991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466573PMC
August 2020

Actinoplanes solisilvae sp. nov., Isolated from Birch Forest Soil.

Curr Microbiol 2020 Nov 11;77(11):3799-3806. Epub 2020 Sep 11.

Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

A novel actinomycete, designated strain LAM7112, was isolated from soil sample collected from a birch forest in Xinjiang Uygur Autonomous Region, China. The new isolate was found to be able to grow at 20-45 °C (optimum: 35 °C), pH 5.0-10.0 (optimum: 7.0) and in the presence of 0-10.0% (optimum: 3.0%) (w/v) NaCl. The isolate formed very scantily irregular sporangia containing motile spores on the substrate mycelium. Phylogenetic analysis of 16S rRNA gene sequences indicated that the new isolate was closely related to members of the family Micromonosporaceae, with highest similarites to Actinoplanes ferrugineus X-14695 (97.4%), Micromonospora zamorensis DSM 45600 (97.3%) and Micromonospora aurantiaca ATCC 27029 (97.3%). In the phylogenetic trees, strain LAM7112 formed a stable phylogenetic subclade within the genus Actinoplanes. The genomic DNA G + C content was 70.0 mol%. The major fatty acids (> 10%) were determined to be iso-C, anteiso-C and anteiso-C. The predominant menaquinones were identified as MK-9 (H), MK-9 (H) and MK-9 (H). The major polar lipids were found to be diphosphatidylglycerol, phosphatidylinositol and phosphatidylethanolamine. The diagnostic amino acid of the cell wall peptidoglycan was determined to be meso-diaminopimelic acid. The diagnostic sugars in cell hydrolysates were determined to be glucose and ribose. On the basis of its phenotypic, phylogenetic and chemotaxonomic characteristics, strain LAM7112 (= CGMCC 4.7580 = JCM 32512) is proposed to represent the type strain of a novel species of the genus Actinoplanes, for which the name Actinoplanes solisilvae is proposed.
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http://dx.doi.org/10.1007/s00284-020-02192-zDOI Listing
November 2020

Study of upfront surgery versus neoadjuvant chemotherapy followed by interval debulking surgery for patients with stage IIIC and IV ovarian cancer, SGOG SUNNY (SOC-2) trial concept.

J Gynecol Oncol 2020 Sep;31(5):e86

Shanghai Gynecologic Oncology Group and Ovarian Cancer Program, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Two randomized phase III trials (EORTC55971 and CHORUS) showed similar progression-free and overall survival in primary or interval debulking surgery in ovarian cancer, however both studies had limitations with lower rate of complete resection and lack of surgical qualifications for participating centers. There is no consensus on whether neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) could be a preferred approach in the management of advanced epithelial ovarian cancer (EOC) in the clinical practice.

Methods: The Asian SUNNY study is an open-label, multicenter, randomized controlled, phase III trial to compare the effect of primary debulking surgery (PDS) to NACT-IDS in stages IIIC and IV EOC, fallopian tube cancer (FTC) or primary peritoneal carcinoma (PPC). The hypothesis is that PDS enhances the survivorship when compared with NACT-IDS in advanced ovarian cancer. The primary objective is to clarify the role of PDS and NACT-IDS in the treatment of advanced ovarian cancer. Surgical quality assures include at least 50% of no gross residual (NGR) in PDS group in all centers and participating centers should be national cancer centers or designed ovarian cancer section or those with the experience participating surgical trials of ovarian cancer. Any participating center should be monitored evaluating the proportions of NGR by a training set. The aim of the surgery in both arms is maximal cytoreduction. Tumor burden of the disease is evaluated by diagnostic laparoscopy or positron emission tomography/computed tomography scan. Patients assigned to PDS group will undergo upfront maximal cytoreductive surgery within 3 weeks after biopsy, followed by 6 cycles of standard adjuvant chemotherapy. Patients assigned to NACT group will undergo 3 cycles of NACT-IDS, and subsequently 3 cycles of adjuvant chemotherapy. The maximal time interval between IDS and the initiation of adjuvant chemotherapy is 8 weeks. Major inclusion criteria are pathologic confirmed stage IIIC and IV EOC, FTC or PPC; ECOG performance status of 0 to 2; ASA score of 1 to 2. Major exclusion criteria are non-epithelial tumors as well as borderline tumors; low-grade carcinoma; mucinous ovarian cancer. The sample size is 456 subjects. Primary endpoint is overall survival.

Trial Registration: ClinicalTrials.gov Identifier: NCT02859038.
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http://dx.doi.org/10.3802/jgo.2020.31.e86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440987PMC
September 2020

[Rapid screening of a hotspot variant c.609G>A in MMACHC gene by using PCR-high-resolution melting curve analysis].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Jul;37(7):759-763

Tianjin Pediatric Research Institute, Tianjin Children's Hospital, Tianjin 300134, China.

Objective: To carry out genetic testing for two families affected with cobalamin C (cblC) and establish a rapid method for the detection of a hotspot pathogenic variant c.609G>A of the MMACHC gene by using a PCR-high-resolution melting curve (PCR-HRM) method.

Methods: Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Potential variants of the MMACHC gene was analyzed by Sanger sequencing. The c.609G>A variant of the MMACHC gene was screened among 100 healthy children with the PCR-HRM method.

Results: Sanger sequencing revealed that proband 1 carried compound heterozygous variants c.394C>T and c.609G>A of the MMACHC gene, while proband 2 carried compound heterozygous variants c.482G>A and c.609G>A of the same gene. PCR-HRM analysis of the two probands and the 100 healthy children were consistent with the Sanger sequencing.

Conclusion: c.609G>A is a hotspot pathogenic variant of the MMACHC gene. The diagnosis of cblC may be rapidly attained through detection by PCR-HRM.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.07.014DOI Listing
July 2020

Identification of susceptibility variants to benign childhood epilepsy with centro-temporal spikes (BECTS) in Chinese Han population.

EBioMedicine 2020 Jul 21;57:102840. Epub 2020 Jun 21.

Guy's & St Thomas' NHS Foundation Trust and King's College London, NIHR Biomedical Research Centre, London, England United Kingdom. Electronic address:

Background: Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS) is the most common form of idiopathic epilepsy in children, accounting for up to 23% of pediatric epilepsy. The pathogenesis of BECTS is unknown, but it is thought that genetic factors play a role in susceptibility to the disease.

Methods: To investigate the role of common genetic variants in BECTS pathogenesis, a 2-stage genome-wide association study (GWAS) was performed in 1,800 Chinese Han BECTS patients, and 7,090 healthy controls. Genetic findings were used in a Mendelian Randomization study in the UK Biobank dataset to investigate the potential role of smoking in BECTS.

Findings: Definitive evidence of a role for common-variant heritability was demonstrated, with heritability of BECTS of >10% observed even with conservative disease prevalence assumptions. Although no individual locus achieved genome-wide significance, twelve loci achieved suggestive evidence of association (5 × 10
Interpretation: This study shows that BECTS risk is at least partially heritable and due to common genetic variants. Additionally, we demonstrate that BECTS risk is substantially increased by maternal smoking around birth.
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http://dx.doi.org/10.1016/j.ebiom.2020.102840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317238PMC
July 2020

Spontaneous arterial thrombosis in a patient with advanced ovarian clear cell cancer: a case report and literature review.

J Int Med Res 2020 Jun;48(6):300060520926742

Department of Gynecology & Obstetrics, Zhongshan Hospital, Fudan University, Shanghai, China.

Patients with ovarian cancer are often in a hypercoagulable state and have a high risk of venous thrombosis, including deep vein thrombosis and pulmonary embolism. However, arterial thrombosis is relatively rare in ovarian cancer. We report a case a 46-year-old woman with ovarian clear cell carcinoma who developed arterial and venous thrombosis in the lower extremities as the first manifestation. Her arterial thrombosis-related ischemic symptoms were not responsive to anticoagulant treatment of low-molecular-weight heparin, but improved after neoadjuvant chemotherapy and surgery. Therefore, we hypothesize that the optimal therapy for arterial thrombosis in ovarian cancer is treatment for the underlying disease (i.e., ovarian cancer). A thorough investigation is required to determine the relationships between arterial thrombosis and ovarian cancer and antithrombotic treatments for ovarian cancer related-arterial thrombosis.
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http://dx.doi.org/10.1177/0300060520926742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273781PMC
June 2020

[Analysis of DPYS gene variants in a child with dihydropyrimidase deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Jun;37(6):650-652

Department of Neurology, Tianjin Pediatric Hospital, Tianjin 300074, China.

Objective: To explore the genetic basis for a child with dihydropyrimidase (DHP) deficiency.

Methods: High-throughput sequencing was carried out for the child. Suspected variants were verified by using Sanger sequencing.

Results: The proband was found to carry compound heterozygous variants of the DPYS gene, namely c.1468C>T (a missense variant) and c.1339-1363del (a frameshifting variant).

Conclusion: The compound heterozygous variants of the DPYS gene probably underlie the DHP in this child. Above result has enabled genetic counseling and prenatal diagnosis for his parents.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.06.013DOI Listing
June 2020
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