Publications by authors named "Jing Jing Wang"

335 Publications

[Transformation of the domestic standard (: ) to international standard: in the perspective of the differences in clinical questions].

Zhongguo Zhen Jiu 2020 Nov;40(11):1245-9

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Through analyzing the differences in the clinical questions of : () between the domestic standard and international standard (under development), the specific issues are determined in the transformation from domestic standard to international one. Taking acupuncture practitioners as investigation object, by means of the survey, the basic information and clinical questions were investigated. The survey results show that the following aspects should be supplemented in terms of the international requirements during the development of this international : suitable patient population, applicable types of disease, the optimal intervention time of acupuncture for migraine, common methods in treatment as well as the other involved health problems. Moreover, it needs to update the key clinical questions, recommended regimens for the newly supplemented types of disease, as well as the more specified assessment on therapeutic effect. The ultimate solution of these questions relies on the quality of clinical evidence.
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http://dx.doi.org/10.13703/j.0255-2930.20200309-k0003DOI Listing
November 2020

DcTT8, a bHLH transcription factor, regulates anthocyanin biosynthesis in Dendrobium candidum.

Plant Physiol Biochem 2021 May 8;162:603-612. Epub 2021 Mar 8.

Institute of Food Science and Technology, Chinese Academy of Agricultural Science, Beijing, 100193, China; Laboratory of Quality & Safety Risk Assessment on Agro-products Processing, Ministry of Agriculture and Rural Affairs, Beijing, 100193, China. Electronic address:

Dendrobium candidum stems are used as Chinese medicine and functional food. Red stems of D. candidum are rich in anthocyanins, which attract pollinator insects, protect the plants against environmental stress, and improve human health. The regulatory mechanisms of anthocyanin biosynthesis and stem color differentiation in D. candidum are not fully understood. Using transcriptome profiling, we identified a basic helix-loop-helix transcription factor (DcTT8) involved in anthocyanin biosynthesis in D. candidum stems. Ultraperformance liquid chromatography-tandem mass spectrometry was used to determine pigment contents and compositions in red and green stems, revealing that cyanidin is responsible for the red color. DcTT8 could bind the DcF3'H and DcUFGT promoters and finely regulate DcF3'H and DcUFGT expression. Our data indicate that DcTT8 participates in anthocyanin biosynthesis and offers novel insights into the transcriptional regulation of anthocyanin biosynthesis in D. candidum.
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http://dx.doi.org/10.1016/j.plaphy.2021.03.006DOI Listing
May 2021

The corticospinal tract structure of collagen/silk fibroin scaffold implants using 3D printing promotes functional recovery after complete spinal cord transection in rats.

J Mater Sci Mater Med 2021 Mar 22;32(4):31. Epub 2021 Mar 22.

Tianjin Key Laboratory of Neurotrauma Repair, Pingjin Hospital Brain Center, Characteristic Medical Center of PAPF, Tianjin, 300162, China.

No effective treatment has been established for nerve dysfunction caused by spinal cord injury (SCI). Orderly axonal growth at the site of spinal cord transection and creation of an appropriate biological microenvironment are important for functional recovery. To axially guiding axonal growth, designing a collagen/silk fibroin scaffold fabricated with 3D printing technology (3D-C/SF) emulated the corticospinal tract. The normal collagen/silk fibroin scaffold with freeze-drying technology (C/SF) or 3D-C/SF scaffold were implanted into rats with completely transected SCI to evaluate its effect on nerve repair during an 8-week observation period. Electrophysiological analysis and locomotor performance showed that the 3D-C/SF implants contributed to significant improvements in the neurogolical function of rats compared to C/SF group. By magnetic resonance imaging, 3D-C/SF implants promoted a striking degree of axonal regeneration and connection between the proximal and distal SCI sites. Compared with C/SF group, rats with 3D-C/SF scaffold exhibited fewer lesions and disordered structures in histological analysis and more GAP43-positive profiles at the lesion site. The above results indicated that the corticospinal tract structure of 3D printing collagen/silk fibroin scaffold improved axonal regeneration and promoted orderly connections within the neural network, which could provided a promising and innovative approach for tissue repair after SCI.
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http://dx.doi.org/10.1007/s10856-021-06500-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985105PMC
March 2021

Scabies, incomplete lupus erythematosus and Henoch-Schonlein purpura.

Arch Med Sci 2021 26;17(2):564-568. Epub 2021 Feb 26.

Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, China.

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http://dx.doi.org/10.5114/aoms/131542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959089PMC
February 2021

Controlled ovarian stimulation should not be preferred for male infertility treated with intrauterine insemination: a retrospective study.

Reprod Biol Endocrinol 2021 Mar 19;19(1):45. Epub 2021 Mar 19.

Department of Gynecology and Obstetrics, Centre for Reproductive Medicine, Zhongshan City People's Hospital, No. 2, Sunwen East Road, Shiqi District, Zhongshan, 528400, Guangdong Province, China.

Background: Some studies have stated that intrauterine insemination (IUI) with controlled ovarian stimulation (COS) might increase the pregnancy rate, while others suggest that IUI in the natural cycle (NC) should be the first line of treatment. It remains unclear whether it is necessary to use COS at the same time when IUI is applied to treat isolated male factor infertility. Thus, we aimed to investigate efficacy of IUI with COS for isolated male factor infertility.

Methods: A total of 601 IUI cycles from 307 couples who sought medical care for isolated male factor infertility between January 2010 and February 2020 were divided into two groups: NC-IUI and COS-IUI. The COS-IUI group was further divided into two subgroups according to the number of pre-ovulatory follicles on the day of HCG: cycles with monofollicular development (one follicle group) and cycles with at least two pre-ovulatory follicles (≥ 2 follicles group). The IUI outcomes, including clinical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and multiple pregnancy rates were compared.

Results: The clinical pregnancy, live birth, spontaneous abortion, and ectopic pregnancy rates were comparable between the NC-IUI and COS-IUI group. Similar results were also observed among the NC-IUI, one follicle, and ≥ 2 follicles groups. However, with respect to the multiple pregnancy rate, a trend toward higher multiple pregnancy rate was observed in the COS-IUI group compared to the NC-IUI group (8.7% vs. 0, P = 0.091), and a significant difference was found between the NC-IUI and ≥ 2 follicles group (0 vs. 16.7%, P = 0.033).

Conclusion: In COS cycles, especially in those with at least two pre-ovulatory follicles, the multiple pregnancy rate increased without a substantial gain in overall pregnancy rate; thus, COS should not be preferred in IUI for isolated male factor infertility. If COS is required, one stimulated follicle and one healthy baby should be the goal considering the safety of both mothers and foetuses.
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http://dx.doi.org/10.1186/s12958-021-00730-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977560PMC
March 2021

Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review.

World J Gastroenterol 2021 Mar;27(9):886-907

Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.

Background: Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.

Aim: To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.

Methods: We searched PubMed/MEDLINE, Embase, and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.

Results: A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6 μg/mL in IBD. Blood concentration of infliximab reaching 5.0-12.7 μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease. Blood concentration of adalimumab reaching 7.2-16.2 μg/mL or more could predict mucosal healing in IBD. The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8 μg/mL in perianal fistulizing Crohn's disease. Blood concentration of vedolizumab surpassing 25.0 μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 μg/mL.

Conclusion: Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies, whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.
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http://dx.doi.org/10.3748/wjg.v27.i9.886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941861PMC
March 2021

Effects of the curcumin-mediated photodynamic inactivation on the quality of cooked oysters with Vibrio parahaemolyticus during storage at different temperature.

Int J Food Microbiol 2021 May 10;345:109152. Epub 2021 Mar 10.

Department of Food Science, Foshan University, Foshan 528000, China; College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China. Electronic address:

Photodynamic inactivation (PDI) is a promising method with multiple targets to inactivate bacteria on food using visible light. Inactivation potency of the curcumin-mediated blue light-emitting diode (LED) PDI against the pathogen Vibrio parahaemolyticus on cooked oysters and its effects on the storage quality were investigated by the microbiological, physical, chemical and histological methods during storage at 4 °C, 10 °C and 25 °C. Results showed that the PDI treatment obviously inhibited the recovery of V. parahaemolyticus on oysters during storage, and the maximal difference attained >1.0 Log CFU/g (> 90%) compared to control stored at 10 °C and 25 °C. Meanwhile, it displayed a potent ability (p < 0.05) to restrain the decrease of pH values, reduce the production of total volatile basic nitrogen (TVB-N), suppress the lipids oxidation, as well as retard the changes of color difference of the oysters. In addition, the PDI effectively maintained the integrity and initial attachments of muscle fibers, and hence decreased the loss of water in myofibrillar space and the texture softening of oysters during storage. On this basis, this study facilitates the understanding of the potency of bacterial inactivation and food preservation of PDI, and hence pave the way for its application in food industry.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109152DOI Listing
May 2021

A set of RT-PCR assays for detection of all known avian paramyxoviruses and application in surveillance of avian paramyxoviruses in China.

PeerJ 2021 4;9:e10748. Epub 2021 Mar 4.

Laboratory for Avian Disease Surveillance (OIE Reference Laboratory for Newcastle Disease), China Animal Health and Epidemiology Center, Qingdao, China.

Background: Avian paramyxoviruses (APMVs), also termed avian avulaviruses, are of a vast diversity and great significance in poultry. Detection of all known APMVs is challenging, and distribution of APMVs have not been well investigated.

Methods: A set of reverse transcription polymerase chain reaction (RT-PCR) assays for detection of all known APMVs were established using degenerate primers targeting the viral polymerase L gene. The assays were preliminarily evaluated using in-vitro transcribed double-stranded RNA controls and 24 known viruses, and then they were employed to detect 4,346 avian samples collected from 11 provinces.

Results: The assays could detect 20-200 copies of the double-stranded RNA controls, and detected correctly the 24 known viruses. Of the 4,346 avian samples detected using the assays, 72 samples were found positive. Of the 72 positives, 70 were confirmed through sequencing, indicating the assays were specific for APMVs. The 4,346 samples were also detected using a reported RT-PCR assay, and the results showed this RT-PCR assay was less sensitive than the assays reported here. Of the 70 confirmed positives, 40 were class I Newcastle disease virus (NDV or APMV-1) and 27 were class II NDV from poultry including chickens, ducks, geese, and pigeons, and three were APMV-2 from parrots. The surveillance identified APMV-2 in parrots for the first time, and revealed that prevalence of NDVs in live poultry markets was higher than that in poultry farms. The surveillance also suggested that class I NDVs in chickens could be as prevalent as in ducks, and class II NDVs in ducks could be more prevalent than in chickens, and class II NDVs could be more prevalent than class I NDVs in ducks. Altogether, we developed a set of specific and sensitive RT-PCR assays for detection of all known APMVs, and conducted a large-scale surveillance using the assays which shed novel insights into APMV epidemiology.
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http://dx.doi.org/10.7717/peerj.10748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937338PMC
March 2021

Combining NMR-Based Metabolic Profiling and Genome Mining for the Accelerated Discovery of Archangiumide, an Allenic Macrolide from the Myxobacterium SDU8.

Org Lett 2021 Mar 10;23(6):2114-2119. Epub 2021 Mar 10.

State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, 266237 Qingdao, P.R. China.

An unprecedented 19-membered allenic macrolide archangiumide () was discovered from the myxobacterium SDU8 by integrating NMR-based metabolic profiling and genome mining. Its biosynthesis pathway was proposed based on the architectural analysis of the encoding -AT PKS genes and validated by isotope labeling. The methodology of combing 2D NMR-based metabolic profiling and bioinformatics-aided structure prediction, as exemplified by this study, is anticipated to improve discovery efficiency of a broader range of microbial "dark matter".
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http://dx.doi.org/10.1021/acs.orglett.1c00265DOI Listing
March 2021

Recent advances in total syntheses of natural products containing the benzocycloheptane motif.

Nat Prod Rep 2021 Mar 2. Epub 2021 Mar 2.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.

Covering: 2010 to 2020Benzocycloheptane is a fundamental and unique structural motif found in pharmaceuticals and natural products. The total syntheses of natural products bearing the benzocycloheptane subunit are challenging and there are only a few efficient approaches to access benzocycloheptane. Thus, new methods and innovative strategies for preparing such natural products need to be developed. In this review, recent progress in the total syntheses of natural products bearing the benzocycloheptane motif is presented, and key transformations for the construction of benzocycloheptane are highlighted. This review provides a useful guide for those engaged in the syntheses of natural products containing the benzocycloheptane motif.
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http://dx.doi.org/10.1039/d1np00003aDOI Listing
March 2021

Research progress on hosts and carriers, prevalence, virulence of infectious hypodermal and hematopoietic necrosis virus (IHHNV).

J Invertebr Pathol 2021 Feb 14:107556. Epub 2021 Feb 14.

School of Agriculture, Ludong University, Yantai, PR China. Electronic address:

Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is one of the major viral pathogens of penaeid shrimp and it has spread worldwide. IHHNV causes substantial economic loss to the shrimp farming industry and has been listed as a notifiable crustacean disease pathogen by the World Organization for Animal Health (OIE). In this paper, we reviewed studies on the hosts and carriers, prevalence, genotypes and virulence of IHHNV. The pathogenesis mechanisms of IHHNV and the viral interference between IHHNV and white spot syndrome virus (WSSV) were also discussed. The mechanism of IHHNV infection and its virulence difference in different hosts and different developmental stages have not been fully studied yet. The mechanisms underlying viral interference between IHHNV and WSSV are not yet fully understood. Further studies need perform to elucidate the precise molecular mechanisms underlying IHHNV infection and to apply the insights gained from such studies for the effective control and prevention of IHHNV disease.
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http://dx.doi.org/10.1016/j.jip.2021.107556DOI Listing
February 2021

Role of the IL-33/ST2 axis in cigarette smoke-induced airways remodelling in chronic obstructive pulmonary disease.

Thorax 2021 Feb 15. Epub 2021 Feb 15.

Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China

Background: Efficient therapy and potential prophylaxis are confounded by current ignorance of the pathogenesis of airway remodelling and blockade in COPD.

Objective: To explore the role of the IL-33/ST2 axis in cigarette smoke (CS) exposure-induced airways remodelling.

Methods: C57BL/6, BALB/c and mice exposed to CS were used to establish an animal surrogate of COPD (air-exposed=5~8, CS-exposed=6~12). Hallmarks of remodelling were measured in mice. Cigarette smoke extract (CSE)-induced proliferation and protein production in vitro by fibroblasts in the presence of anti-interleukin-33 (anti-IL-33) or hST2 antibodies were measured. Expression of IL-33 and ST2 and other remodelling hallmarks were measured, respectively, in bronchoalveolar lavage fluid (BALF) (controls=20, COPD=20), serum (controls=59, COPD=90) and lung tissue sections (controls=11, COPD=7) from patients with COPD and controls.

Results: Wild-type mice exposed to CS elevated expression of hallmarks of tissue remodelling in the lungs and also in the heart, spleen and kidneys, which were significantly abrogated in the mice. Fibroblasts exposed to CSE, compared with control, exhibited early cellular translocation of IL-33, accompanied by proliferation and elevated protein synthesis, all inhabitable by blockade of IL-33/ST2 signalling. Expression of IL-33 and ST2 and hallmarks of tissue remodelling were significantly and proportionally elevated in BALF, serum and tissue samples from patients with COPD.

Conclusions: Exposure to CS induces remodelling changes in multiple organs. The data support the hypothesis that CS-induced lung collagen deposition is at least partly a result of CS-induced IL-33 translocation and release from local fibroblasts.
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http://dx.doi.org/10.1136/thoraxjnl-2020-214712DOI Listing
February 2021

[Analysis on international demand investigation for technical specification of acupuncture- moxibustionthe and its general rules of drafting].

Zhongguo Zhen Jiu 2021 Jan;41(1):89-93

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.

The electronic questionnaire was adopted to survey the international demand on - ( for short) to explore the potential problems during the application and provide the evidence for the development of international standard of . A total of 102 valid questionnaires were collected from 18 countries and regions. The priority of the demand for international standard on the technical specification of acupuncture-moxibustion is filiform needle, moxibustion, electroacupuncture, cupping, auricular acupuncture, scalp acupuncture and scraping. One hundred experts (98.04%) at home and abroad believe the necessity of the international standard development of . The awareness rate of the existing national standard of is 71.57% and the foreign experts think that its expression may be "unclear" and the domestic experts think it may be "lack of practicability". The domestic experts hope to highlight the commonness in the scope of the international standard of and the foreign experts hope to retain more individuality. Regarding the specific questions during the technique manipulations of acupuncture-moxibustion, there are the big differences in "relevant terminology" "preoperative preparation" and "adverse reaction and contraindications" at home and abroad. In order to improve the international compatibility and applicability, it is necessary to give full consideration to the needs of different countries in the development of international standard of and balance as far as possible between refining "common problems" and satisfying "individual needs".
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http://dx.doi.org/10.13703/j.0255-2930.20200601-k0002DOI Listing
January 2021

Effects of Different Component Contents of Colistin Methanesulfonate on the Pharmacokinetics of Prodrug and Formed Colistin in Human.

Pharm Res 2021 Jan 26;38(1):79-87. Epub 2021 Jan 26.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Purposes: To evaluate the effects of component contents in different colistin methanesulfonate (CMS) formulas on their clinical pharmacokinetics of the prodrug CMS and the formed colistin.

Methods: Two CMS formulas (CTTQ and Parkedale) were investigated in a single dose, randomized, open-label, crossover study conducted in 18 healthy Chinese subjects. Both CMS formulas met the requirements of European Pharmacopoeia 9.2 with 12.1% difference in the two major active components (CMS A and CMS B). The PK parameters after a single intravenous infusion of CMS at 2.5 mg/kg were calculated and the steady-state plasma colistin concentrations (C) following multiple dosing, once every 12 h for 7 days, were simulated with the non-compartment model.

Results: The systemic exposure (AUC) of CMS were 59.49 ± 5.90 h·μg/mL and 51.09 ± 4.70 h·μg/mL, and the AUC of colistin were 15.39 ± 2.63 h·μg/mL and 12.36 ± 2.10 h·μg/mL for CTTQ and Parkedale, respectively. The ratios (90% CI) of geometric mean of AUC of CTTQ to Parkedale were 116.38% (112.95%, 119.91%) and 124.49% (120.76%, 128.35%) for CMS and colistin, respectively. The predicted C (95% CI) were 0.92 (0.85, 0.99) μg/mL and 0.74 (0.69, 0.79) μg/mL for CTTQ and Parkedale, respectively.

Conclusion: The difference in component content in the two CMS formulas had a significant (P < 0.001) impact on the systemic exposure of colistin in human, thus, warranted essential considerations in clinical applications.
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http://dx.doi.org/10.1007/s11095-021-02991-4DOI Listing
January 2021

A systematic review of synthetic tyrosinase inhibitors and their structure-activity relationship.

Crit Rev Food Sci Nutr 2021 Jan 18:1-42. Epub 2021 Jan 18.

College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.

Tyrosinase is a copper-containing oxidation enzyme, which is responsible for the production of melanin. This enzyme is widely distributed in microorganisms, animals and plants, and plays an essential role in undesirable browning of fruits and vegetables, antibiotic resistance, skin pigment formation, sclerotization of cuticle, neurodegeneration, etc. Hence, it has been recognized as a therapeutic target for the development of antibrowning agents, antibacterial agents, skin-whitening agents, insecticides, and other therapeutic agents. With great potential application in food, agricultural, cosmetic and pharmaceutical industries, a large number of synthetic tyrosinase inhibitors have been widely reported in recent years. In this review, we systematically summarized the advances of synthetic tyrosinase inhibitors in the literatures, including their inhibitory activity, cytotoxicity, structure-activity relationship (SAR), inhibition kinetics, and interaction mechanisms with the enzyme. The collected information is expected to provide a rational guidance and effective strategy to develop novel, potent and safe tyrosinase inhibitors for better practical applications in the future.
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http://dx.doi.org/10.1080/10408398.2021.1871724DOI Listing
January 2021

Clinical and survival analysis of nasopharyngeal carcinoma with consistently negative Epstein-Barr virus DNA.

Head Neck 2021 May 9;43(5):1465-1475. Epub 2021 Jan 9.

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

Background: To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein-Barr virus (EBV) DNA level.

Methods: Propensity score matching (PSM) method was used to create well-balanced cohorts. Kaplan-Meier method and Cox proportional hazards models were performed to conduct survival analysis.

Results: Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p < .001; p = .015). And patients with consistently negative EBV level were significantly associated with preferable 3-year DFS (95.0% vs. 84.4%, p = .004), DMFS (98.3% vs. 89.4%, p = .009), and OS (100% vs. 97.6%, p = .004).

Conclusions: NPC patients with consistently negative EBV DNA level performed an earlier clinical stage and negative EBV DNA level was related to preferable survival outcomes.
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http://dx.doi.org/10.1002/hed.26608DOI Listing
May 2021

Identification of Potential Therapeutic Targets of Alzheimer's Disease By Weighted Gene Co-Expression Network Analysis.

Chin Med Sci J 2020 Dec;35(4):330-341

Pharmacy School, Guangxi University of Chinese Medicine, Nanning 530200, China.

Objective Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of the disease mostly remains unearthed, thereby challenging drug development for AD. This study aims to screen high throughput gene expression data using weighted co-expression network analysis (WGCNA) to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus (GEO) database. Normalization, quality control, filtration, and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules. Furthermore, the correlation coefficients between the modules and clinical traits were computed to identify the key modules. Gene ontology and pathway enrichment analyses were performed on the key module genes. The STRING database was used to construct the protein-protein interaction (PPI) networks, which were further analyzed by Cytoscape app (MCODE). Finally, validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules, among which 6 modules were identified as the key module relating to AD occurrence. These key modules are primarily involved in chemical synaptic transmission (GO:0007268), the tricarboxylic acid (TCA) cycle and respiratory electron transport (R-HSA-1428517). , , , , , were found as the hub genes and their expression were validated by external datasets.Conclusions Through modules co-expression network analyses and PPI network analyses, we identified the hub genes of AD, including , , , , and . Among them, three hub genes (, , ) might contribute to AD pathogenesis through pathway of TCA cycle.
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http://dx.doi.org/10.24920/003695DOI Listing
December 2020

Multifunctional TiCT MXene Composite Hydrogels with Strain Sensitivity toward Absorption-Dominated Electromagnetic-Interference Shielding.

ACS Nano 2021 Jan 5;15(1):1465-1474. Epub 2021 Jan 5.

Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) and Advanced Materials Bio-Engineering Research Centre (AMBER), Trinity College Dublin, Dublin, Dublin 2, Ireland.

The fast development of terahertz technologies demands high-performance electromagnetic interference (EMI) shielding materials to create safe electromagnetic environments. Despite tremendous breakthroughs in achieving superb shielding efficiency (SE), conventional shielding materials have high reflectivity and cannot be re-edited or recycled once formed, resulting in detrimental secondary electromagnetic pollution and poor adaptability. Herein, a hydrogel-type shielding material incorporating MXene and poly(acrylic acid) is fabricated through a biomineralization-inspired assembly route. The composite hydrogel exhibits excellent stretchability and recyclability, favorable shape adaptability and adhesiveness, and fast self-healing capability, demonstrating great application flexibility and reliability. More interestingly, the shielding performance of the hydrogel shows absorption-dominated feature due to the combination of the porous structure, moderate conductivity, and internal water-rich environment. High EMI SE of 45.3 dB and broad effective absorption bandwidth (0.2-2.0 THz) with excellent refection loss of 23.2 dB can be simultaneously achieved in an extremely thin hydrogel (0.13 mm). Furthermore, such hydrogel demonstrates sensitive deformation responses and can be used as an on-skin sensor. This work provides not only an alternative strategy for designing next-generation EMI shielding material but also a highly efficient and convenient method for fabricating MXene composite on macroscopic scales.
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http://dx.doi.org/10.1021/acsnano.0c08830DOI Listing
January 2021

Modulation of Metal Halide Structural Units for Light Emission.

Acc Chem Res 2021 Jan 4;54(2):441-451. Epub 2021 Jan 4.

Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China.

ConspectusWith the development of solid-state lighting technology, efficient light sources that combine high brightness, wide range, and good stability are in high demand for next-generation lighting and displays. Metal halides are emerging as promising luminescent materials due to their versatility for desirable light emission manipulations. This is because the optical activity of the metal halide material depends on the metal halide structural unit and the organic ions or coordinated organic ligands. The different assembly of metal halide units and organic parts can enable versatile light emissions, such as lead halide perovskites (LHPs) and copper halide-organic hybrids. Impressively, the external quantum efficiency of the LHP based light-emitting diodes (LEDs) has improved significantly from 0.1% to over 20% in just five years. With this great progress, the structural lability and toxicity of the LHPs are now the critical issues that need to be addressed for practical applications. These issues are mainly rooted in the intrinsic lead composition and low formation energy crystal structure of the widely adopted LHPs. Thus, the modulation of the structure and composition of the basic metal halide structural units is considered a rational strategy to address these issues.In this Account, we will present a general material design using metal halide structural units as basic building blocks to build up metal halide luminescent materials for solid-state lighting devices. Following this route, we will emphasize the modulation of metal halide structural units to tackle the existing challenges in lead halides, including the instability of crystalline structure, ion migration, and the presence of toxic lead. Considering basic components in structural units, we will highlight ionic engineering in LHPs via ion doping, substitution, and modification to enhance the crystal structural stability and suppress ion migration. To replace toxic lead, we will introduce recent advances in the modulation of lead-free halide structural units by active ion doping and organic ligand coordination to fabricate highly luminescent materials. Finally, we will present future strategies of metal halide structural unit modulation for solid-state light emissions. We hope this Account will provide new insights for designing metal halide materials from the viewpoint of the modulation of the basic building blocks and inspire future studies of advanced metal halide materials for solid-state light emitting applications.
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http://dx.doi.org/10.1021/acs.accounts.0c00707DOI Listing
January 2021

Tumor Mutation Burden, Immune Cell Infiltration, and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer.

Int J Med Sci 2021 1;18(1):226-238. Epub 2021 Jan 1.

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors. This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis. Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. , , and were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635. Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.
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http://dx.doi.org/10.7150/ijms.51064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738958PMC
January 2021

Lycium barbarum Polysaccharide Antagonizes LPS-Induced Inflammation by Altering the Glycolysis and Differentiation of Macrophages by Triggering the Degradation of PKM2.

Biol Pharm Bull 2021 Mar 26;44(3):379-388. Epub 2020 Dec 26.

Intensive Care Unit (ICU), Department of Critical Care Unit, Ningxia Third Hospital.

Lipopolysaccharide (LPS)-induced inflammation is the leading cause of multiple organ failure in sepsis. Pyruvate kinase 2 (PKM2) is a protein kinase and transcriptional coactivator that plays an important role in glycolysis. Recent studies have confirmed that glycolysis maintains the M1 differentiation and induces immune activation in macrophages. Lycium barbarum polysaccharide (LBP), the main bioactive component of Chinese wolfberry, suppresses glycolysis and inflammation. Here, RAW264.7 macrophages were treated with LBP for evaluating its effects against LPS-induced inflammation. The differentiation of M1/M2 macrophages was assessed by flow cytometry for assessing the cell surface markers, CD86 and CD206. The enrichment of hypoxia inducible factor (HIF)-1α and ubiquitin in the PKM2 protein complex was determined by co-immunoprecipitation. LBP suppressed LPS-induced glycolysis, differentiation of M1 macrophages, and the production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and high mobility group (HMG) 1 proteins. The suppressive effects of LBP were similar to those of PKM2 knockdown, but were abolished by the overexpression of PKM2. LPS elevated the mRNA and protein levels of PKM2. LBP reduced the LPS-induced expression of PKM2 protein, but had no effects on the expression of PKM2 mRNA. LPS inhibited the ubiquitination of PKM2, probably by downregulating the expression of ubiquitin ligases, including Nedd4L, Nedd4, and Gnb2. LBP interfered with the inhibition of PKM2 ubiquitination by upregulating the expression of Nedd4L, Nedd4, and Gnb2. In conclusion, LBP suppressed the LPS-induced inflammation by altering glycolysis and the M1 differentiation of macrophages. The effects of LBP were mediated by the downregulation of PKM2 via enhanced ubiquitination.
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http://dx.doi.org/10.1248/bpb.b20-00752DOI Listing
March 2021

Development of a prognostic model of glioma based on immune-related genes.

Oncol Lett 2021 Feb 15;21(2):116. Epub 2020 Dec 15.

Department of Neurosurgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China.

Glioma is the most common type of primary brain cancer, and the prognosis of most patients with glioma, and particularly that of patients with glioblastoma, is poor. Tumor immunity serves an important role in the development of glioma. However, immunotherapy for glioma has not been completely successful, and thus, comprehensive examination of the immune-related genes (IRGs) of glioma is required. In the present study, differentially expressed genes (DEGs) and differentially expressed IRGs (DEIRGs) were identified using the edgeR package. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used for functional enrichment analysis of DEIRGs. Survival-associated IRGs were selected via univariate Cox regression analysis. A The Cancer Genome Atlas prognostic model and GSE43378 validation model were established using lasso-penalized Cox regression analysis. Based on the median risk score value, patients were divided into high-risk and low-risk groups for clinical analysis. Receiver operating characteristic curve and nomogram analyses were used to assess the accuracy of the models. Reverse transcription-quantitative PCR was performed to measure the expression levels of relevant genes, such as cyclin-dependent kinase 4 (CDK4), interleukin 24 (IL24), NADPH oxidase 4 (NOX4), bone morphogenetic protein 2 (BMP2) and baculoviral IAP repeat containing 5 (BIRC5). A total of 3,238 DEGs, including 1,950 upregulated and 1,288 downregulated DEGs, and 97 DEIRGs, including 60 upregulated and 37 downregulated DEIRGs, were identified. 'Neuroactive ligand-receptor interaction' and 'Cytokine-cytokine receptor interaction' were the most significantly enriched pathways according to KEGG pathway analysis. A prognostic model and a validation prognostic model were created for glioma, including 15 survival-associated IRGs (FCER1G, NOX4, TRIM5, SOCS1, APOBEC3C, BIRC5, VIM, TNC, BMP2, CMTM3, IL24, JAG1, CALCRL, HNF4G and CDK4). Furthermore, multivariate Cox regression analysis results suggested that age, high WHO Grade by histopathology, wild type isocitrate dehydrogenase 1 and high risk score were independently associated with poor overall survival. The infiltration of B cells, CD8 T cells, dendritic cells, macrophages and neutrophils was positively associated with the prognostic risk score. In the present study, several clinically significant survival-associated IRGs were identified, and a prognosis evaluation model of glioma was established.
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http://dx.doi.org/10.3892/ol.2020.12377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751470PMC
February 2021

Large-Scale and Flexible Optical Synapses for Neuromorphic Computing and Integrated Visible Information Sensing Memory Processing.

ACS Nano 2021 01 29;15(1):1497-1508. Epub 2020 Dec 29.

Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Optoelectronic synapses integrating synaptic and optical-sensing functions exhibit large advantages in neuromorphic computing for visual information processing and complex learning, recognition, and memory in an energy-efficient way. However, electric stimulation is still essential for existing optoelectronic synapses to realize bidirectional weight-updating, restricting the processing speed, bandwidth, and integration density of the devices. Herein, a two-terminal optical synapse based on a wafer-scale pyrenyl graphdiyne/graphene/PbS quantum dot heterostructure is proposed that can emulate both the excitatory and inhibitory synaptic behaviors in an optical pathway. The simple device architecture and low-dimensional features of the heterostructure endow the optical synapse with robust flexibility for wearable electronics. This optical synapse features a linear and symmetric conductance-update trajectory with numerous conductance states and low noise, which facilitates the demonstration of accurate and effective pattern recognition with a strong fault-tolerant capability even at bending states. A series of logic functions and associative learning capabilities have been demonstrated by the optical synapses in optical pathways, significantly enhancing the information processing capability for neuromorphic computing. Moreover, an integrated visible information sensing memory processing system based on the optical synapse array is constructed to perform real-time detection, image memorization, and distinction tasks. This work is an important step toward the development of optogenetics-inspired neuromorphic computing and adaptive parallel processing networks for wearable electronics.
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http://dx.doi.org/10.1021/acsnano.0c08921DOI Listing
January 2021

Localized amyloidosis affecting the lacrimal sac managed by endoscopic surgery: A case report.

World J Clin Cases 2020 Nov;8(22):5684-5689

Department of Otorhinolaryngology, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai 200031, China.

Background: Here we present a rare case of localized amyloidosis involving the nasolacrimal duct and lacrimal sac which was managed by endoscopic surgery.

Case Summary: A 50-year-old man whose medical history included bilateral ventricular fold and vocal cord amyloidosis complained of bilateral epiphora. Magnetic resonance imaging revealed a neoplasm within the nasolacrimal sac. Characteristic positivity for Congo red staining and birefringence under a polarized microscope proved the diagnosis of amyloidosis. Dacryocystorhinostomy an endoscope obtained a favorable result. A one-year follow-up found no recurrence.

Conclusion: There are few reports on amyloidosis involving the lacrimal outflow system, and management and outcome are not clear. Endoscopic dacryocystorhinostomy can be a choice to relieve symptoms. Regular follow-up and monitoring of systemic diseases are highly recommended.
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http://dx.doi.org/10.12998/wjcc.v8.i22.5684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716319PMC
November 2020

Effects of compound growth regulators on the anatomy of Jujube Leaf and Fruit.

Saudi J Biol Sci 2020 Dec 13;27(12):3660-3668. Epub 2020 Aug 13.

Institute of Forestry and Horticulture, Xinjiang Academy of Agricultural Sciences, Shihezi 832000, China.

Effects of three compound growth regulators formulated with hypersensitivity protein, spermidine, salicylic acid and DA-6 (diethyl aminoethanol hexanoate) were tested on Xinjiang Jun Jujube. The doses of compound growth regulators were named as A (Hypersensitivity protein + spermidine + salicylic acid at the rate of 30 mg/L, 0.1 mmol/L and 0.25 mmol/L, respectively), B (Hypersensitive protein + spermidine + DA-6 at the rate of 30 mg/L, 0.1 mmol/L and 30 mg/L, respectively) and C (Spermidine + salicylic acid + DA-6 at the rate of 0.1 mmol/L, 0.25 mmol/L and 30 mg/L, respectively) versus a control group CK (contained only water). Fruit anatomical structures were compared after spraying. The results indicated that after spraying, the thickness of the upper and lower epidermal cells and the stratum corneum were increased. However, the upper epidermal stratum corneum became significantly thicker than the lower epidermis. Spraying with A improved the thickness of upper and lower epidermal cells, stratum corneum, the central vein and mesophyll. The cumulative effects of all these changes in leaf and fruit anatomical structures provided the resistance of the experimental fruit plant to stress. While the B and C regulators had inhibitory effects. So, the results obtained after spraying A category were beneficial to improve the stress resistance of the fruits. The length and cell area of pericarp and sarcocarp cells in the treatment groups were not changed significantly. But the length, number of sarcocarp cells and number of gaps were lower than those in the CK. This study can provide new measures for improving plant resistance in jujube production.
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http://dx.doi.org/10.1016/j.sjbs.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714976PMC
December 2020

Performance evaluation of two fundus oculi angiographic imaging system: Optos 200Tx and Heidelberg Spectralis.

Exp Ther Med 2021 Jan 5;21(1):19. Epub 2020 Nov 5.

Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.

The present study aimed to compare the imaging performance of two ultra-wide-field fluorescein angiography imaging systems, namely the OptosOptomap 200Tx (Optos 200Tx) and the Heidelberg Spectralis (Spectralis). A total of 18 patients (36 eyes) underwent angiography using the two systems at the Department of Ophthalmology, Beijing Friendship Hospital (Beijing, China) between January and June 2017. The images were obtained as a single shot centered on the macula. The total area and area within each of four visualized quadrants were calculated and compared. The averages of the total and individual quadrant area captured by the Optos 200Tx were all larger than those obtained with the Spectralis (P<0.05). For pair-wise comparison, the circular area centered on the macula (radius of 10 and 15 mm) was displayed: Optos 200Tx 10 mm (295.57 mm) < Spectralis (520.11 mm) < Optos 200Tx 15 mm (596.45 mm) < Optos 200Tx (804.36 mm) (P<0.01). The differences of each of the four quadrant areas were statistically significant between the two systems (P<0.05). The mean size of the areas was in the following order: Inferior < temporal < superior < nasal for the Optos 200Tx, and inferior < temporal < nasal < superior for the Spectralis. Further comparison of the four-quadrant area indicated that the inferior quadrant of the Optos 200Tx was smaller than the other three quadrants (P<0.01) and the inferior quadrant of the Spectralis was smaller than the superior quadrant (P<0.01). The total retinal area and the retinal area of each quadrant captured by the Optos 200Tx were larger than those captured with the Spectralis. The total retinal area captured with the Optos 200Tx was able to cover the mid-peripheral area and part of the far-peripheral area of the retina, whereas the Spectralis only covered the mid-peripheral area.
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http://dx.doi.org/10.3892/etm.2020.9451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678619PMC
January 2021

VEGF-PLGA controlled-release microspheres enhanced angiogenesis in encephalomyosynangiosis-based chronic cerebral hypoperfusion.

J Clin Neurosci 2020 Nov 5;81:122-132. Epub 2020 Oct 5.

Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China. Electronic address:

Treatments enhancing angiogenesis for chronic cerebral hypoperfusion (CCH) are still in the research stage. Although encephalomyosynangiosis (EMS) is a common indirect anastomosis for the treatment of CCH, the effectiveness to promote angiogenesis is not satisfactory. Vascular endothelial growth factors (VEGF) is a cytokine found to specifically act directly on vascular endothelial cells, promote neovascularization, and enhance capillary permeability. However, the short half life and unstable property of VEGF underlies the need to explore available delivery system. In this study, poly (lactide-co-glycolide) (PLGA) was used to prepare VEGF controlled-release microspheres. In vitro and in vivo analysis of release kinetics showed that the microspheres could release VEGF continuously within 30 days. Then, modified chronic cerebral hypoperfusion rat model was established by ligation of bilateral internal carotid artery and one vertebral artery. At 14 days after ischemia, the EMS and the VEGF microspheres injection were performed. At 30 days after the injection, the result of Morris water maze displayed that combinating VEGF microspheres and EMS significantly ameliorated cognitive deficit after ischemia. We observed that combinating VEGF microspheres and EMS could further significantly increase cerebral blood flow. We speculated that this enhancement of cerebral blood flow was attributed to more angiogenesis induced by combination of VEGF microspheres and EMS, which verified by more collateral circulation with cerebral angiography and higher expression of CD31 or α-SMA. Our study demonstrated that combinating VEGF-PLGA controlled-release microspheres could significantly promote angiogenesis in EMS-based CCH rats model, providing new ideas for clinical treatment of CCH.
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http://dx.doi.org/10.1016/j.jocn.2020.09.023DOI Listing
November 2020

Synthesis and structure-activity relationship of coumarins as potent Mcl-1 inhibitors for cancer treatment.

Bioorg Med Chem 2021 Jan 7;29:115851. Epub 2020 Nov 7.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Myeloid cell leukemia-1 (Mcl-1) is a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to their resistance to current chemotherapeutics. In this study, more than thirty coumarin derivatives with different substituents were designed and synthesized, and their Mcl-1 inhibitory activities evaluated using a fluorescence polarization-based binding assay. The results showed that the catechol group was a key constituent for Mcl-1 inhibitory activity of the coumarins, and methylation of the catechol group led to decreased inhibitory activity. The introduction of a hydrophobic electron-withdrawing group at the C-4 position of 6,7-dihydroxycoumarin, enhanced Mcl-1 inhibitory capacity, and a hydrophilic group in this position was unbeneficial to the inhibitory potency. In addition, the introduction of a nitrogen-containing group to the C-5 or C-8 position, which allowed an intramolecular hydrogen bond, was also unfavorable for Mcl-1 inhibition. Among all coumarins tested, 4-trifluoromethyl-6,7-dihydroxycoumarin (Cpd 4) displayed the most potent inhibitory activity towards Mcl-1 (K = 0.21 ± 0.02 μM, IC = 1.21 ± 0.56 μM, respectively), for which the beneficial effect on taxol resistance was also validated in A549 cells. A strong interaction between Cpd 4 and Mcl-1 in docking simulations further supported the observed potent Mcl-1 inhibition ability of Cpd 4. 3D-QSAR analysis of all tested coumarin derivatives further provides new insights into the relationships linking the inhibitory effects on Mcl-1 and the steric-electrostatic properties of coumarins. These findings could be of great value for medicinal chemists for the design and development of more potent Mcl-1 inhibitors for biomedical applications.
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http://dx.doi.org/10.1016/j.bmc.2020.115851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855844PMC
January 2021

Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study.

Lancet Neurol 2021 01 16;20(1):49-59. Epub 2020 Nov 16.

Centro Hospitalar Universitário do Porto, Porto, Portugal.

Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy.

Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261.

Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups.

Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

Funding: Alnylam Pharmaceuticals.
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http://dx.doi.org/10.1016/S1474-4422(20)30368-9DOI Listing
January 2021

Identification of immune-related genes as prognostic factors in bladder cancer.

Sci Rep 2020 11 12;10(1):19695. Epub 2020 Nov 12.

Department of General Practice, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People's Republic of China.

Bladder cancer is one of the most common cancers worldwide. The immune response and immune cell infiltration play crucial roles in tumour progression. Immunotherapy has delivered breakthrough achievements in the past decade in bladder cancer. Differentially expressed genes and immune-related genes (DEIRGs) were identified by using the edgeR package. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for functional enrichment analysis of DEIRGs. Survival-associated IRGs were identified by univariate Cox regression analysis. A prognostic model was established by univariate COX regression analysis, and verified by a validation prognostic model based on the GEO database. Patients were divided into high-risk and low-risk groups based on the median risk score value for immune cell infiltration and clinicopathological analyses. A regulatory network of survival-associated IRGs and potential transcription factors was constructed to investigate the potential regulatory mechanisms of survival-associated IRGs. Nomogram and ROC curve to verify the accuracy of the model. Quantitative real-time PCR was performed to validate the expression of relevant key genes in the prognostic model. A total of 259 differentially expressed IRGs were identified in the present study. KEGG pathway analysis of IRGs showed that the "cytokine-cytokine receptor interaction" pathway was the most significantly enriched pathway. Thirteen survival-associated IRGs were selected to establish a prognostic index for bladder cancer. In both TCGA prognostic model and GEO validation model, patients with high riskscore had worse prognosis compared to low riskscore group. A high infiltration level of macrophages was observed in high-risk patients. OGN, ELN, ANXA6, ILK and TGFB3 were identified as hub survival-associated IRGs in the network. EBF1, WWTR1, GATA6, MYH11, and MEF2C were involved in the transcriptional regulation of these survival-associated hub IRGs. The present study identified several survival-associated IRGs of clinical significance and established a prognostic index for bladder cancer outcome evaluation for the first time.
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http://dx.doi.org/10.1038/s41598-020-76688-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661532PMC
November 2020