Publications by authors named "Zhuping Xu"

8 Publications

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Eye pain and blurred vision as main complaints in a new case with MDPL syndrome.

Eur J Ophthalmol 2021 Apr 16:11206721211009179. Epub 2021 Apr 16.

Department of ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Introduction: We report a novel phenotype of mandibular hypoplasia, deafness, and progeroid features with lipodystrophy (MDPL) syndrome with mutation in a Chinese girl.

Case Description: Diabetic retinopathy was detected as the primary manifestation in a Chinese girl with MDPL syndrome carrying a known mutation (c.1812_1814delCTC, p.Ser605del). Typical characteristics of the syndrome including mandibular hypoplasia, deafness, progeroid features, and diabetes were detected after comprehensive examinations. The patient suffered from blurred vision and eye pain due to the neovascularization of the retina (vitreous hemorrhage and retinal detachment) and iris (neovascular glaucoma). The literature review revealed that the prevalence of hepatomegaly and abnormal triglyceride levels were significantly higher in female than in male with MDPL syndrome carrying mutations.

Conclusion: These results expand our knowledge regarding the clinical phenotypes of MDPL syndrome with mutations. Diabetic retinopathy is a non-negligible complication of MDPL syndrome. The phenotype varies among female and male patients with the syndrome. Hepatomegaly and abnormal triglyceride levels are more common in female patients with MDPL syndrome.
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http://dx.doi.org/10.1177/11206721211009179DOI Listing
April 2021

Endogenous Endophthalmitis Caused by Klebsiella pneumoniae: A Ten-Year Retrospective Study in Western China.

Ophthalmic Res 2020 15;63(5):507-516. Epub 2020 Jan 15.

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China,

Objectives: The aim of this study was to analyse the clinical features, microbiology results, management and outcomes of patients with endogenous endophthalmitis caused by Klebsiella pneumoniae in western China.

Methods: A retrospective review of medical records of 10 eyes in 10 subjects diagnosed with endogenous K. pneumoniae endophthalmitis from January 2008 to December 2018 was undertaken.

Results: The top 3 predisposing medical conditions included diabetes mellitus (50%), malignancy (20%) and cardiac stent implantation (10%). Extraocular infective foci were mainly found in the liver (40%), lungs (20%) and kidneys (10%). The positive culture rate was 85.71% (6/7) in vitreous samples, 83.33% (5/6) in blood samples and 100% (4/4) in body fluid samples. Only 20% of the patients, who had good initial visual acuity (VA) better than hand movement (HM), achieved a final VA better than 1.0 (log MAR). The mortality rate was 10%.

Conclusions: Though the prognosis of endogenous K. pneumoniae endophthalmitis is often poor, patients with an initial VA better than HM may have a good prognosis under comprehensive treatments, including vitrectomy, systemic sensitive antibiotic injection and drainage of the primary infection loci.
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http://dx.doi.org/10.1159/000505928DOI Listing
January 2020

Ultrasound-assisted aqueous extraction of total flavonoids and hydroxytyrosol from olive leaves optimized by response surface methodology.

Prep Biochem Biotechnol 2019 24;49(9):837-845. Epub 2019 Jun 24.

School of Pharmacy and Bioengineering, Chengdu University , Chengdu , PR China.

Olive leaves were often extracted with methanol or ethanol at different proportions. In this study, ultrasound-assisted aqueous extraction was adopted for olive leaf extraction. The yields of total flavonoids (TF) and hydroxytyrosol (HT) were optimized by central composite experimental design. Two second-order polynomial equations were established to quantify the relationship between the responses and the processing parameters. Under the optimal condition of extracting at 60 °C for 60 min with the solvent-to-material ratio of 40, TF and HT amounted to 57.31 ± 0.35 and 1.80 ± 0.02 mg/g dry leaves (DL), respectively. The scavenging rate of all extracts against α, α-diphenyl-β-picrylhydrazyl (DPPH) and hydroxyl free radicals was screened. The integrated scores, representing both active ingredients and antioxidant capacity of the extracts, were calculated by principle component analysis (PCA). The optimal extract gained the highest score in PCA. In addition, compared to the extracts from 80% methanol to 44% ethanol, the ultrasound-assisted aqueous extract was richer in TF, HT, and polyphenols, while it also presented stronger ferric reducing antioxidant power (FRAP), but poorer strength to quench hydroxyl radicals. The study indicated that the aqueous extract of olive leaves may present broad potential opportunities in health-care sector.
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http://dx.doi.org/10.1080/10826068.2019.1630648DOI Listing
December 2019

PEGylated Multistimuli-Responsive Dendritic Prodrug-Based Nanoscale System for Enhanced Anticancer Activity.

ACS Appl Mater Interfaces 2018 Oct 11;10(42):35770-35783. Epub 2018 Oct 11.

National Engineering Research Center for Biomaterials , Sichuan University , Chengdu 610064 , China.

A PEGylated multistimuli-responsive dendritic copolymer-doxorubicin (DOX) prodrug-based nanoscale system was developed as a delivery model for hydrophobic drugs. In this system, PEGylation did not only prolong circulation of the nanoscale system in the body (average half-life of 14.6 h, four times longer than that of the free drug), but also allowed the system to aggregate into nanoparticles (NPs) because of interactions between hydrophilic (polyethylene glycol) and hydrophobic (dendritic prodrug) moieties for better uptake through endocytosis (around 150 nm of particle size with a neutrally charged surface for the PEGylated dendritic prodrug with 12.1 wt % of DOX). The dendritic structure was built by bridging poly[ N-(2-hydroxypropyl)methacrylamide] segments with enzyme-responsive GFLG (Gly-Phe-Leu-Gly tetrapeptide) linkers. DOX was released by hydrolyzing the hydrazone bond between DOX and the copolymer framework in the acidic endosomes/lysosomes. In vitro studies on DOX released from the NPs induced mitochondrial dysfunction during apoptosis. By imaging the main organs and tumor tissues from mice treated with the NPs, boosted accumulation of this nanoscale medicine was found in tumor tissues, leading to a decrease in toxicity and side effects to normal tissues and enhancement in drug tolerance. In the 4T1 breast cancer model, these NPs exhibited a superior antitumor efficacy confirmed by inhibiting angiogenesis, proliferation of tumor tissues, and inducing procedural apoptosis of tumor cells. The highest tumor growth inhibition value mediated by the NPs was up to 86.5%. Therefore, this PEGylated multistimuli-responsive dendritic copolymer-DOX prodrug-based nanoscale system may be further explored as an alternative to traditional chemotherapy for breast cancer treatment.
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http://dx.doi.org/10.1021/acsami.8b12232DOI Listing
October 2018

Induced Abortion, Birth Control Methods, and Breast Cancer Risk: A Case-Control Study in China.

J Epidemiol 2019 05 11;29(5):173-179. Epub 2018 Aug 11.

Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University.

Background: The association between induced abortion and birth control methods (including oral contraceptives and intrauterine devices) and breast cancer may vary among countries, due to the different usage and frequency of birth control methods and induced abortion among countries. A better understanding of this association may help in determining safer birth control methods for Chinese women.

Methods: A case-control study was conducted with a total of 794 cases and 805 controls. Standardized questionnaires were used to collect information on demographic characteristics, exposure to induced abortion, birth control methods, and other risk factors for breast cancer. Multivariate logistic regression was conducted to explore the association between birth control methods and breast cancer.

Results: Multivariate logistic regression analyses showed that having a history of medical abortions, ≥3 surgical abortions, or both medical and surgical abortions was associated with an increased risk of breast cancer in post-menopausal women (odds ratio [OR] 2.48; 95% confidence interval [CI], 1.14-5.40). Pre-menopausal women who had used intra-uterine devices (IUDs) for more than 20 years tended to have a lower breast cancer risk than other age-matched pre-menopausal women (OR 0.41; 95% CI, 0.25-0.68). Both pre-menopausal and post-menopausal women who had <20 years exposure to IUDs and those who had used two or more birth control methods (with the exception of women who used IUDs for more than 20 years) tended to have much higher breast cancer risk.

Conclusion: The relationship between induced abortion and birth control methods and breast cancer was complex, though being exposed to induced abortion and two or more birth control methods in one's lifetime appeared to be risk factors for breast cancer in Chinese women.
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http://dx.doi.org/10.2188/jea.JE20170318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445797PMC
May 2019

Meta-analysis of the association between ZNF512B polymorphism rs2275294 and risk of amyotrophic lateral sclerosis.

Neurol Sci 2018 Jul 1;39(7):1261-1266. Epub 2018 May 1.

Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan Province, 610041, People's Republic of China.

Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, appears to result from the combination of genetic and environmental factors. Whether the rs2275294 polymorphism in the ZNF512B gene influences ALS risk is controversial. We meta-analysed the association between rs2275294 and ALS risk based on evidence published in the PubMed database. Five case-control studies involving 2559 patients with sporadic ALS and 5740 controls were analysed. Based on random-effects meta-analysis, the polymorphism rs2275294 was associated with increased risk of ALS disease in an allele model (C vs. T: OR 1.222, 95%CI 1.057 to 1.414, p = 0.007). The available evidence suggests that the ZNF512B polymorphism rs2275294 is associated with ALS risk. These results should be validated in large, well-designed studies, especially in non-Asian populations.
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http://dx.doi.org/10.1007/s10072-018-3411-5DOI Listing
July 2018

Dual Receptor Targeting Cell Penetrating Peptide Modified Liposome for Glioma and Breast Cancer Postoperative Recurrence Therapy.

Pharm Res 2018 Apr 26;35(7):130. Epub 2018 Apr 26.

Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Purpose: Cell penetrating peptides (CPPs) were widely used as motifs for drug delivery to tumor. In former study, an RGD reverse sequence dGR was used to develop active-targeting liposome R8dGR-Lip, which showed well penetrating ability and treatment efficiency on glioma model. However, recurrence after tumor resection caused by post-operative residual cancer cells was a huge obstacle in tumor treatment. In consideration of the effective anti-cancer effect of PTX-R8dGR-Lip when treating glioma in former study, we decide to evaluate its pharmacodynamics on tumor resection models, which were more invasive and resistant.

Method: In vitro, the effectiveness of PTX-R8dGR-Lip in reducing tumor initiating cell (TIC) was investigated using mammosphere formation. In vivo, the inhibition efficiency of PTX-R8dGR-Lip on C6 glioma recurrence and 4 T1 breast cancer recurrence model were evaluated, including tumor bioluminescence imaging, survival rate and immumohistochemical staining, etc..

Results: C6 mammosphere formation rate of PTX-R8dGR-Lip group was 48.06 ± 2.72%, and 4 T1 mammosphere formation rate of PTX-R8dGR-Lip group was 39.51 ± 4.02% when PBS group was set as 100%. C6 and 4 T1 bioluminescent tumor resected model were established, then effectiveness of different PTX-loaded preparations were evaluated on these two models. PTX-R8dGR-Lip could obviously inhibit tumor recurrence, prolong survival rate and reduce tumor tissue invasion.

Conclusion: PTX-R8dGR-Lip could reduce post-operative recurrence rate, prolong survival time, and decrease the proliferation of residual cancer cells through regulating the expression of recurrence-related cytokines.
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http://dx.doi.org/10.1007/s11095-018-2399-0DOI Listing
April 2018

Trans-splicing adeno-associated viral vector-mediated gene therapy is limited by the accumulation of spliced mRNA but not by dual vector coinfection efficiency.

Hum Gene Ther 2004 Sep;15(9):896-905

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA.

Therapeutic application of recombinant adeno-associated virus (AAV) has been limited by its small carrying capacity. To overcome this limitation trans-splicing vectors were developed recently. However, the transduction efficiency of trans-splicing vectors is considerably lower than that of a single intact vector in skeletal muscle. To improve trans-splicing vectors for skeletal muscle gene therapy, we examined whether coinfection efficiency is a rate-limiting factor in the mdx mouse, a model for Duchenne muscular dystrophy. Two different AAV viruses were delivered to the mdx muscle. Similar to previous reports in normal muscle, coinfection efficiency reached approximately 90% in the diseased muscle. This result suggests that coinfection is not a hurdle in dystrophic muscle. Another critical step in the trans-splicing method is the transcription and splicing across the inverted terminal repeat (ITR) junction in the reconstituted genome. To test whether this represented a significant obstacle, we systematically evaluated the transcription, pre-mRNA stability and splicing, and translation in a synthetic lacZ construct that mimicked the reconstituted genome. Although inserting an intron in the lacZ gene had no effect on its expression, inclusion of the ITR junction in the intron reduced expression by 50%. In construct containing the ITR junction, the mRNA transcript level was significantly reduced. This mRNA level reduction was associated with decreased pre-mRNA stability. These data suggest that the accumulation of mRNA is a rate-limiting factor in trans-splicing vector-mediated gene therapy.
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http://dx.doi.org/10.1089/hum.2004.15.896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431462PMC
September 2004