Publications by authors named "Zhiyong Chen"

225 Publications

Retraction notice to "Synthesis and bioevaluation of aryl-guanidino polyamine conjugates targeting the polyamine transporter" [Bioorg. Med. Chem. Lett. 20 (2010) 6421-6425].

Bioorg Med Chem Lett 2021 Jul 10:128251. Epub 2021 Jul 10.

Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China.

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http://dx.doi.org/10.1016/j.bmcl.2021.128251DOI Listing
July 2021

Comparing compressed sensing breath-hold 3D MR cholangiopancreatography with two parallel imaging MRCP strategies in main pancreatic duct and common bile duct.

Eur J Radiol 2021 Jun 24;142:109833. Epub 2021 Jun 24.

Diagnostic Imaging, Siemens Healthcare, Shanghai, China.

Purpose: To evaluate the image quality and image consistency between 3D Breath-hold (BH)-MRCP with parallel imaging (3D-BH-PI-MRCP) and 3D-BH compressed sensing (CS)-MRCP (3D-BH-CS-MRCP) in patients with suspected pancreaticobiliary diseases, compared with 3D navigator-triggered (NT)-MRCP.

Materials And Methods: The A total number of 109 patients who underwent 3D-NT-MRCP, 3D-BH-PI-MRCP and 3D-BH-CS-MRCP were prospectively enrolled in this study. The Friedman test was performed to compare quantitative values, image acquisition time, the presence of artifacts, overall image quality, and duct visualization among the three protocols. Additionally, we compared 3D-BH-PI-MRCP and 3D-BH-CS-MRCP with 3D-NT-MRCP in morphological consistency of main pancreatic duct and common bile duct (CBD) based on overall image quality score of = 4.

Results: Three MRCP methods were successfully performed in all the patients. The contrast ratio, SNR and CNR of the CBD were significantly higher for 3D-BH-CS-MRCP than those for 3D-NT-MRCP and 3D-BH-PI-MRCP images. Overall image quality did differ significantly across the three sequences. Visualization of the CBD, RHD, LHD, anterior branch, posterior branch and cystic duct was similar with the 3D-BH-CS-MRCP and 3D-BH-PI-MRCP sequences. In contrast, segment 2 or 3 branch and main pancreatic duct visualization were significantly better with 3D-BH-PI-MRCP than with 3D-BH-CS-MRCP and 3D-NT-MRCP (p < 0.001).

Conclusions: Both the two breath-hold approaches were considering the time-saving advantages without deterioration of image quality. Compared with 3D-BH-CS-MRCP, 3D-BH-PI-MRCP yielded significantly better visualization of the segment 2 and 3 branch of the intrahepatic duct and performed better consistency in main pancreatic duct and common bile duct morphology.
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http://dx.doi.org/10.1016/j.ejrad.2021.109833DOI Listing
June 2021

Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo.

J Inflamm Res 2021 25;14:2207-2223. Epub 2021 May 25.

Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People's Republic of China.

Background: Activation of vascular adventitial fibroblasts (VAFs) upon vascular injury contributes greatly to the medial vascular smooth muscle cells (VSMCs) proliferation, migration and the subsequent neointima formation. A number of factors including fibroblast growth factors (FGFs) have been shown to control VSMC growth, proliferation and phenotypic switching, suggesting that they may function as paracrine signals for VAFs to modulate VSMCs functions. However, little is known about the signaling molecule(s) and its mechanism of action. This study is set to identify which and how FGF family members are involved in VAFs mediated vascular remodeling.

Methods: We used qPCR, Western blot and Immunohistochemistry to observe the spatiotemporal expression of FGF10 and FGFR2 in injured vascular tissue. The proliferation and migration assays of VSMCs were performed in a co-culture system. The activation of signaling pathway was detected by Western blot, immunohistochemistry and immunofluorescence. Hematoxylin-eosin and immunofluorescence were used to assess the effects of exogenous FGF10 and siFGF10 on the neointima formation.

Results: The expression of FGF10 and FGFR2 were increased from day 3 through day 14 post injury. FGF10 was significantly upregulated in adventitia, and FGFR2 was detected in both media and neointima after injury. In vitro, FGF10 was most prominently expressed in VAFs and FGFR2 was significantly expressed in VSMCs. Both were regulated by PDGF. Co-culture of VAFs and VSMCs in vitro showed that VAF-derived FGF10 promoted the proliferation and migration of VSMCs. PDGF could synergistically enhance the process. VAF-derived FGF10 can significantly activate the FGFR2 in VSMCs and furthermore significantly activate the downstream MAPK/PI3K-AKT signaling pathways. Delivery of exogenous FGF10 potentiated the neointima formation, while siFGF10 attenuated the neointima formation.

Conclusion: VAFs-derived FGF10 promoted the proliferation and migration of VSMCs and neointima formation, and FGF10-FGFR2 signaling triggered the activation of MAPK/PI3K-AKT pathways in VSMCs and PDGF synergistically amplified FGF10 signaling.
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http://dx.doi.org/10.2147/JIR.S305204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164702PMC
May 2021

Role of Two Plant Growth-Promoting Bacteria in Remediating Cadmium-Contaminated Soil Combined with (Lab.).

Plants (Basel) 2021 May 2;10(5). Epub 2021 May 2.

College of Bioscience and Biotechnology, College of Resource and Environment, Hunan Agricultural University, Changsha 410128, China.

spp. are energy plants and excellent candidates for phytoremediation approaches of metal(loid)s-contaminated soils, especially when combined with plant growth-promoting bacteria. Forty-one bacterial strains were isolated from the rhizosphere soils and roots tissue of five dominant plants ( Levl., Vaniot Houtt, L., Tenore, and Lab.) colonizing a cadmium (Cd)-contaminated mining area (Huayuan, Hunan, China). We subsequently tested their plant growth-promoting (PGP) traits (e.g., production of indole-3-acetic acid, siderophore, and 1-aminocyclopropane-1-carboxylate deaminase) and Cd tolerance. Among bacteria, two strains, TS8 and MR2, presented higher Cd tolerance and showed the best results regarding in vitro growth-promoting traits. In the subsequent pot experiments using soil spiked with 10 mg Cd·kg, we investigated the effects of TS8 and MR2 strains on soil Cd phytoremediation when combined with (Lab.). After sixty days of planting (Lab.), we found that TS8 increased plant height by 39.9%, dry weight of leaves by 99.1%, and the total Cd in the rhizosphere soil was reduced by 49.2%. Although MR2 had no significant effects on the efficiency of phytoremediation, it significantly enhanced the Cd translocation from the root to the aboveground tissues (translocation factor > 1). The combination of TS8 and (Lab.) may be an effective method to remediate Cd-contaminated soils, while the inoculation of MR2 may be used to enhance the phytoextraction potential of .
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http://dx.doi.org/10.3390/plants10050912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147505PMC
May 2021

An alternatingly amphiphilic, resistance-resistant antimicrobial oligoguanidine with dual mechanisms of action.

Biomaterials 2021 May 17;275:120858. Epub 2021 May 17.

Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chem-/Bio-Sensing and Chemometrics, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, And School of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan, 410082, China. Electronic address:

The increasing number of infections caused by multi-drug resistance (MDR) bacteria is an omen of a new global challenge. As one of the countermeasures under development, antimicrobial peptides (AMPs) and AMP mimics have emerged as a new family of antimicrobial agents with high potential, due to their low resistance generation rate and effectiveness against MDR bacterial strains resulted from their membrane-disrupting mechanism of action. However, most reported AMPs and AMP mimics have facially amphiphilic structures, which may lead to undesired self-aggregation and non-specific binding, as well as increased cytotoxicity toward mammalian cells, all of which put significant limits on their applications. Here, we report an oligomer with the size of short AMPs, with both hydrophobic carbon chain and cationic groups placed on its backbone, giving an alternatingly amphiphilic structure that brings better selectivity between mammalian and bacterial cell membranes. In addition, the oligomer shows affinity toward DNA, thus it can utilize bacterial DNA located in the vulnerable nucleoid as the second drug target. Benefiting from these designs, the oligomer shows higher therapeutic index and synergistic effect with other antibiotics, while its low resistance generation rate and effectiveness on multi-drug resistant bacterial strains can be maintained. We demonstrate that this alternatingly amphiphilic, DNA-binding oligomer is not only resistance-resistant, but is also able to selectively eliminate bacteria at the presence of mammalian cells. Importantly, the oligomer exhibits good in vivo activity: it cleans all bacteria on Caenorhabditis elegans without causing apparent toxicity, and significantly improves the survival rate of mice with severely infected wounds in a mice excision wound model study.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120858DOI Listing
May 2021

Hereditary Transthyretin Amyloidosis- Clinical and Genetic Characteristics of a Multiracial South-East Asian Cohort in Singapore.

J Neuromuscul Dis 2021 May 15. Epub 2021 May 15.

Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore.

Background And Aims: Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort.

Methods: Patients with genetically proven ATTRv amyloidosis were identified over a 13-year period (2007-2020) at the National Neuroscience Institute, Singapore. Clinical, laboratory, genotypic and electrophysiological features were retrospectively reviewed.

Results: 29 patients comprising Chinese, Malay, Burmese, Vietnamese and Indonesians with ATTRv amyloidosis were identified. Somatic neuropathy was the most common initial presentation, followed by carpal tunnel syndrome, autonomic dysfunction and cardiac dysfunction. ATTR-A97S (p.Ala117Ser) was the most common variant found in 14 patients, constituting 66.7%of ethnic Chinese patients and 48.3%of the entire cohort. Five patients had early-onset disease (age <  50 years) with the following variants: ATTR-V30M (p.Val50Met), ATTR-G47A (p.Gly67Ala), ATTR-S50I (p.Ser70Ile) and ATTR-A97S (p.Ala117Ser); one patient with ATTR-A97S (p.Ala117Ser) had isolated unilateral carpal tunnel syndrome with amyloid deposits identified on histological examination of the transverse carpal ligament. All early-onset patients had a positive parental history; two patients, with ATTR-S50I (p.Ser70Ile) and ATTR-Ala97Ser (p.Ala117Ser) respectively, demonstrated anticipation with mother-to-daughter inheritance. Amongst the 24 patients with late-onset disease (age≥50 years), two patients had novel variants, ATTR-G66D (p.Glu86Asp) and ATTR-A81V (p.Ala101Val) that were confirmed to be pathogenic based on the histological identification of transthyretin amyloid. Other identified variants included ATTR-V30M (p.Val50Met), ATTR-R34T (p.Arg54Thr), ATTR-S50I (p.Ser70Ile), ATTR-H88R (p.His108Arg) and ATTR-A97S (p.Ala117Ser).

Conclusion: Our study further expands the genotypic and phenotypic knowledge regarding ATTRv amyloidosis.
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http://dx.doi.org/10.3233/JND-210656DOI Listing
May 2021

The Protective Effects of Sulforaphane on High-Fat Diet-Induced Obesity in Mice Through Browning of White Fat.

Front Pharmacol 2021 29;12:665894. Epub 2021 Apr 29.

Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Sulforaphane (SFN), an isothiocyanate naturally occurring in cruciferous vegetables, is a potent indirect antioxidant and a promising agent for the control of metabolic disorder disease. The glucose intolerance and adipogenesis induced by diet in rats was inhibited by SFN. Strategies aimed at induction of brown adipose tissue (BAT) could be a potentially useful way to against obesity. However, protective effect of SFN against obesity by browning white adipocyte has not been reported. Our present study is aimed at evaluation the efficacy of the SFN against the high-fat induced-obesity mice and investigating the potential mechanism. High-Fat Diet-induced obese female C57BL/6 mice were intraperitoneally injected with SFN (10 mg/kg) daily. Body weight was recorded every 3 days. 30 days later, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed. At the end of experiment, fat mass were measured and the adipogenesis as well as browning associated genes expression in white adipose tissue (WAT) were determined by RT-qPCR and western blot. Histological examination of the adipose tissue samples were carried out with hematoxylin-eosin (HE) staining and immunofluorescence staining method. , pre-adipocytes C3H10T1/2 were treated with SFN to investigate the direct effects on adipogenesis. SFN suppressed HFD-induced body weight gain and reduced the size of fat cells in mice. SFN suppressed the expression of key genes in adipogenesis, inhibited lipid accumulation in C3H10T1/2 cells, increased the expression of brown adipocyte-specific markers and mitochondrial biogenesis and , and decreased cellular and mitochondrial oxidative stress. These results suggested that SFN, as a nutritional factor, has great potential role in the battle against obesity by inducing the browning of white fat. SFN could significantly decrease the fat mass, and improve glucose metabolism and increase insulin sensitivity of HFD-induced obese mice by promoting the browning of white fat and enhancing the mitochondrial biogenesis in WAT. Our study proves that SFN could serve as a potential medicine in anti-obesity and related diseases.
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http://dx.doi.org/10.3389/fphar.2021.665894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116735PMC
April 2021

Suctioning semirigid ureteroscopic lithotomy versus minimally invasive percutaneous nephrolithotomy for large upper ureteral stones: a retrospective study.

Transl Androl Urol 2021 Mar;10(3):1056-1063

Department of Urology, Xiangya Hospital, Central South University, Changsha, China.

Background: To compare the safety and validity of a suctioning semirigid ureteroscopic lithotomy (Sotn-URSL) and minimally percutaneous nephrolithotomy (mPCNL) in treating upper ureteral stone larger than 15 mm.

Methods: Between February 2018 and December 2019, 97 patients who had upper ureteral stone >15 mm were consecutively included in this study. Forty-six patients underwent Sotn-URSL and 51 underwent mPCNL by the same surgeon. The following parameters were retrospectively assessed: patient and stone characteristics, surgical details, perioperative outcomes, and stone-free rates (SFRs).

Results: No significant difference was observed in two groups for patient and stone characteristics, except that mPCNL group had a higher incidence of severe hydronephrosis (19.6% 41.2%, P=0.021). Sotn-URSL group was similar to mPCNL group in terms of the mean duration of surgery (50.5±5.9 52.9±8.0 min, P=0.106) and the SFR after 1 month (91.3% 98%, P=0.187). The hospital stay after surgery of Sotn-URSL group was significant shorter than mPCNL group (1.4±0.6 2.3±0.7 days, P<0.001), and postoperative complications in Sotn-URSL group was less, especially postoperative pain (P=0.044).

Conclusions: Both mPCNL and Sotn-URSL are suitable for upper ureteral stones with a diameter of >15 mm. Nevertheless, further well-designed studies with long-term follow-up are needed to confirmed the results.
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http://dx.doi.org/10.21037/tau-20-1218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039583PMC
March 2021

Clinical Images: Kimura disease of the earlobe.

ACR Open Rheumatol 2021 May 7;3(5):355. Epub 2021 Apr 7.

Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

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http://dx.doi.org/10.1002/acr2.11257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126751PMC
May 2021

Late embryogenesis abundant (LEA) gene family in : identification, expression analysis, and response to drought stress.

Plant Signal Behav 2021 May 5;16(5):1891769. Epub 2021 Apr 5.

College of Life Science, Northwest A&F University, Yangling Shaanxi, China.

Late embryogenesis abundant (LEA) proteins play important roles in plant defense response to drought stress. However, genome-wide identification of the gene family was not revealed in . In this study, 61 genes were identified from and divided into 7 subfamilies according to their conserved domains and phylogenetic relationships. genes contained the LEA conserved motifs and few introns. genes of the same subfamilies had similar gene structures and predicted subcellular locations. Our results indicated that the promoters of genes contained various -acting elements associated with abiotic stress response. In addition, RNA-seq and real-time PCR results suggested that genes are specifically expressed in different tissue, and most genes can be induced by drought stress. These results provide a valuable foundation for future functional investigations of genes and drought stress-resistant breeding of .
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http://dx.doi.org/10.1080/15592324.2021.1891769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078505PMC
May 2021

Incidence and risk factors of venous thromboembolism after percutaneous nephrolithotomy: a single-center experience.

World J Urol 2021 Mar 16. Epub 2021 Mar 16.

Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, China.

Purpose: To determine the incidence and risk factors of the venous thromboembolism (VTE) in patients undergoing percutaneous nephrolithotomy (PCNL).

Methods: We retrospectively reviewed the records of 896 consecutive cases receiving PCNL between July 2018 and August 2020 in our institution. Univariate analysis was performed to identify the risk factors of VTE, and multivariate logistic regression analysis was further performed to determine the independent risk factors. Furthermore, the corresponding nomogram was conducted to establish a predicted model for VTE.

Results: The overall incidence of VTE was 2.8%. The multivariate logistic regression analysis showed that discontinued anticoagulant or antiplatelet therapies (OR 4.505, 95% CI 1.410-14.401), increased postoperative 12-h D-dimer (OR 11.162, 95% CI 2.370-52.574), hydronephrosis (OR 3.303, 95% CI 1.303-8.375), higher Caprini risk assessment model (RAM) score (OR 3.233, 95% CI 1.207-8.659) and postoperative sepsis or septic shock (OR 3.784, 95% CI 1.163-12.306) were independent risk factors of VTE following PCNL. Moreover, the area under the curve of postoperative 12-h D-dimer, hydronephrosis and Caprini RAM score was 0.826, 0.621 and 0.660, respectively. Based on the identified independent risk factors, the well-calibrated nomogram showed a moderate discriminative ability with concordance index 0.731.

Conclusions: 2.8% of patients developed VTE following PCNL. Regarding those patients who have independent risk factors in this study, due attention should be paid to the effective thromboprophylaxis and the early detection of VTE.
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http://dx.doi.org/10.1007/s00345-021-03658-wDOI Listing
March 2021

Chemical compositions, pharmacological activities, quality control studies of Erycibes plants, and the development of their substitutes.

Phytother Res 2021 Mar 16. Epub 2021 Mar 16.

Shaanxi Academy of Traditional Chinese Medicine, Institute of Traditional Chinese Medicine, Xi'an, China.

Erycibes are members of the Convolvulaceae family, including more than 10 species worldwide that are distributed in tropical Asia. Some Erycibes species have long been used as traditional remedies for rheumatoid arthritis, fever, hepatitis, and liver injury in China and Thailand. A total of 152 compounds from Erycibes plants have been isolated and identified, categorized as flavonoids, coumarins, quinic acid derivatives, lignans, and alkaloids. Coumarins are the characteristic and active constituents of this species, including scopoletin and scopolin. Modern pharmacological studies have shown that the extracts and bioactive components of Erycibes plants exhibit several biological activities, including antiinflammatory, analgesic, hepatoprotective, anti-gout, antitumor, antioxidation, and other therapeutic effects. However, in recent years, due to destructive exploitation and utilization, some Erycibes plants' natural resources have become rare or endangered. Developing substitutes is a strategy to alleviate the pressure on those endangered medicinal plant resources. To provide a scientific basis for the development and protection of those threatened Erycibes species, this review summarized the current status of the chemical compositions, pharmacological activities, quality control studies, and the development of substitutes for Erycibes plants. In particular, the rationale for use of Porana sinensis currently on the market is discussed.
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http://dx.doi.org/10.1002/ptr.7070DOI Listing
March 2021

Antibiotic administration for negative midstream urine culture patients before percutaneous nephrolithotomy.

Urolithiasis 2021 Mar 12. Epub 2021 Mar 12.

Department of Urology, Xiangya Hospital of Central South University, 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China.

To investigate how to administrate antibiotics for negative midstream urine culture (UC-) patients prior to percutaneous nephrolithotomy (PCNL), we retrospectively analyzed UC-patients receiving 0 or 3 days of cefuroxime prior to PCNL between July 2017 and May 2020. Patients were further divided into four groups (Group1A = urine with positive both nitrite and white blood cell (N + WBC +) and 0-day pre-operative cefuroxime; Group1B = N + WBC + and 3-day cefuroxime; Group2A = N - WBC + and 0-day cefuroxime; Group2B = N - WBC + and 3-day cefuroxime). All patients routinely received a dose of cefuroxime 30 min prior to the surgery. In addition, Group1B were matched to the Group1A; Group2B were matched to the Group2A at a 1:1 ratio regarding stone burden, the degree of hydronephrosis, stone hardness, age and sex in a sequential order. A total of 560 patients were included (Group1A = 72; Group1B = 72; Group2A = 208; Group2B = 208). The baseline characteristics were equally distributed between the matched-pair groups. Compared to Group1B, Group1A had a significantly higher incidence of SIRS, fever, urosepsis requiring only additional antibiotics, and an increased postoperative hospitalization stay. Compared to Group2B, Group2A had similar rate of infectious complications. In addition, Group1B was associated with a significantly lower rate of positive pelvic urine culture (PUC +) than that of Group1A; whereas, there was similar rate of PUC + between Group2A and Group2B. UC-patients with N + WBC + should be treated with extended period of antibiotic administration, and a single dose of prophylactic antibiotic was sufficient for UC-patients with N - WBC + prior to PCNL. Despite UC, it is suggested to stratify pre-operative antibiotics tailored to individual patients to optimize its application.
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http://dx.doi.org/10.1007/s00240-021-01260-8DOI Listing
March 2021

High Diagnostic Utility Incorporating a Targeted Neurodegeneration Gene Panel With MRI Brain Diagnostic Algorithms in Patients With Young-Onset Cognitive Impairment With Leukodystrophy.

Front Neurol 2021 1;12:631407. Epub 2021 Feb 1.

Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore.

Leukodystrophies are a diverse group of genetic disorders that selectively involve the white matter of the brain and are a frequent cause of young-onset cognitive impairment. Genetic diagnosis is challenging. Data on the utility of incorporating brain magnetic resonance imaging (MRI) diagnostic algorithms with next-generation sequencing (NGS) for diagnosis in a real-life clinical setting is limited. We performed sequencing using a custom-designed panel of 200 neurodegeneration-associated genes on 45 patients with young-onset cognitive impairment with leukodystrophy, and classified them based on van der Knaap et al.'s MRI diagnostic algorithm. We found that 20/45 (44.4%) patients carried pathogenic variants or novel variants predicted to be pathogenic (one in , two in and 17 in ). All patients with an established genetic diagnosis had an MRI brain pattern consistent with a specific genetic condition/s. More than half (19/37, 51.4%) of patients with MRI changes consistent with vascular cognitive impairment secondary to small vessel disease (VCI-SVD) had pathogenic variants, including all patients with pathogenic (17/19, 89.5%) and variants (2/19, 11.5%). Amongst patients harboring pathogenic variants, 13/17 (76.5%) carried the p.R544C variant seen predominantly in East Asians. Anterior temporal white matter involvement was seen only in patients with pathogenic variants (6/17, 35.3%). Overall, we demonstrated a high diagnostic utility incorporating a targeted neurodegeneration gene panel and MRI-based diagnostic algorithms in young-onset cognitive impairment patients with leukodystrophy.
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http://dx.doi.org/10.3389/fneur.2021.631407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882677PMC
February 2021

Comparison of single-use and reusable flexible ureteroscope for renal stone management: a pooled analysis of 772 patients.

Transl Androl Urol 2021 Jan;10(1):483-493

Department of Urology, Xiangya Hospital, Central South University, Changsha, China.

Flexible ureteroscopy is a common therapy for patients with renal calculi. In recent years, the prevalence of single-use flexible ureteroscope (FURS) use has been on the rise. Thus, several trials have been conducted to compare the efficacy between single-use and reusable FURS. The aim of this meta-analysis was to systematically assess the effectiveness and safety of single-use reusable FURS in treating renal stones. PubMed, Web of Science, Cochrane Library and EMBASE were researched to identify relevant studies up to September 2019. Article selection was performed through the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The Newcastle-Ottawa Scale was applied to assess the methodological quality of non-randomized controlled trials, and the methodological quality of randomized controlled trials was evaluated using the Jadad scale. A total of five studies with 772 patients were included in the meta-analysis, including two randomized controlled trials, two single-centre prospective studies, and one prospective case-control trial. The pooled results showed that single-use FURS was associated with a higher stone-free rate (SFR) (OR: 1.50; 95% CI, 1.06-2.12; P=0.02) than reusable FURS. A significant difference was noted in operative time, and single-use FURS was associated with a longer operative duration (MD: 7.39 min; 95% CI, 1.75-13.03; P=0.01). No significant difference was noted in perioperative complications (OR: 0.97; 95% CI, 0.56-1.70; P=0.92). Subgroup analysis showed no significant difference in urinary tract infection (OR: 0.80; 95% CI, 0.44-1.46; P=0.46), stent migration (OR: 0.56; 95% CI, 0.19-1.65; P=0.30) or acute kidney injury (OR: 0.76; 95% CI, 0.16-3.57; P=0.73). Single-use FURS is an effective and safe alternative to reusable FURS for the management of renal stones.
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http://dx.doi.org/10.21037/tau-20-1009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844498PMC
January 2021

Value of preoperative urine white blood cell and nitrite in predicting postoperative infection following percutaneous nephrolithotomy: a meta-analysis.

Transl Androl Urol 2021 Jan;10(1):195-203

Department of Urology, Xiangya Hospital, Central South University, Changsha, China.

Background: To evaluate to what degree preoperative urine white blood cell (WBC) and urine nitrite (NIT) values are predictive of postoperative infections following percutaneous nephrolithotomy (PCNL).

Methods: A systematic literature search was performed of the PubMed, Embase, Cochrane Library, Wanfang Data, National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CSTJ or VIP) online databases to identify relevant studies that examined the predictive value of urine WBC or NIT as risk factors for post-PCNL infection, and the search was finished on February 28, 2020. Two independent reviewers screened the relevant studies, extracted necessary data from the eligible case-control studies (CCS), and assessed the quality of included studies through the Newcastle-Ottawa scale (NOS). RevMan 5.3 software and the Stata 16.0 software were used to complete the statistical analysis of data. Results are expressed as odds ratio (OR) with 95% confidence intervals (CIs).

Results: According to the statistical analysis of 12 eligible studies involving 6113 patients, positive urine WBC (WBC+: OR =3.86, 95% CI: 3.03-4.91, P<0.001) and positive NIT (NIT: OR =7.81, 95% CI: 5.44-11.21, P<0.001) in preoperative tests were identified as independent risk factors for postoperative infections following PCNL.

Conclusions: In summary, as risk factors for postoperative infections, the presence of preoperative urine WBC+ and NIT+ should be evaluated as part of clinical procedure, in order to reduce infections of PCNL.
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http://dx.doi.org/10.21037/tau-20-930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844477PMC
January 2021

Syphilitic spinal disease: an old nemesis revisited. A case series and review of literature.

Sex Transm Dis 2021 Jan 26. Epub 2021 Jan 26.

Department of Neurology, National Neuroscience Institute, Singapore Department of Radiology, Khoo Teck Puat Hospital, Singapore.

Abstract: Syphilitic spinal disease is a rare condition caused by the spirochete Treponema pallidum, either from direct spirochete involvement of the cord, or as a consequence of indirect spirochete involvement of the meninges, blood vessels, or the vertebral column. Following the introduction of penicillin therapy in the 1940s, it has become an increasingly rare condition. We report three challenging cases of syphilitic spinal disease presenting as myelopathy - one with an extra-axial gumma of tertiary syphilis causing cord compression, and two with tabes dorsalis complicated by tabetic spinal neuroarthropathy - each presenting a diagnostic dilemma to their treating physicians. We also review the literature for updates on modern investigative modalities, and discuss pitfalls physicians need to avoid in order to arrive at the diagnosis.
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http://dx.doi.org/10.1097/OLQ.0000000000001391DOI Listing
January 2021

Osteogenic Differentiation of Renal Interstitial Fibroblasts Promoted by lncRNA May Partially Contribute to Randall's Plaque Formation.

Front Cell Dev Biol 2020 11;8:596363. Epub 2021 Jan 11.

Department of Urology, Xiangya Hospital, Central South University, Changsha, China.

Background: The current belief is that Randall's plaques (RP) constitute a nidus for the formation of idiopathic calcium oxalate stones, but the upstream events in RP formation remain unclear. The present study aimed to investigate whether RP formation shares similarities with biomineralization and to illustrate the potential role played by the lncRNA in osteogenic differentiation of human renal interstitial fibroblasts (hRIFs).

Materials And Methods: Biomineralization and expression were assessed in RP, and hRIFs were isolated and induced under osteogenic conditions for further experiments. The transcription initiation and termination sites in were identified by 5' and 3' RACE. RNA immunoprecipitation assays and luciferase assays were used to validate the interactions among , and miRNAs.

Results: Upregulated expression of osteogenic markers and was observed in RP and hRIFs induced with osteogenic medium. Biomineralization in RP and calcium phosphate (CaP) deposits in induced hRIFs were further verified by electron microscopy. Furthermore, overexpression of promoted the osteogenic phenotype of hRIFs, while treatment with a miR-320a-5p mimic and knockdown of significantly suppressed the osteogenic phenotype. Further analysis showed that functioned as a competing endogenous RNA to sponge miR-320a-5p, leading to upregulation of Runx2 and thus promoting osteogenic differentiation of hRIFs.

Conclusion: Ectopic calcification and partially contributed to the formation of RP, in which might promote Runx2 expression to regulate osteogenic differentiation of hRIFs by sponging miRNA-320a-5p. The current study sheds new light on the lncRNA-directed mechanism of RP formation via a process driven by osteogenic-like cells.
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http://dx.doi.org/10.3389/fcell.2020.596363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829506PMC
January 2021

CD8 T cells predicted the conversion of common covid-19 to severe.

Sci Rep 2021 01 26;11(1):2169. Epub 2021 Jan 26.

Department of Liver Disease, The Third People's Hospital of Kunming City, Yunnan, China.

To evaluate the predictive effect of T-lymphoid subsets on the conversion of common covid-19 to severe. The laboratory data were collected retrospectively from common covid-19 patients in the First People's Hospital of Zaoyang, Hubei Province, China and the Third People's Hospital of Kunming, Yunnan Province, China, between January 20, 2020 and March 15, 2020 and divided into training set and validation set. Univariate and multivariate logistic regression was performed to investigate the risk factors for the conversion of common covid-19 to severe in the training set, the prediction model was established and verified externally in the validation set. 60 (14.71%) of 408 patients with common covid-19 became severe in 6-10 days after diagnosis. Univariate and multiple logistic regression analysis revealed that lactate (P = 0.042, OR = 1097.983, 95% CI 1.303, 924,798.262) and CD8 T cells (P = 0.010, OR = 0.903, 95% CI 0.835, 0.975) were independent risk factors for general type patients to turn to severe type. The area under ROC curve of lactate and CD8 T cells was 0.754 (0.581, 0.928) and 0.842 (0.713, 0.970), respectively. The actual observation value was highly consistent with the prediction model value in curve fitting. The established prediction model was verified in 78 COVID-19 patients in the verification set, the area under the ROC curve was 0.906 (0.861, 0.981), and the calibration curve was consistent. CD8 T cells, as an independent risk factor, could predict the transition from common covid-19 to severe.
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http://dx.doi.org/10.1038/s41598-021-81732-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838185PMC
January 2021

Clinical Images: Papulonecrotic tuberculid and Poncet disease.

ACR Open Rheumatol 2021 Feb 25;3(2):79. Epub 2021 Jan 25.

Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

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http://dx.doi.org/10.1002/acr2.11224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882537PMC
February 2021

Percutaneous nephrostomic decortication: a microinvasive surgery for posterior renal cyst.

Transl Androl Urol 2020 Dec;9(6):2764-2770

Department of Urology, Xiangya Hospital, Central South University, Changsha, China.

To assess the safety, feasibility, and efficacy of a modified process we developed in order to perform decortication surgeries for simple renal cysts through a percutaneous approach, 18 patients with simple renal cysts larger than 5 cm were treated with our new technique, from November 2016 to January 2019. All of the cysts were evaluated with ultrasonography and contrast-enhanced computed tomography. The Surgical procedure: as the standard mini-Percutaneous Nephrostomy procedure, a puncture was made directly into the cyst through the cyst roof under ultrasound guidance. After the inner cyst wall examination, the sheath was then retracted to just outside the cyst roof. The sheath together with the scope was used to detach the roof from the perirenal fat, after which the cyst roof was resected using a laser. A drain tube was left in the retroperitoneal space for 1-2 days. Subsequently, all patients were discharged 1 to 2 days post-surgery. Skin incision was less than 1 cm. No major complication was observed. The follow-up time ranges from 14 to 37 months. One case had an incompletely resected cyst with the cyst volume being decreased by more than 60%. This patient didn't receive any additional treatments during his follow-up. For all the other patients, the cysts had completely disappeared and no relapse had occurred. In conclusion, in the selected patients with a simple posterior renal cyst, our new technique is a safe and an effective option. It is also considered the least invasive decortication surgery for posterior renal cyst.
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http://dx.doi.org/10.21037/tau-20-875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807317PMC
December 2020

Successive biochar amendment affected crop yield by regulating soil nitrogen functional microbes in wheat-maize rotation farmland.

Environ Res 2021 03 30;194:110671. Epub 2020 Dec 30.

National Engineering Research Center for Wheat, State Key Laboratory of Wheat and Maize Crop Science, Henan Agricultural University, Zhengzhou, 450046, China.

Biochar has attracted increased attention because of its potential benefits for carbon sequestration, soil fertility, and contaminant immobilization. However, mechanism of long-term successive biochar amendment affected crop yield by regulating soil properties and nitrogen (N) functional microbes is still unclear by now. A field fixed experiment was carried out from 2011 to 2018 that aimed to study the effects of successive biochar on soil properties, soil nitrogen functional microbial genes, and grain yield in wheat and maize rotation farmland in Northern China. Four straw biochar treatments were tested in this study: 0 (BC0, CK), 2.25 (BC2.25), 6.75 (BC6.75), and 11.25 (BC11.25) Mg ha. The results showed that, after seven wheat-maize rotations, the total organic carbon (TOC), total N (TN), NO, available potassium (AK), and the C/N ratio in 0-20 cm topsoil were increased significantly following biochar application; however, there were no obvious differences in available phosphorus (AP) and NH among biochar treatments. Biochar also resulted in a significant increase in crop yield and NO accumulation in 0-200 cm soil layer, with the highest yield in BC6.75. Furthermore, a marked increase was found in the amoA gene abundance in topsoil; however, it decreased significantly with excessive biochar application (BC11.25). At wheat maturity, the nirS gene abundance consistently decreased following biochar application, whereas the nosZ gene abundance initially increased and then decreased (peaking in BC6.75); however, no obvious changes in the nirK gene were observed. At maize maturity, biochar significantly increased the nirS and nosZ gene abundance in topsoil, especially in BC6.75. In addition, redundancy analysis indicated that the soil moisture content, AP, AK, TN, TOC, NO, NH, pH, and C/N ratio had markedly effects on the abundance of the amoA, nirK, nirS, and nosZ genes. In general, biochar-induced alterations of soil properties resulted in changes of gene abundance of soil nitrifying and denitrifying bacteria, and eventually affecting crop yields.
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http://dx.doi.org/10.1016/j.envres.2020.110671DOI Listing
March 2021

Origin and Distribution of Large Asphaltite in South China.

ACS Omega 2020 Dec 18;5(47):30348-30355. Epub 2020 Nov 18.

Research Institute of Petroleum Exploration and Development, PetroChina, Beijing 100083, China.

Large quantities of Triassic solid asphaltite were discovered in the Guangyuan area, northwest Sichuan. The asphaltite is formed in layers with a vertical thickness between 0.3 and 2.8 m and is stably distributed with intrusive contact with surrounding rocks. This study aims on the genesis and distribution of asphaltite through trace element, biomarker, and Re-Os isotope analyses. Trace element analysis shows the enrichment of V and Cr in the asphaltite, indicating that it is derived from relatively deep hydrocarbon sources. The carbon isotope and biomarker results suggest that the asphaltite originates from Cambrian paleo reservoir. The Re-Os isotope analysis determines a formation age of 220 ± 6 Ma, which corresponds to the late Triassic, indicating the cracking of paleo reservoirs in late Triassic. Therefore, the origin of asphaltite is epigenetic-reservoir asphaltite. The generation of oil from Cambrian source rocks began at the end of Silurian and ended after Caledonian orogeny. At the end of Permian, the fracture system was well developed due to the influence of the Hercynian movement, which provided favorable conditions for the migration of Cambrian oil. By the end of Triassic, hydrocarbons generated from Cambrian source rocks were mainly distributed in fractures and reservoirs, thus forming paleo oil reservoirs. Afterward, the paleo reservoirs were adjusted to the surface or near the surface during the Indosinian movement and thus have cracked into asphaltite. The distribution of asphaltite is closely related to the tectonic activities, and the asphaltite is preferentially stored in the anticline axes, fissures, and some interlayer fracture zones.
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http://dx.doi.org/10.1021/acsomega.0c02198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711685PMC
December 2020

Suppression of osteogenic-like differentiation in human renal interstitial fibroblasts by miRNA-410-3p through MSX2.

Transl Androl Urol 2020 Oct;9(5):2082-2093

Department of Urology, Xiangya Hospital, Central South University, Changsha, China.

Background: The aim of this stay was to determine the effect of calcium ions in promoting osteogenic-like differentiation in human renal interstitial fibroblasts (hRIFs). The role of miRNA-410-3p in upregulating Msh homeobox 2 (MSX2) level in hRIFs was also investigated.

Methods: Quantitative polymerase chain reaction (qPCR) analysis was used to assess the expression levels of miRNA-410-3p in Randall's plaque (RP) and normal renal papillary (nRP) tissues. Furthermore, the expression levels of osteogenesis-related protein in the RP and nRP tissues were assessed with qPCR and immunohistochemistry (IHC). hRIFs were cultured from isolated human kidney papilla before treatment with calcium chloride or osteogenic medium, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed at 1, 5, 9, and 14 days post-treatment. Alizarin red staining was used to estimate the deposits of calcium aggregates. After the overexpression or knockdown of miRNA-410-3p, we evaluated the changes in the osteogenic-like differentiation and osteogenesis-related protein by alizarin red staining and qPCR, respectively. A binding relationship between miRNA-410-3p and MSX2 was established through a dual-luciferase reporter gene assay. Rescue experiments demonstrated that miRNA-410-3p regulated the osteogenic-like differentiation by targeting MSX2.

Results: miRNA-410-3p levels were lower in RP tissue than in control nRP tissues. qPCR and IHC showed that the level of runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN) were higher in RP tissues. The calcium deposition of hRIFs showed a time-dependent trend when treated with osteogenic medium or calcium chloride. The overexpression of miRNA-410-3p downregulated the levels of osteogenesis-related expression and attenuated mineralization. The knockdown of miRNA-410-3p yielded the opposite trend. Dual-luciferase reporter gene assay and rescue experiments indicated that miRNA-410-3p could target MSX2, while the overexpression of MSX2 reversed the effects of miRNA-410-3p on osteogenic-like differentiation.

Conclusions: The current findings suggest that calcium ions could promote the osteogenic-like differentiation of hRIFs and miRNA-410-3p regulates hRIFs osteogenic-like differentiation by inhibiting MSX2.
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http://dx.doi.org/10.21037/tau-20-607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658140PMC
October 2020

Acute radiological features facilitate diagnosis and prognosis of anti-N-methyl-d-aspartate receptor (NMDAR) and anti-voltage-gated potassium channel (VGKC) encephalitis in adults.

J Neurol Sci 2020 12 4;419:117216. Epub 2020 Nov 4.

Duke-NUS Medical School, Singapore; Department of Neuroradiology, National Neuroscience Institute, Singapore.

Background: Anti-N-methyl-d-aspartate receptor (NMDAR) and anti-voltage-gated potassium channel (VGKC) encephalitis are the commonest antibody-associated autoimmune encephalitides (AIE). Acute clinical features have been well-described, but data on the role of radiological findings in diagnosis and prognosis of AIE are limited.

Methods: Anti-NMDAR and anti-VGKC encephalitis patients from the National Neuroscience Institute were identified. We compared clinical and paraclinical features, at acute presentation and on follow-up between and within groups.

Results: Twenty-six anti-NMDAR and 11 anti-VGKC encephalitis patients were reviewed. At acute presentation, dysautonomia (57.7%) and impairment of consciousness (84.6%) occurred exclusively in anti-NMDAR encephalitis. Cerebrospinal fluid pleocytosis was more common in anti-NMDAR encephalitis (88.5% vs 20.0%, p = 0.003), while ictal electroencephalography abnormalities were more frequent in anti-VGKC encephalitis (11.5% vs 45.5%, p = 0.022). On acute imaging, leptomeningeal enhancement was seen only in anti-NMDAR encephalitis (37.5%), while hippocampal T2 hyperintensities supported the diagnosis of anti-VGKC encephalitis (63.6% vs 12.5%, p = 0.002). At follow-up (median 53.0 months, range 13.0-119.0), anti-NMDAR encephalitis patients had better modified Rankin scale scores (median 0.0 vs 3.0, p = 0.023). Relapses occurred equally in both groups. Anti-VGKC encephalitis patients with abnormal acute MRI were more likely to have poor outcomes compared to those with normal imaging (100% vs 25%, p = 0.008), whereas acute imaging features in anti-NMDAR encephalitis did not predict long-term outcomes.

Conclusions: Acute MRI findings can aid in early diagnosis and prognostication in suspected AIE. Leptomeningeal enhancement in anti-NMDAR encephalitis and hippocampal lesions in anti-VGKC encephalitis, together with typical clinical features, may allow distinction between these antibody subtypes, and specific abnormal imaging features in anti-VGKC encephalitis may be used as a prognostic marker.
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http://dx.doi.org/10.1016/j.jns.2020.117216DOI Listing
December 2020

Effect of Red Blood Cell Storage Duration on Outcomes of Isolated Traumatic Brain Injury.

Med Sci Monit 2020 Nov 7;26:e923448. Epub 2020 Nov 7.

Department of Blood Transfusion, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland).

BACKGROUND The aim of this study was to investigate the effects of red blood cell (RBC) storage duration on the outcomes of adult isolated traumatic brain injury (iTBI) patients after transfusion. MATERIAL AND METHODS A total of 1252 adult iTBI patients who received the fresh RBCs (stored for £14 days) or old RBCs (stored for >14 days) were finally enrolled in this study. The primary outcome was 90-day mortality. The secondary outcomes were in-hospital mortality, nosocomial infection, and complications. RESULTS By 90 days after RBC transfusion, 89 patients (17.0%) had died in the fresh RBC group, and 107 had died (14.7%) in the old RBC group, with no significant difference in 90-day mortality between the 2 groups (OR=1.192, 95% CI: 0.877-1.620, P=0.261). According to ISS score, no differences were discovered in mild injury (OR=1.079, 95% CI: 0.682-1.707, P=0.746), severe injury (OR=1.055, 95% CI: 0.634-1.755, P=0.838), and more severe injury (OR=1.940, 95% CI: 0.955-3.943, P=0.064). For GCS score, there were no differences in mild injury (OR=1.546, 95% CI: 0.893-2.676, P=0.118), moderate injury (OR=0.965, 95% CI: 0.616-1.513, P=0.877), and severe injury (OR=1.332, 95% CI: 0.677-2.620, P=0.406). We also observed no significant differences in secondary outcomes. CONCLUSIONS Use of old RBCs did not increase the 90-day mortality in adult iTBI patients.
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http://dx.doi.org/10.12659/MSM.923448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657062PMC
November 2020

Facial Nerve Involvement Accompanying Optic Neuritis Secondary to Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder.

J Neuroophthalmol 2020 Oct 28. Epub 2020 Oct 28.

Department of Neurology (ZC, MS), National Neuroscience Institute, Singapore; and Department of Neuro-Ophthalmology (JLL), Singapore National Eye Centre, Singapore.

We present the first reported case of facial nerve involvement accompanying an optic neuritis in myelin oligodendrocyte glycoprotein antibody-associated disorder.
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http://dx.doi.org/10.1097/WNO.0000000000001145DOI Listing
October 2020

Ubiquitin-mediated receptor degradation contributes to development of tolerance to MrgC agonist-induced pain inhibition in neuropathic rats.

Pain 2021 04;162(4):1082-1094

Department of Anesthesiology and Critical Care Medicine, the Johns Hopkins University, School of Medicine, Baltimore, MD, United States.

Abstract: Agonists to subtype C of the Mas-related G-protein-coupled receptors (MrgC) induce pain inhibition after intrathecal (i.t.) administration in rodent models of nerve injury. Here, we investigated whether tolerance develops after repeated MrgC agonist treatments and examined the underlying mechanisms. In animal behavior studies conducted in male rats at 4 to 5 weeks after an L5 spinal nerve ligation (SNL), the ability of dipeptide MrgC agonist JHU58 (0.1 mM, 10 μL, i.t.) to inhibit mechanical and heat hypersensitivity decreased after 3 days of treatment with a tolerance-inducing dose (0.5 mM, 10 μL, i.t., twice/day). In HEK293T cells, acute treatment with JHU58 or BAM8-22 (a large peptide MrgC agonist) led to MrgC endocytosis from the cell membrane and later sorting to the membrane for reinsertion. However, chronic exposure to JHU58 increased the coupling of MrgC to β-arrestin-2 and led to the ubiquitination and degradation of MrgC. Importantly, pretreatment with TAK-243 (0.2 mM, 5 μL, i.t.), a small-molecule inhibitor of the ubiquitin-activating enzyme, during tolerance induction attenuated the development of tolerance to JHU58-induced inhibition of mechanical and heat hypersensitivity in SNL rats. Interestingly, morphine analgesia was also decreased in SNL rats that had become tolerant to JHU58, suggesting a cross-tolerance. Furthermore, i.t. pretreatment with TAK-243, which reduced JHU58 tolerance, also attenuated the cross-tolerance to morphine analgesia. These findings suggest that tolerance can develop to MrgC agonist-induced pain inhibition after repeated i.t. administrations. This tolerance development to JHU58 may involve increased coupling of MrgC to β-arrestin-2 and ubiquitin-mediated receptor degradation.
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http://dx.doi.org/10.1097/j.pain.0000000000002119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969388PMC
April 2021

The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother-neonate cohort study.

Lancet Infect Dis 2021 03 5;21(3):418-426. Epub 2020 Oct 5.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China; Key Laboratory of Surveillance and Early Warning on Infectious Disease, Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

Background: Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease.

Methods: We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests.

Findings: Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection.

Interpretation: EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age.

Funding: National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S1473-3099(20)30480-1DOI Listing
March 2021

Calcium imaging in population of dorsal root ganglion neurons unravels novel mechanisms of visceral pain sensitization and referred somatic hypersensitivity.

Pain 2021 04;162(4):1068-1081

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, United States.

Abstract: Mechanisms of visceral pain sensitization and referred somatic hypersensitivity remain unclear. We conducted calcium imaging in Pirt-GCaMP6s mice to gauge responses of dorsal root ganglion (DRG) neurons to visceral and somatic stimulation in vivo. Intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colonic inflammation and increased the percentage of L6 DRG neurons that responded to colorectal distension above that of controls at day 7. Colorectal distension did not activate L4 DRG neurons. TNBS-treated mice exhibited more Evans blue extravasation than did control mice and developed mechanical hypersensitivity in low-back skin and hind paws, which are innervated by L6 and L4 DRG neurons, respectively, suggesting that colonic inflammation induced mechanical hypersensitivity in both homosegmental and heterosegmental somatic regions. Importantly, the percentage of L4 DRG neurons activated by hind paw pinch and brush stimulation and calcium responses of L6 DRG neurons to low-back brush stimulation were higher at day 7 after TNBS than those in control mice. Visceral irritation from intracolonic capsaicin instillation also increased Evans blue extravasation in hind paws and low-back skin and acutely increased the percentage of L4 DRG neurons responding to hind paw pinch and the response of L6 DRG neurons to low-back brush stimulation. These findings suggest that TNBS-induced colitis and capsaicin-induced visceral irritation may sensitize L6 DRG neurons to colorectal and somatic inputs and also increase the excitability of L4 DRG neurons that do not receive colorectal inputs. These changes may represent a potential peripheral neuronal mechanism for visceral pain sensitization and referred somatic hypersensitivity.
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http://dx.doi.org/10.1097/j.pain.0000000000002096DOI Listing
April 2021