Publications by authors named "Xiaodong Sun"

447 Publications

Acceptability of COVID-19 vaccine in the working-age population in Shanghai city: a cross-sectional study.

Hum Vaccin Immunother 2021 Jul 29:1-5. Epub 2021 Jul 29.

Departmen of Immunization Program, Shanghai Municipal Centers for Disease Prevention and Control, Shanghai, China.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is still an enormous threat to global health and the economy. Although China has adopted effective measures to control the outbreak, there is still a risk of local transmission from imported cases. Meanwhile, considering the high mortality rate and rapid spread of the disease, a safe and effective vaccine is urgently needed to control the pandemic. With COVID-19 vaccines becoming available to the population, it has become important to know about their acceptance in the population. This is important to enable high vaccination coverage rates and reflects the demand within the general population. An cross-sectional survey was conducted during October 2020 in Shanghai using a well-designed questionnaire, which aimed to evaluate the acceptability of COVID-19 vaccines and to identify the factors affecting its acceptability among working-age adults in Shanghai, China. We found that the acceptability of COVID-19 vaccines was high in work-age adults in Shanghai, China. The factors affecting the acceptability of vaccination identified in this study can provide guides to increase COVID-19 vaccine acceptability in future.
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http://dx.doi.org/10.1080/21645515.2021.1949951DOI Listing
July 2021

Jiangnan Dietary Pattern Actively Prevents Muscle Mass Loss: Based on a Cohort Study.

J Hum Nutr Diet 2021 Jul 7. Epub 2021 Jul 7.

General Office, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, 200336, China.

Background: The proportion of sarcopenia in the elderly is very high, but muscle mass loss before sarcopenia covers a wider population. This paper is aimed to analyze the effects of different dietary patterns on muscle mass.

Methods: Both in 2015 and 2018, by multilayer random sampling, the same participants were selected, the same questionnaires and machines were used.

Results: A total of 502 participants were selected. The >65 year-old group showed maximum muscle mass loss in males and females, -1.53 kg ± 4.42 and -1.14 kg ± 2.6 on average, respectively. The cumulative variance of four dietary patterns reached 52.28%. Logistical regression revealed significant differences between "Jiangnan Dietary" groups: Q2 VS. Q1 (OR: 0.356, 95% CI [0.202-0.629]); Q3 VS. Q1 (OR: 0.457, 95% CI [0.262-0.797]). Relative influence factors for muscle mass loss were age, (>65 VS. < 45, OR: 2.027, CI [1.117-3.680]), physical activity (OR: 0.550, CI [0.315-0.960]), income (high VS. low, OR: 0.413, CI [0.210 -0.810]), sex (female VS. male, OR: 0.379, CI [0.235-0.519]).

Conclusions: After 3 years follow-up, participants' muscle mass declined significantly. The "Jiangnan Dietary" pattern prevented muscle mass loss and recommended to the wider population. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jhn.12934DOI Listing
July 2021

Anti-osteoporosis effect and purification of peptides with high calcium-binding capacity from walnut protein hydrolysates.

Food Funct 2021 Jun 30. Epub 2021 Jun 30.

Faculty of Agriculture and Food, Kunming University of Science and Technology, No. 727 South Jingming Road, Kunming, Yunnan 650500, China.

The walnut protein hydrolysate (WPH) was prepared via simulated gastrointestinal digestion. The degree of hydrolysis (DH), amino acid composition, and relative molecular weight distribution of WPH were analyzed. The results showed that the DH of WPH was 11.6%, WPH was rich in Glu and Pro, and the relative average molecular weight of 572 Da accounted for 59.78%. The effects of WPH on osteoporosis were evaluated using a model of retinoic acid-induced osteoporosis rat. Treatment with WPH effectively increased the serum calcium and phosphorus contents, alleviated calcium loss, and reduced tartrate-resistant acid phosphate and alkaline phosphatase activities and bone gla protein content. WPH treatment significantly improved the biomechanical properties of the bone and increased the value of bone mineral density. In addition, WPH treatment improved the bone microstructure. WPH was isolated and purified by Sephadex G-25 gel filtration chromatography and semi-preparative reversed-phase high-performance liquid chromatography. A fraction with high calcium-binding activity was obtained and 15 peptides were identified.
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http://dx.doi.org/10.1039/d1fo01094hDOI Listing
June 2021

Modeling Cone/Cone-Rod Dystrophy Pathology by AAV-Mediated Overexpression of Mutant CRX Protein in the Mouse Retina.

Transl Vis Sci Technol 2021 06;10(7):25

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: This study aims to evaluate the pathogenesis of cone/cone-rod dystrophy (CoD/CoRD) caused by a cone-rod homeobox (CRX) mutation, which was identified in a Chinese family, through adeno-associated virus (AAV)-mediated overexpression of mutant CRX protein in the mouse retina.

Methods: Comprehensive ophthalmologic examinations were performed for the pedigree members of a Chinese family with CoD/CoRD. Whole exome sequencing and Sanger sequencing were performed to determine the genetic cause of the disease. Furthermore, AAV vectors were used to construct AAV-CRX-mut-HA, which was transfected into mouse photoreceptor cells to clarify the pathogenesis of the mutant CRX.

Results: Fundus photography and optical coherence tomography images displayed features that were consistent with CoD/CoRD, including macular atrophy and photoreceptor layer thinning. Electroretinogram analysis indicated an obvious decrease in photopic responses or both scotopic and photopic responses in affected individuals. A frameshift variant c.611delC (p.S204fs) in CRX was cosegregated with the disease in this family. AAV-CRX-mut-HA that subretinally injected into the C57BL/6 mice generally transfected the outer nuclear layer, leading to the loss of cone and rod photoreceptor cells, abnormal expression of CRX target genes, and a decrease in electroretinogram responses.

Conclusions: AAV-mediated overexpression of CRX[S204fs] in the mouse retina led to a CoRD-like phenotype and showed the possible pathogenesis of the antimorphic CRX mutation.

Translational Relevance: This study provides a modeling method to evaluate the pathogenesis of CoD/CoRD and other inherited retinal dystrophies caused by distinct gain-of-function mutations.
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http://dx.doi.org/10.1167/tvst.10.7.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237110PMC
June 2021

The Interaction Between Microglia and Macroglia in Glaucoma.

Front Neurosci 2021 28;15:610788. Epub 2021 May 28.

Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.

Glaucoma, a neurodegenerative disease that leads to irreversible vision loss, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic axons. To date, elevated intraocular pressure (IOP) has been recognized as the main phenotypic factor associated with glaucoma. However, some patients with normal IOP also have glaucomatous visual impairment and RGC loss. Unfortunately, the underlying mechanisms behind such cases remain unclear. Recent studies have suggested that retinal glia play significant roles in the initiation and progression of glaucoma. Multiple types of glial cells are activated in glaucoma. Microglia, for example, act as critical mediators that orchestrate the progression of neuroinflammation through pro-inflammatory cytokines. In contrast, macroglia (astrocytes and Müller cells) participate in retinal inflammatory responses as modulators and contribute to neuroprotection through the secretion of neurotrophic factors. Notably, research results have indicated that intricate interactions between microglia and macroglia might provide potential therapeutic targets for the prevention and treatment of glaucoma. In this review, we examine the specific roles of microglia and macroglia in open-angle glaucoma, including glaucoma in animal models, and analyze the interaction between these two cell types. In addition, we discuss potential treatment options based on the relationship between glial cells and neurons.
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http://dx.doi.org/10.3389/fnins.2021.610788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193936PMC
May 2021

The analgesic efficacy of extracorporeal shock wave combined with percutaneous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures in postmenopausal women.

Biomed Eng Online 2021 Jun 10;20(1):58. Epub 2021 Jun 10.

Department of Spinal Surgery, Affiliated Hospital of Weifang Medical University, Weifang, 261031, China.

Background: To explore the analgesic efficacy of extracorporeal shock wave (ESW) combined with percutaneous vertebroplasty (PVP) after reduction in overextension position in the treatment of osteoporotic thoracolumbar compression fractures in postmenopausal women.

Methods: The data of postmenopausal women with osteoporotic thoracolumbar compression fracture admitted in our department from January 2017 to October 2019 were analyzed retrospectively. They were divided into groups of unipedicular percutaneous kyphoplasty (U-PKP n = 21), bipedicular PKP (B-PKP n = 20), and ESW combined with PVP after reduction in overextension position (EP-PVP n = 18). The improvement of pain and vertebral height in three groups was compared.

Results: Postoperative compression rate and Cobb angle of vertebral fractures in the three groups were all lower than those before surgery, and the differences between pre-operation and post-operation were statistically significant (P < 0.05). The visual analog scale (VAS) and Oswestry dysfunction index (ODI) scores of the three groups decreased significantly after the operation (P < 0.05). The ODI scores of the EP-PVP group in the third months after the operation were significantly improved compared with the other two groups, and the difference was statistically significant (P < 0.05).

Conclusions: In our small-sample study, all three treatment schemes can treat osteoporotic compression fracture of thoracolumbar vertebrae in postmenopausal women, relieve pain, and improve quality of life. ESW combined with PVP after reduction in overextension position could achieve a good vertebral reduction rate and improve kyphosis, and may reduce the application of analgesic drugs.
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http://dx.doi.org/10.1186/s12938-021-00894-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194152PMC
June 2021

Novel umami peptides from tilapia lower jaw and molecular docking to the taste receptor T1R1/T1R3.

Food Chem 2021 Nov 30;362:130249. Epub 2021 May 30.

Faculty of Agriculture and Food, Kunming University of Science and Technology, No. 727 South Jingming Road, Kunming, Yunnan 650500, China. Electronic address:

This study aimed to isolate and identify peptides with intense umami taste from tilapia lower jaw. The aqueous extract was separated using ultrafiltration and Sephadex G-15 gel filtration chromatography. The peptide fraction with an intense umami taste was selected by sensory evaluation. The five novel peptides with strong umami taste were VADLMR, STELFK, FVGLQER, DALKKK, and VVLNPVARVE. Electronic tongue analysis and sensory evaluation showed that five peptides had obvious umami taste characteristics, and the recognition thresholds of umami peptides were in the range 0.125-0.250 mg/mL. Molecular docking was used to study the interaction of the peptides and umami taste receptor T1R1/T1R3. The five peptides could perfectly be inserted into the binding pocket of the Venus flytrap domain in the T1R3 subunit. Hydrogen bonding and hydrophobic interaction were the important interaction forces. The five peptides may bind with Asp219, Glu217, and Glu148 in T1R1/T1R3 receptor and produce the umami taste.
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http://dx.doi.org/10.1016/j.foodchem.2021.130249DOI Listing
November 2021

Cost-Effectiveness Analysis of 23-Valent Pneumococcal Polysaccharide Vaccine Program for the Elderly Aged 60 Years or Older in Shanghai, China.

Front Public Health 2021 24;9:647725. Epub 2021 May 24.

School of Public Health, Fudan University, Shanghai, China.

The pneumococcal vaccine has been considered as the most effective measure to prevent pneumococcal diseases. In 2013, Shanghai launched a major public health program to vaccinate people aged 60 years or older with 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV-23) free of charge. By the end of June 2020, a total of 1.56 million old people had been vaccinated free of charge. To evaluate the cost-effectiveness of PPSV-23 vaccination program in Shanghai from the health system perspective. According to the actual number of people aged 60 years or older with PPSV-23 vaccination in Shanghai from 2013 to 2018, a multi-cohort Markov model for life-time was developed to compare health and economic outcomes of vaccinated people vs. if they were not vaccinated for PPSV-23. Cost effectiveness was reported as incremental cost effectiveness ratio (ICER). A 5% discount rate was used for both costs and health outcomes. In addition, one-way sensitivity analysis was used to test the model's robustness. By the end of 2018, a total of 1,091,967 people aged 60 years or older were vaccinated with PPSV-23 in Shanghai, China. Comparing with the unvaccinated circumstances, PPSV-23 vaccination would cost US $19.62 million more and receive an additional 10,321.3 quality-adjusted life-year (QALY). PPSV-23 was associated with the ICER of $190.1 per QALY gained. The Results were sensitive to the variation of vaccine effectiveness against community-acquired pneumonia (CAP), and disease incidence, mortality, and costs of CAP. In all sensitivity analysis, the PPSV-23 was economical. The PPSV-23 vaccination program in Shanghai was cost-effective. With the further development of the project, the administrative costs of the vaccine will be reduced, making it more cost-effective.
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http://dx.doi.org/10.3389/fpubh.2021.647725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181136PMC
June 2021

First Report of Diaporthe longicolla Causing Leaf Spot on Kalanchoe pinnata in China.

Plant Dis 2021 Jun 9. Epub 2021 Jun 9.

National Pesticide Engineering Research Center, Nankai University, Tianjin, Tianjin, Tianjin, China, 300071;

Kalanchoe pinnata (Lam.) Pers. [syn.: Bryophyllum pinnatum (Lam.) Oken] is an important medicinal agent in southern China. The succulent leaves of this plant are used in the treatment of cholera, bruises, uri-nary diseases and whitlow. In Oct. 2019, leaf spots were detected on K. pinnata plants in Chengmai County, Hainan Province, China. Lesions with brown to black margins were irregularly shaped and associated with leaf margins. Spots coalesced to form larger lesions (Fig. S1-A), with black pycnidia present in more mature lesions. Symptomatic K. pinnata were found with 10-20% incidence during the humid winters of Hainan Province. Leaf tissues of 10 symptomatic plants were collected and surface sterilized in 70% ETOH for 30s, 0.1% HgCl2 for 30 s, rinsed 3x with sterile distilled water for 30s, placed on potato dextrose agar (PDA) amended with 30mg/L of kanamycin sulfate, and incubated at 25°C in the dark for 3-5 days. Four fungal isolates were obtained using a single-spore isolation method. The colonies were floccose, dense, and white with forming on older colonies grown on PDA (Fig. S1-B-1&2). Alpha conidia exuded from ostiole, rostrate, long-beaked pycnidia in creamy-to-yellowish drops. Alpha conidia were hyaline, ellipsoidal, separated and averaged 6.3μm (SD ± 1.13) long × 1.9μm (SD ± 0.33) wide (n=50). Beta conidia were not seen. The morphological characteristics matched the previous description of Diaporthe longicolla (syn. Phomopsis longicolla) (Hobbs et al. 1985). Mycelial genomic DNA of the representative isolate LDSG3-2 was extracted as template. The internal transcribed spacer (ITS) , translation elongation factor 1α gene (TEF) and β-tubulin (TUB2) regions were amplified. These loci were amplified using primer pairs ITS4/ITS5 (White, et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999) and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. A BLAST search of GenBank showed ITS (MN960195), TEF (MN974483) and TUB2 (MN974482) sequences of the isolate were 99%, 100%, and 99% homologous with D. longicolla strains DL11 (MF125048, 557/563 bp), D55 (MN584792, 347/347 bp) and DPC-HOH-32 (MK161506, 502/504 bp). Maximum likelihood trees based on concatenated nucleotide sequences of the three genes were constructed using MEGA 7.0, and bootstrap values indicated the isolate was D. longicolla (Fig. S1-D). Pathogenicity testing was performed using isolate LDSG3-2 by depositing 5µl droplets of a conidial suspension (1 × 106 ml-1) into 5 artificially wounded leaves (using a sterile needle) of 10 healthy 3-month-old K. pinnata plants. An equal number of artificially wounded control leaves were inoculated with sterile water to serve as a negative control. The test was conducted three times. Plants were kept at 25°C in 80% relative humidity and observed for symptoms. Two weeks after inoculation, no symptoms were observed on control plants (Fig. S1-C-1) and all inoculated plants showed symptoms (Fig. S1-C-2) similar to those observed in the field. The fungus was re-isolated from the infected tissues and showed the same cultural and morphological characteristics of the strain inoculated and could not be isolated from the controls fulfilling Koch's postulates. To our knowledge, this is the first report of leaf spot on K. pinnata caused by D. longicolla in China. This disease is of concern since Phomopsis diseases are common in K. pinnata fields and can cause significant reduction in yield. References: White, T. J., et al. 1990. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA. DOI: 10.1016/0167-7799(90)90215-J Carbone, I., and Kohn, L. M. 1999. Mycologia. 91:553. DOI: 10.2307/3761358 Glass, N. L., and Donaldson, G. C. 1995. Appl. Environ. Microbiol. 61:1323. DOI: 10.1002/bit.260460112 Hobbs, T. W. et al. 1985. Mycologia. 77: 535. DOI: 10.2307/3793352.
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http://dx.doi.org/10.1094/PDIS-12-20-2681-PDNDOI Listing
June 2021

Speed sensorless control of a bearingless induction motor based on sliding mode observer and phase-locked loop.

ISA Trans 2021 Jun 1. Epub 2021 Jun 1.

School of Electrical and Information Engineering, Jiangsu University, Zhenjiang 212013, China.

To realize the low-cost and high-performance of a bearingless induction motor (BIM), a speed sensorless control strategy combined with the improved sliding mode observer (SMO) and phase locked-loop (PLL) is proposed. Based on analyzing the principle of the traditional SMO, the improved SMO adopts a switching function that has a double boundary layer structure to reduce the high-frequency jitter. Firstly, the observation equation of the rotor flux is established where the stator current, as well as the rotor flux are two state variables, and then the system stability is discussed with the Lyapunov theory. Secondly, to reduce the rotor chatter and enhance the speed tracking performance a flux electrical angle detecting module is constructed based on the PLL structure that extracts the rotor flux electrical angle and speed from the observed flux component. Finally, the BIM speed sensorless vector control system is established and the simulation results and experimental results are respectively presented by the MATLAB/Simulink simulation platform and a laboratory prototype. Both results prove that this strategy can not only enhance the speed self-detection capability and tracking performance, but can guarantee the excellent self-suspension function as well.
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http://dx.doi.org/10.1016/j.isatra.2021.05.041DOI Listing
June 2021

P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.

J Biochem Mol Toxicol 2021 Jun 6:e22822. Epub 2021 Jun 6.

Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.

The neurotoxicity of local anesthetics (LAs) has attracted more and more attention, However, they lack preventive and therapeutic measures. Many studies have shown that apoptosis plays an important role in the process of LA-induced neurotoxicity. As an important signaling molecule to activate apoptosis, p53 has been proved to be involved in the neurotoxicity induced by LAs, but the mechanism is unclear. In this study, we explored the effect of pifithrin-α (PFT-α), a p53 inhibitor, on apoptosis by ropivacaine (Rop) in vivo and in vitro. Cell viability and apoptosis detected by CCK-8 and a JC-1 apoptosis detection kit, the changes of spinal cord structure observed after hematoxylin and eosin staining, apoptosis of the spinal cord measured by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, behavioral assessment of the nerve Injury evaluated by the detection of sciatic nerve conduction velocity (SNCV) andmechanical withdrawal threshold (MWT), the expression of p53 and many apoptosis-related genes included Bax, Bcl-2, and caspase-3 detected by quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. Results showed that PC12 cell viability decreased because of Rop, but the pretreatment of PFT-α could protect it. And PFT-α reduced the injuries in the spinal cord by Rop included vacuoles or edema. The results of immunofluorescence and immunohistochemistry testing showed that PFT-α inhibited the p53 protein upregulated by Rop. Apoptosis rate and many proapoptotic genes include p53, Bax, caspase-3 messenger RNA, and proteins were increased by Rop, but PFT-α could decrease it. In conclusion, PFT-α inhibited cell apoptosis and spinal cord injuries induced by Rop.
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http://dx.doi.org/10.1002/jbt.22822DOI Listing
June 2021

Efficacy of postoperative radiotherapy combined with taxol+carboplatin chemotherapy regimens in the treatment of high-risk early-stage endometrial cancer.

J BUON 2021 Mar-Apr;26(2):561-568

Department of Oncology, Yanan University Affiliated Hospital, Yanan, China.

Purpose: To compare the efficacy and safety of postoperative extrapelvic irradiation intensity-modulated radiotherapy (IMRT)+concurrent chemotherapy and vaginal brachytherapy (VBT)+concurrent chemotherapy in the treatment of patients with high-risk early-stage endometrial cancer, and analyze the influencing factors for the prognosis of patients.

Methods: A total of 126 patients with high-risk stage Ic-IIa endometrial cancer were divided into extrapelvic irradiation IMRT + concurrent taxol+carboplatin (TC) chemotherapy group (IMRT group, n=63) and VBT + concurrent TC chemotherapy group (VBT group, n=63). Then, the efficacy and the incidence rate of adverse reactions were compared between the two groups of patients. Additionally, the possible influencing factors for the prognosis of patients were analyzed.

Results: In the Functional Assessment of Cancer Therapy-General Version 4 (FACT-G-V4) scale for the quality of life of patients, the scores of physiological status, social/family status, emotional status and functional status were dramatically higher in the VBT group than in the IMRT group at 3 months after treatment. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 87.3% and 73.0% in the IMRT group and 82.5% and 66.7% in the VBT group, respectively. Furthermore, advanced age, lower uterine segment involvement and anemia before treatment were independent risk factors for tumor progression in patients with endometrial cancer.

Conclusions: For patients with high-risk early-stage endometrial cancer, postoperative VBT + concurrent TC chemotherapy has similar efficacy to postoperative extrapelvic irradiation IMRT + concurrent TC chemotherapy, but patients receiving the former have fewer adverse reactions and high quality of life. Advanced age, lower uterine segment involvement and anemia before treatment are independent risk factors affecting tumor progression in such patients.
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June 2021

Hydroxypropyl-β-Cyclodextrin-Complexed Resveratrol Enhanced Antitumor Activity in a Cervical Cancer Model: Analysis.

Front Pharmacol 2021 15;12:573909. Epub 2021 Apr 15.

Hubei Clinical Institute of Parkinson's Disease at Xiangyang No .1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, China.

-resveratrol (RES) exhibits a wide range of biological activities. Various methodological approaches have been established to improve the pharmacokinetic properties of RES. Moreover, additional studies are required to support clinical application. In this study, RES/HP-β-CD (RHSD) inclusion complex was prepared and characterized by FTIR, PXRD, DSC and NMR data. The effect and potential mechanism of RHSD against cervical cancer were investigated in a mouse xenograft tumor model by qPCR assay, Western blot assay, and immunohistochemical assay. Results showed that RHSD significantly decreased tumor growth compared with free RES, while the effect of preventing tumor growth was more prominent . Notably, RHSD could inhibit tumor development by suppressing the expression of HPV E6 and E7 oncogenes and upregulating P53 and Rb1 protein in cervical cancer. These findings demonstrated that RHSD was safe and potential for development of a new oral administration drug to treat cervical cancer.
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http://dx.doi.org/10.3389/fphar.2021.573909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082405PMC
April 2021

Alantolactone inhibits cervical cancer progression by downregulating BMI1.

Sci Rep 2021 Apr 29;11(1):9251. Epub 2021 Apr 29.

Hubei Clinical Research Center for Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, 442000, People's Republic of China.

Cervical cancer is the second most common cancer in women. Despite advances in cervical cancer therapy, tumor recurrence and metastasis remain the leading causes of mortality. High expression of BMI1 is significantly associated with poor tumor differentiation, high clinical grade, and poor prognosis of cervical cancer, and is an independent prognostic factor in cervical carcinoma. Alantolactone (AL), a sesquiterpene lactone, exhibits potent anti-inflammatory and anticancer activities. In this paper, we investigated the mechanism of AL in reducing the proliferation, migration, and invasion of HeLa and SiHa cervical cancer cells as well as its promotion of mitochondrial damage and autophagy. BMI1 silencing decreased epithelial-mesenchymal transformation-associated proteins and increased autophagy-associated proteins in HeLa cells. These effects were reversed by overexpression of BMI1 in HeLa cells. Thus, BMI1 expression is positively correlated with invasion and negatively correlated with autophagy in HeLa cells. Importantly, AL decreased the weight, volume, and BMI1 expression in HeLa xenograft tumors. Furthermore, the structure of BMI1 and target interaction of AL were virtually screened using the molecular docking program Autodock Vina; AL decreased the expression of N-cadherin, vimentin, and P62 and increased the expression of LC3B and Beclin-1 in xenograft tumors. Finally, expression of BMI1 increased the phosphorylation of STAT3, which is important for cell proliferation, survival, migration, and invasion. Therefore, we suggest that AL plays a pivotal role in inhibiting BMI1 in the tumorigenesis of cervical cancer and is a potential therapeutic agent for cervical cancer.
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http://dx.doi.org/10.1038/s41598-021-87781-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085045PMC
April 2021

Growth differentiation factor 11: a "rejuvenation factor" involved in regulation of age-related diseases?

Aging (Albany NY) 2021 04 22;13(8):12258-12272. Epub 2021 Apr 22.

Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor β superfamily of cytokines, is a critical rejuvenation factor in aging cells. GDF11 improves neurodegenerative and neurovascular disease outcomes, increases skeletal muscle volume, and enhances muscle strength. Its wide-ranging biological effects may include the reversal of senescence in clinical applications, as well as the ability to reverse age-related pathological changes and regulate organ regeneration after injury. Nevertheless, recent data have led to controversy regarding the functional roles of GDF11, because the underlying mechanisms were not clearly established in previous studies. In this review, we examine the literature regarding GDF11 in age-related diseases and discuss potential mechanisms underlying the effects of GDF11 in regulation of age-related diseases.
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http://dx.doi.org/10.18632/aging.202881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109099PMC
April 2021

Laparoscopic surgery and robotic surgery for single-incision cholecystectomy: an updated systematic review.

Updates Surg 2021 Apr 22. Epub 2021 Apr 22.

Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.

The role of single-incision laparoscopic cholecystectomy (SILC) and single-incision robotic cholecystectomy (SIRC) is still unclear. We update the summarization of the feasibility and safety of SILC and SIRC. A comprehensive search of SILC and SIRC of English literature published on PubMed database between January 2015 and November 2020 was performed. A total of 70 articles were included: 41 covering SILC alone, 21 showing SIRC alone, 7 reporting both, and 1 study not specified. In total, 7828 cases were recorded (SILC/SIRC/not specified, 6234/1544/50); and the gender of 7423 cases was definitively reported: the female rate was 64.0% (SILC/SIRC/not specified, 62.1%/71.5%/74.0%). The weighted mean for body mass index (BMI), operative time, blood loss and post-operative hospital stay was 25.5 kg/m (SILC/SIRC, 25.0/27.0 kg/m), 73.8 min (SILC/SIRC, 68.2/88.8 min), 12.6 mL (SILC/SIRC, 12.1/14.8 mL) and 2.5 days (SILC/SIRC, 2.8/1.9 days), respectively. The pooled prevalence of an additional port, conversion to open surgery, post-operative complications, intraoperative biliary injury, and incisional hernia was 4.1% (SILC/SIRC, 4.7%/1.9%), 0.9% (SILC/SIRC, 0.7%/1.5%), 5.9% (SILC/SIRC, 6.2%/4.1%), 0.1% (SILC/SIRC, 0.2%/0.09%), and 2.1% (SILC/SIRC, 1.4%/4.8%), respectively. Compared with conventional laparoscopic cholecystectomy, SIRC has experienced more postoperative incisional hernias (risk difference = 0.05, 95% confidence interval 0.02-0.07; P < 0.0001). By far, SILC and SIRC have not been considered a standard procedure. With the innovation of medical devices and gradual accumulation of surgical experience, feasibility and safety of performing SILC and SIRC will improve.
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http://dx.doi.org/10.1007/s13304-021-01056-wDOI Listing
April 2021

Peripapillary Vessel Density in Eyes with Rhegmatogenous Retinal Detachment after Pars Plana Vitrectomy.

J Ophthalmol 2021 23;2021:6621820. Epub 2021 Mar 23.

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: To investigate the vascular density of the optic nerve head (ONH) and macula using optical coherence tomography angiography (OCTA) in patients undergoing vitrectomy for rhegmatogenous retinal detachment (RRD) and to evaluate associations with visual outcomes.

Methods: Patients with RRD, successfully treated with a pars plana vitrectomy (PPV) and a minimum three-month follow-up were included in this study. The vessel density (VD) of the ONH and peripapillary regions, foveal avascular zone (FAZ), foveal flow density (FFD), and parafoveal flow density (PFD) were evaluated using OCTA and compared to the fellow eye. Multivariate linear regression analysis was performed to determine correlations with visual outcomes.

Results: Thirty-one patients with macula-off RRD were included in the study. Compared with the fellow eyes, eyes after RRD surgery had a lower peripapillary VD ( < 0.01). No significant difference in superficial and deep FFD, PFD, and FAZ area was found compared to the fellow eyes. Postoperative peripapillary VD and baseline BCVA were significantly associated with BCVA three months after PPV ( < 0.05).

Conclusion: Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower peripapillary vessel density than fellow healthy eyes. Postoperative BCVA was related to postoperative peripapillary VD.
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http://dx.doi.org/10.1155/2021/6621820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009721PMC
March 2021

Small dome-shaped pigment epithelium detachment in polypoidal choroidal vasculopathy: an under-recognized sign of polypoidal lesions on optical coherence tomography?

Eye (Lond) 2021 Apr 8. Epub 2021 Apr 8.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) and swept-source optical coherence tomographic angiography (SS-OCTA) to identify polypoidal lesions in serous or serosanguinous maculopathy.

Materials And Methods: A retrospective review of patients presenting pigment epithelial detachments (PEDs) with the diagnosis of polypoidal choroidal vasculopathy (PCV), neovascular age-related macular degeneration (nAMD), and central serous chorioretinopathy (CSC), all of which underwent SD-OCT, SS-OCTA, and indocyanine green angiography (ICGA). Typical features of polypoidal lesions on SD-OCT included sharply peaked PED, notched PED, and hyperreflective ring underneath PED. SS-OCTA feature was vascularized PEDs on cross-sectional images corresponding to cluster-like structures on en face images. The parameters of PEDs were measured for analysis.

Results: Of 72 eyes, 30 had PCV, 22 had nAMD, and 20 had CSC. A total of 128 localized PEDs were detected on SD-OCT. Typical features on SD-OCT had a high specificity (94.0%) but a limited sensitivity (73.8%). SS-OCTA features provided a higher sensitivity (96.7%). PEDs of the polypoidal lesions unrecognized by SD-OCT were dome-shaped, with smaller ratio of height to base diameter and less area, and almost had heterogeneous internal reflectivity and a connected double-layer sign. Some lesions misidentified by SS-OCTA developed into ICGA-proven polypoidal lesions at follow-up visits.

Conclusion: A small dome-shaped PED with heterogeneous internal reflectivity and a connected double-layer sign on SD-OCT may suggest a polypoidal lesion of PCV. SS-OCTA may be a helpful tool to investigate preclinical PCV and observe the formation of polypoidal lesions.
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http://dx.doi.org/10.1038/s41433-020-01390-0DOI Listing
April 2021

Replacement of polyps with type 1 macular neovascularization in polypoidal choroidal vasculopathy imaged with swept source OCT angiography.

Am J Ophthalmol Case Rep 2021 Jun 11;22:101057. Epub 2021 Mar 11.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Purpose: To investigate the morphological changes of polyps in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors using swept source optical coherence tomography angiography (SS-OCTA).

Observations: Following anti-VEGF therapy, polyps were found to evolve into typical type 1 macular neovascularization (MNV) in five eyes. In all of these five eyes, a polypoidal lesion was detected adjacent to a serous or hemorrhagic retinal pigment epithelial detachment (PED).

Conclusions And Importance: Polypoidal lesions in PCV can evolve into typical type 1 MNV. This morphological evolution suggests that these polyps are clusters of tangled vessels that can proliferate into a more typical neovascular pattern, and this evolution may be facilitated by being adjacent to a PED. Since this morphological appearance could be associated with a better prognosis, SS-OCTA might be helpful in identifying cases of transformed polyps that may be associated with a decreased risk for vision loss.
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http://dx.doi.org/10.1016/j.ajoc.2021.101057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995480PMC
June 2021

How to recognize and respond to viral re-positivity and disease relapse in patients with COVID-19.

J Glob Health 2021 Mar 1;11:03043. Epub 2021 Mar 1.

Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.

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http://dx.doi.org/10.7189/jogh.11.03043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956052PMC
March 2021

MicroRNA-191-5p ameliorates amyloid-β -mediated retinal pigment epithelium cell injury by suppressing the NLRP3 inflammasome pathway.

FASEB J 2021 04;35(4):e21184

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.

Amyloid β (Aβ) is a crucial component of drusen, the hallmark of the early stage of age-related macular degeneration (AMD), and can cause retinal pigment epithelium (RPE) cell damage through activation of the inflammatory response. MicroRNAs play a critical role in inflammation. However, the mechanism underlying the effect of microRNAs on the NLRP3 inflammasome induced by Aβ remains poorly understood. In the present study, we demonstrated that Aβ -mediated RPE damage by inducing a decrease in endogenous miR-191-5p expression. This led to the upregulation of its target gene, C/EBPβ. C/EBPβ acts as a transcription factor for NLRP3, promotes its transcription, and upregulates the downstream inflammatory factors Caspase-1 and IL-1β. Correspondingly, overexpression of miR-191-5p alleviated RPE cell injury by suppressing inflammation. The present study elucidates a novel transcriptional regulatory mechanism of the NLRP3 inflammasome. Our findings suggest an anti-inflammatory effect of miR-191-5p in Aβ -induced RPE impairment, shedding light on novel preventive or therapeutic approaches for AMD-associated RPE impairment.
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http://dx.doi.org/10.1096/fj.202000645RRDOI Listing
April 2021

Bilayer ventilated labyrinthine metasurfaces with high sound absorption and tunable bandwidth.

Sci Rep 2021 Mar 12;11(1):5829. Epub 2021 Mar 12.

Department of Materials Science, Key Laboratory of Micro- and Nano-Photonic Structures (Ministry of Education), and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, China.

The recent advent of acoustic metamaterials offers unprecedented opportunities for sound controlling in various occasions, whereas it remains a challenge to attain broadband high sound absorption and free air flow simultaneously. Here, we demonstrated, both theoretically and experimentally, that this problem can be overcome by using a bilayer ventilated labyrinthine metasurface. By altering the spacing between two constituent single-layer metasurfaces and adopting asymmetric losses in them, near-perfect (98.6%) absorption is achieved at resonant frequency for sound waves incident from the front. The relative bandwidth of absorption peak can be tuned in a wide range (from 12% to 80%) by adjusting the open area ratio of the structure. For sound waves from the back, the bilayer metasurface still serves as a sound barrier with low transmission. Our results present a strategy to realize high sound absorption and free air flow simultaneously, and could find applications in building acoustics and noise remediation.
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http://dx.doi.org/10.1038/s41598-021-84986-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955050PMC
March 2021

SLC7A11 Reduces Laser-Induced Choroidal Neovascularization by Inhibiting RPE Ferroptosis and VEGF Production.

Front Cell Dev Biol 2021 18;9:639851. Epub 2021 Feb 18.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

In age-related macular degeneration (AMD), one of the principal sources of vascular endothelial growth factor (VEGF) is retinal pigment epithelium (RPE) cells under hypoxia or oxidative stress. Solute carrier family 7 member 11 (SLC7A11), a key component of cystine/glutamate transporter, regulates the level of cellular lipid peroxidation, and restrains ferroptosis. In our study, we assessed the role of SLC7A11 in laser-induced choroidal neovascularization (CNV) and explored the underlying mechanism. We established a mouse model of CNV to detect the expression level of SLC7A11 and VEGF during disease progression. We found the expression of the SLC7A11 protein in RPE cells peaked at 3 days after laser treatment, which was correlated with the expression of VEGF. Intraperitoneal injection of SLC7A11 inhibitor expanded the area of CNV. We examined functional proteins related to oxidative stress and Fe and found laser-induced ferroptosis accompanied by increased Fe content and GPX4 expression in the RPE-choroidal complex after laser treatment. We verified the expression of SLC7A11 in the ARPE19 cell line and the effects of its inhibitors on cell viability and lipid peroxidation . Application of SLC7A11 inhibitor and SLC7A11 knockdown increased the level of lipid peroxidation and reduced the cell viability of ARPE19 which can be rescued by ferroptosis inhibitors ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1). Conversely, SLC7A11 overexpression induced resistance to erastin or RSL3-induced ferroptosis. Moreover, we tested the possible regulatory transcription factor NF-E2-related factor 2 (NRF2) of SLC7A11 by Western blot. Knock-down of NRF2 decreased the expression of SLC7A11. Our study suggests that SLC7A11 plays a key role in the laser-induced CNV model by protecting RPE cells from ferroptosis. SLC7A11 provides a new therapeutic target for neovascular AMD patients.
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http://dx.doi.org/10.3389/fcell.2021.639851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930391PMC
February 2021

Effect of roasted peanut allergen Ara h 3 protein on the sensitization of Caco-2 cells.

J Sci Food Agric 2021 Mar 1. Epub 2021 Mar 1.

School of Life Sciences, Shanghai University, Shanghai, China.

Background: Roasted peanut is widely loved as a kind of food with rich taste. However, peanut allergy is one of the major threats to human health, which affects about 5% of children and 1.4-2% of adults in the world.

Results: To evaluate the sensitization mechanism of peanut allergen Ara h 3, Caco-2 cells as the model, which has the similar structure and function to differentiated small intestinal epithelial cells. Compared with Ara h 3-raw (purified from raw peanut) group, more significant results such as the inhibited Caco-2 cell viability and proliferation, the increased secretion of reactive oxygen species (ROS) and the decreased transepithelial electrical resistance were obtained in Ara h 3-roasted (purified from roasted peanut) group. Accordingly, oxidative stress and NF-κB signaling pathway were more imbalanced, which lead to the increased of thymic stromal lymphopoietin (TSLP), interleukin 6 (IL-6), IL-8 and monocyte chemotactic protein 1 (MCP-1). Then, the gene expression of tight junction proteins ZO-1, occludin and JAM-1 were reduced, which proved that the integrity of the Caco-2 monolayer barrier is severely damaged.

Conclusion: These finding identify the mechanisms of the allergenicity of roasted peanut allergy proteins are probably associated with intestinal uptake and cytokine dependent allergies. The aggravated allergic reaction might be caused by the increment of TSLP, IL-6, IL-8 and MCP-1 due to the activated NF-κB signaling pathway, and the enhanced transport of Ara h 3-roasted protein by Caco-2 monolayer. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11180DOI Listing
March 2021

Prostaglandin E promotes pathological retinal neovascularisation via EPR-EGFR-Gab1-AKT signaling pathway.

Exp Eye Res 2021 Apr 17;205:108507. Epub 2021 Feb 17.

Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China; Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China. Electronic address:

Proliferative retinopathies, such as proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP) are major causes of visual impairment and blindness in industrialized countries. Prostaglandin E (PGE) is implicated in cellular proliferation and migration via E-prostanoid receptor (EPR). The aim of this study was to investigate the role of PGE/EPR signaling in the promotion of retinal neovascularisation. In a streptozotocin (STZ)-induced diabetic model and an oxygen-induced retinopathy (OIR) model, rats received an intravitreal injection of PGE, cay10598 (an EPR agonist) or AH23848 (an EPR antagonist). Optical coherence tomography, retinal histology and biochemical markers were assessed. Treatment with PGE or cay10598 accelerated pathological retinal angiogenesis in STZ and OIR-induced rat retina, which was ameliorated in rats pretreated with AH23848. Serum VEGF-A was upregulated in the PGE-treated diabetic rats vs non-treated diabetic rats and significantly downregulated in AH23848-treated diabetic rats. PGE or cay10598 treatment also significantly accelerated endothelial tip-cell formation in new-born rat retina. In addition, AH23848 treatment attenuated PGE-or cay10598-induced proliferation and migration by repressing the EGF receptor (EGFR)/Growth factor receptor bound protein 2-associated binder protein 1 (Gab1)/Akt/NF-κB/VEGF-A signaling network in human retinal microvascular endothelial cells (hRMECs). PGE/EPR signaling network is thus a potential therapeutic target for pathological intraocular angiogenesis.
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http://dx.doi.org/10.1016/j.exer.2021.108507DOI Listing
April 2021

Antibody seroprevalence in the epicenter Wuhan, Hubei, and six selected provinces after containment of the first epidemic wave of COVID-19 in China.

Lancet Reg Health West Pac 2021 Mar 5;8:100094. Epub 2021 Feb 5.

National Institute for Viral Disease Control and Prevention (China CDC), Beijing, China.

Background: China implemented containment measures to stop SARS-CoV-2 transmission in response to the COVID-19 epidemic. After the first epidemic wave, we conducted population-based serological surveys to determine extent of infection, risk factors for infection, and neutralization antibody levels to assess the real infections in the random sampled population.

Methods: We used a multistage, stratified cluster random sampling strategy to conduct serological surveys in three areas - Wuhan, Hubei Province outside Wuhan, and six provinces selected on COVID-19 incidence and containment strategy. Participants were consenting individuals >1 year old who resided in the survey area >14 days during the epidemic. Provinces screened sera for SARS-CoV-2-specific IgM, IgG, and total antibody by two lateral flow immunoassays and one magnetic chemiluminescence enzyme immunoassay; positive samples were verified by micro-neutralization assay.

Findings: We enrolled 34,857 participants (overall response rate, 92%); 427 were positive by micro-neutralization assay. Wuhan had the highest weighted seroprevalence (4•43%, 95% confidence interval [95%CI]=3•48%-5•62%), followed by Hubei-ex-Wuhan (0•44%, 95%CI=0•26%-0•76%), and the other provinces (<0•1%). Living in Wuhan (adjusted odds ratio aOR=13•70, 95%CI= 7•91-23•75), contact with COVID-19 patients (aOR=7•35, 95%CI=5•05-10•69), and age over 40 (aOR=1•36, 95%CI=1•07-1•72) were significantly associated with SARS-CoV-2 infection. Among seropositives, 101 (24%) reported symptoms and had higher geometric mean neutralizing antibody titers than among the 326 (76%) without symptoms (30±2•4 vs 15±2•1, <0•001).

Interpretation: The low overall extent of infection and steep gradient of seropositivity from Wuhan to the outer provinces provide evidence supporting the success of containment of the first wave of COVID-19 in China. SARS-CoV-2 infection was largely asymptomatic, emphasizing the importance of active case finding and physical distancing. Virtually the entire population of China remains susceptible to SARS-CoV-2; vaccination will be needed for long-term protection.

Funding: This study was supported by the Ministry of Science and Technology (2020YFC0846900) and the National Natural Science Foundation of China (82041026, 82041027, 82041028, 82041029, 82041030, 82041032, 82041033).
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http://dx.doi.org/10.1016/j.lanwpc.2021.100094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864613PMC
March 2021

Retinitis pigmentosa sine pigmento masqueraded as myopia: A case report (CARE).

Authors:
Yi Lu Xiaodong Sun

Medicine (Baltimore) 2021 Jan;100(3):e24006

Department of Ophthalmology, Shanghai General Hospital, Shanghai JiaoTong University.

Introduction: Retinitis pigmentosa is a major cause of visual disability and blindness. Photopsia is usually presented in patients with retinal traction caused by posterior vitreous detachment in clinic, which would occur more commonly in those suffer from moderate or high myopia. We describe a patient with leopard-like retinopathy initially complaining of photopsia caused not by myopia but by retinitis pigmentosa.

Patient Concerns: A 39-year-old woman with a history of moderate myopia presented to us complaining of photopsia for several days.

Diagnosis: Fundus examination revealed leopard-like retinopathy with normal optic disc and macula appearance in both eyes. The atrophy of retinal pigment epithelium was found in peripheral retina while no bone spicule was present. Retinal multimodal imaging helped in the correct diagnosis of retinitis pigmentosa (sine pigmento), later confirmed by genetic testing.

Interventions: At current no specific treatment was applied, but the patient was required for follow-up observation every six months.

Outcomes: Follow-up observation.

Conclusion: This case highlights the potential for retinitis pigmentosa sine pigmento to present with photopsia under cover of myopia and the importance of performing multimodal imaging including fundus autofluorescence for fundus disorders. Careful history review and multimodal imaging with genetic testing would help for the correct diagnosis of retinitis pigmentosa sine pigmento.
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http://dx.doi.org/10.1097/MD.0000000000024006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837948PMC
January 2021

Immunogenicity and safety of the inactivated poliomyelitis vaccine made from Sabin strains in a phase IV clinical trial for the vaccination of a large population.

Vaccine 2021 03 22;39(9):1463-1471. Epub 2021 Jan 22.

Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infections Diseases, Kunming, Yunnan, China. Electronic address:

As a recently launched novel vaccine used as one of the vaccines for the final eradication of polios worldwide, complete data on the consistency and immunogenicity characteristics of the inactivated poliomyelitis vaccine made from the Sabin strain (sIPV) and its safety in large-scale populations are required to support the future use of this vaccine worldwide. A phase IV clinical trial was conducted to perform an immunogenicity evaluation of lot-to-lot consistency of three commercial batches of sIPV in 1200 infants and to investigate the vaccine's safety on a large-scale in 20,019 infants for active monitoring and 29,683 infants for passive monitoring through the Adverse Event Following Immunization (AEFI) reporting system in China. In the immunogenicity evaluation, the average seroconversion rates for type I, type II and type III of the three groups were 99.83%, 98.93% and 99.44%, respectively. No differences in the seroconversion rate and the GMT ratios were noted in the pair-to-pair comparisons. In the large-scale safety evaluation, most adverse reactions occurred 0-30 days after the first doses, and the common local and systemic reactions were similar to those in the phase III clinical trial, with low incidence in both activated and passive monitoring. In conclusion, sIPV exhibits good lot-to-lot consistency and safety in large-scale populations; thus, it is qualified to serve as one of the vaccines for use in eradicating all wild and vaccine-derived polioviruses worldwide in the near future. Clinic Trial Registration. NCT04224519 and NCT04220515.
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http://dx.doi.org/10.1016/j.vaccine.2021.01.027DOI Listing
March 2021

Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa-targeting guide RNA prevents wet age-related macular degeneration in mice.

Nat Biomed Eng 2021 02 4;5(2):144-156. Epub 2021 Jan 4.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

Therapeutic genome editing requires effective and targeted delivery methods. The delivery of Cas9 mRNA using adeno-associated viruses has led to potent in vivo therapeutic efficacy, but can cause sustained Cas9 expression, anti-Cas9 immune responses and off-target edits. Lentiviral vectors have been engineered to deliver nucleases that are expressed transiently, but in vivo evidence of their biomedical efficacy is lacking. Here, we show that the lentiviral codelivery of Streptococcus pyogenes Cas9 mRNA and expression cassettes that encode a guide RNA that targets vascular endothelial growth factor A (Vegfa) is efficacious in a mouse model of wet age-related macular degeneration induced by Vegfa. A single subretinal injection of engineered lentiviruses knocked out 44% of Vegfa in retinal pigment epithelium and reduced the area of choroidal neovascularization by 63% without inducing off-target edits or anti-Cas9 immune responses. Engineered lentiviruses for the transient expression of nucleases may form the basis of new treatments for retinal neovascular diseases.
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http://dx.doi.org/10.1038/s41551-020-00656-yDOI Listing
February 2021

Human retinal pigment epithelial cells are protected against hypoxia by BNIP3.

Ann Transl Med 2020 Nov;8(22):1502

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

Background: Hypoxia has been implicated in the process of retinal pigment epithelium (RPE) dysfunction. However, recent studies suggest that hypoxia contributes to survival rather than cell death through induction of Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3)-dependent autophagy. In contrast, persistent oxidative stress was found to result in autophagy dysregulation in RPE cells. These seemingly contradictory findings led us to investigate the potential role of BNIP3, a crucial mediator of hypoxia-induced autophagy, in the context of hypoxic RPE cells.

Methods: Human RPE D407 cells were treated with low-oxygen conditions, and cell growth, apoptosis, and autophagy was assessed by Cell Counting Kit-8 assay, flow cytometry analysis and immunofluorescence staining, respectively.

Results: Hypoxic conditions simultaneously triggered a large amount of apoptosis and inhibited autophagy. Moreover, hypoxia led to severe impairments, including the stimulation of reactive oxygen species, and reduction of mitochondrial membrane potential, and adenosine triphosphate production. The stimulation of autophagy by rapamycin inhibited hypoxia-induced severe impairments to a great extent. Interestingly, similar results were observed for BNIP3 overexpression, which can be largely blocked by 3-MA, a well-defined inhibitor of autophagy. Moreover, BNIP3 knockdown further aggravated hypoxia-induced impairments in D407 cells, which can be reversed by rapamycin.

Conclusions: Collectively, these results indicated that BNIP3 can protect human retinal pigmented epithelial cells under hypoxic conditions by inducing autophagy.
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http://dx.doi.org/10.21037/atm-20-7145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729317PMC
November 2020
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