bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-responses of O-methyltransferase genes to salt stress and fiber development of Gossypium species
Authors: Hafeez Abdul , Gě Qún , Zhāng Qí , Lǐ Jùnwén , Gōng Jǔwǔ , Liú Ruìxián , Shí Yùzhēn , Shāng Hǎihóng , Liú Àiyīng , Iqbal Muhammad S. , Dèng Xiǎoyīng , Razzaq Abdul , Ali Muharam , Yuán Yǒulù , Wankui Gong
Published: October 2020

Background: O-methyltransferases (OMTs) are an important group of enzymes that catalyze the transfer of a methyl group from S-adenosyl-L-methionine to their acceptor substrates. OMTs are divided into several groups according to their structural features. In Gossypium species, they are involved in phenolics and flavonoid pathways. Phenolics defend the cellulose fiber from dreadful external conditions of biotic and abiotic stresses, promoting strength and growth of plant cell wall. Results: An OMT gene family, containing a total of 192 members, has been identified and characterized in three main Gossypium species, G. hirsutum, G. arboreum and G. raimondii. Cis-regulatory elements analysis suggested important roles of OMT genes in growth, development, and defense against stresses. Transcriptome data of different fiber developmental stages in Chromosome Substitution Segment Lines (CSSLs), Recombination Inbred Lines (RILs) with excellent fiber quality, and standard genetic cotton cultivar TM-1 demonstrate that up-regulation of OMT genes at different fiber developmental stages, and abiotic stress treatments have some significant correlations with fiber quality formation, and with salt stress response. Quantitative RT-PCR results revealed that GhOMT10_Dt and GhOMT70_At genes had a specific expression in response to salt stress while GhOMT49_At, GhOMT49_Dt, and GhOMT48_At in fiber elongation and secondary cell wall stages. Conclusions: Our results indicate that O-methyltransferase genes have multi-responses to salt stress and fiber development in Gossypium species and that they may contribute to salt tolerance or fiber quality formation in Gossypium.
Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma
Authors: Wei Qing , Liao Jing , Jiang Min , Liu Jing , Liang Xiuan , Nong Guangmin
Published: October 2020

Background: The pathogenetic mechanisms of neutrophilic asthma are not well understood now. Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma.Methods: Twenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA, n=12) group, neutrophilic asthma (NA, n=10) group and paucigranulocytic asthma (PGA, n=6) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC, n=10) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of retinoic acid-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA.Results: The percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other.Conclusions: Both Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.
Clinical analysis of pain after transvaginal mesh surgery in patients with pelvic organ prolapse
Authors: Shi Chang , Zhao Ying , Hu Qing , Gong Runqi , Yin Yitong , Xia Zhijun
Published: October 2020

Background: The purpose of this study was to investigate the relevant factors of pain after transvaginal mesh (TVM) surgery for the treatment of pelvic organ prolapse and to analyse the management and relief of the pain.Methods: A multicentre retrospective study of a clinical database of patients who underwent TVM surgery was conducted, and pain related aspects were analysed.Results: A total of 1855 patients were included in the study. We divided the patients into two groups: pain-free (1805 patients) and pain (50 patients) group. The incidence of pain after TVM surgery was 2.70%, with a median occurrence time of 7.5 months. Pain mainly involved the vagina, perineum, buttocks, groin, inner thighs, and lower abdomen. Excessive intraoperative blood loss (OR=1.284, 95%CI 0.868-2.401) and postoperative anatomic failure (OR=1.577, 95%CI 0.952-3.104) were analysed as risk factors with statistical significance. Mesh exposure rate in the pain group was 38%, showing a significant difference between the groups (P<0.01). Forty patients underwent non-surgical treatment, with a relief rate of 40.0%, 33 patients received surgical treatment, 15 underwent partial mesh removal, and 18 underwent complete mesh removal, with a relief rate of 84.8%. The total relief rate was 88% within all 50 patients suffering from pain.Conclusions: Excessive intraoperative bleeding and unsatisfactory postoperative anatomic outcomes can increase the risk of postoperative pain; mesh exposure is also associated with the pain. Most patients can get pain relief with proper management, more than half of whom may need mesh removal with differing approach.
Appropriate insertion point for percutaneous pedicle screw placement in the lumbar spine using c-arm fluoroscopy: a cadaveric study 
Authors: Xu Wei-Xing , Ding wei-guo , Xu Bin , Hu Tian-Hong , Sheng Hong-Feng , Zhu Jia-Fu , Zhu Xiao-Long
Published: October 2020

Background: We studied the characteristics and regularity of appropriate insertion points for percutaneous pedicle screw placement in the lumbar spine using C-arm X-ray fluoroscopy. The purpose of this study was to improve the accuracy of percutaneous pedicle screw placement and reduce the incidence of superior-level facet joint violation. Methods: Six normal spinal specimens were included. Three different methods for placing percutaneous pedicle screws in the lumbar spine were applied, including the Roy-Camille method, Magerl method and Weinstein method. The relationships among the insertion point, pedicle projection and proximal facet joint on C-arm X-ray films were studied. The projection morphology of the vertebral pedicle in different segments of the lumbar spine was observed. The relationship between the outer edge of the pedicle projection and the outer edge of the cranial articular process was also studied. The distance between the insertion point and the facet joint (M1), the distance between the insertion point and outer edge of the cranial articular process (M2), and the distance between the insertion point and the projection center of the pedicle (M) were measured. Results: In this study, we found that the projection shape of the vertebral pedicle differed across segments of the lumbar spine: the shape for L1-L3 was oval, and that for L4-L5 was round. The radiographic study showed that the outer edge of the cranial articular process was located on the lateral side of the outer edge of the pedicle projection and did not overlap with the pedicle projection. M for the Weinstein group was larger than that for the Roy-Camille group (P < 0.05). M1 for the Weinstein group was larger than that for the Roy-Camille and Magerl groups (P < 0.05). M2 for the Roy-Camille group was negative, M2 for the Magerl group was 0, and M2 for the Weinstein group was positive. Conclusion: Under C-arm X-ray fluoroscopy, we were able to accurately identify the characteristics and regularity of the appropriate insertion point for percutaneous pedicle screw placement in the lumbar spine, which was important for improving the accuracy of percutaneous pedicle screw placement and reducing the incidence of superior-level facet joint violation.
Percutaneous Endoscopic Unilateral Laminotomy and Bilateral Decompression under 3D Real-Time Image-Guided Navigation for Spinal Stenosis in Degenerative Lumbar Kyphoscoliosis Patient: An Innovative Preliminary Study
Authors: Ho Tsung-Yu , Lin Chung-Wei , Chang Chien-Chun , Chen Hsien-Te , Chen Yen-Jen , Lo Yuan-Shun , Hsiao Pan-Hsuan , Chen Po-Chen , Lin Chih-Sheng , Tsou Hsi-Kai
Published: October 2020

Background: The aim of this study is to introduce a new method of percutaneous endoscopic decompression under 3D real-time image-guided navigation for spinal stenosis in degenerative kyphoscoliosis patients without instability or those who with multiple comorbidities. Decompression alone using endoscope for kyphoscoliosis patient is technical demanding and may result in unnecessary bone destruction leading to further instability. The O-arm/StealthStation system is popular for its ability to provide automated registration with intraoperative, postpositioning computed tomography (CT) which results in superior accuracy in spine surgery.Methods: In this study, we presented four cases. All patients were over seventy years old female with variable degrees of kyphoscoliosis and multiple comorbidities who could not endure major spine fusion surgery. Percutaneous endoscopic unilateral laminotomy and bilateral decompression under 3D real-time image-guided navigation were successfully performed. Patients’ demographics, image study parameters, and outcome measurements including pre- and post-operative serial Visual analog scale (VAS), and Oswestry Disability Index (ODI) were well documented. The follow-up time was one year.Results: Pre- and post-operative MRI showed average dural sac cross sectional area (DSCSA) improved from 81.62 (range 67.34-89.07) to 153.27 (range 127.96-189.73). Preoperative neurological symptoms including radicular leg pain improved postoperatively. The mean ODI (%) were 85 (range 82.5-90) at initial visit, 35.875 (range 25-51) at 1 month post-operatively, 26.875 (range 22.5-35) at 6 months post-operatively and 22.5 (range 17.5-30) at 12 months post-operatively (p <0.05). The mean VAS score were 9 (range 8-10) at initial visit, 2.25 (range 2-3) at 1 month post-operatively, 1.75 (range 1-2) at 6 months post-operatively and 0.25 (range 0-1) at 12 months post-operatively (p <0.05). There was no surgery-related complication.Conclusions: To the best of our knowledge, this is the first preliminary study of percutaneous endoscopic laminotomy under O-arm navigation with successful outcomes. The innovative technique may serve as a promising solution in treating spinal stenosis patients with lumbar kyphoscoliosis and multiple comorbidities.
Clinical prediction score for diagnosing non-diabetic renal disease in patients with type 2 diabetes mellitus: a cohort study
Authors: Surinrat Ekkapong , Eiamsitrakoon Thanee , Krisanapan Pajaree , Chatkrailert Aphichat , Yoosabai Anake , Traitanon Opas , Tasanarong Adis , Charoenpitakchai Mongkon , Tantiyavarong Pichaya , Surinrat Ekkapong
Published: October 2020

BackgroundWhen non-diabetic renal disease (NDRD) is suspected, kidney biopsy is used for definite diagnosis; however, this is not always easily available and may lead to complications. A clinical prediction score may help selecting appropriate patients for kidney biopsy. MethodsA retrospective cohort study was conducted in type 2 diabetes mellitus (T2DM) patients with atypical features of diabetic nephropathy (DN), who had kidney biopsy at Thammasat University Hospital from 2011-2019. We divided patients into NDRD alone, coexisting NDRD and DN, and DN alone, confirmed by pathological diagnosis. We developed a clinical prediction score by weighing coefficients of predictors in a multivariable logistic model. Internal validation was performed with bootstrapping.ResultsWe included 81 patients: 28 (34%) had NDRD alone, 15 (18%) had coexisting NDRD and DN, and 38 (41%) had DN alone. Primary membranous nephropathy, primary focal and segmental glomerulosclerosis (FSGS), and secondary FSGS were prevalent in any NDRD. Absence of diabetic retinopathy (DR) showed a significant association with any NDRD (OR 3.72; 95% CI, 1.28-10.8; p=0.02). The prediction score, AUC of 0.75 (95% CI, 0.63-0.86), had four predictors: duration of DM <10 years, eGFR >30 ml/min/1.73m2, HbA1c <8%, and absence of DR. Higher scores were associated with higher probability of NDRD.ConclusionsThis clinical prediction score appears to be a useful tool to determine NDRD probability. T2DM patients with atypical presentation of DN with lower scores (0-2) may defer kidney biopsy.
Exploring natural allelic variations of the β-triketone herbicide resistance gene HIS1 for application in indica rice and particularly in two-line hybrid rice
Authors: Lv Qiming , Zhang Xiuli , Yuan Dingyang , Huang Zhiyuan , Peng Rui , Peng Jiming , Li Zuren , Tang Li , Liu Ducai , Zhou Xiaomao , Wang Lifeng , Pan Lang , Shao Ye , Mao Bigang , Xin Yeyun , Zhu Lihuang , Zhao Bingran , Bai Lianyang
Published: October 2020

Background: Benzobicyclon (BBC) is a β-triketone herbicide (bTH) used in rice paddy fields. It has the advantages of high efficiency, low toxicity, high crop safety, and good environmental compatibility, and shows efficacy against paddy weeds resistant to other types of herbicides. However, as some important indica rice varieties are susceptible to BBC, BBC is currently only registered and applied in japonica rice cultivation areas.Results: By analyzing haplotypes of the bTHs broad-spectrum resistance gene HIS1 and phenotypes for BBC in 493 major indica rice accessions in China, we identified a novel non-functional allelic variant of HIS1 in addition to the previously reported 28-bp deletion. Through detection with markers specific to the two non-functional mutations, it was clear that 25.4% of indica conventional varieties, 59.9% of restorers, and 15.9% of sterile lines were susceptible to BBC. In addition, due to natural allelic variations of the HIS1 gene in the sterile and restorer lines, some two-line hybrid sterile lines were sensitive to bTHs, and the corresponding restorers were resistant. We showed the potential effectiveness of using bTHs to address the issue of two-line hybrid rice seed purity stemming from the self-crossing of sterile lines during hybrid rice seed production. Finally, allelic variations of the HIS1 gene may also play an important role in the mechanized seed production of hybrid rice.Conclusions: Our findings offer guidance for the application of BBC in indica rice areas and provide a non-transgenic approach to address the seed purity issue of two-line hybrid rice.
Comparison of the effectiveness and safety of intravenous and topical regimens of tranexamic acid in complex tibial plateau fracture: a retrospective study
Authors: Wang Zhimeng , Lu Yao , Wang Qian , Song Leilei , Ma Teng , Ren Cheng , Li Zhong , Yang Jiarui , Zhang Kun , Zhang Bing
Published: October 2020

Background Previous studies have demonstrated the effectiveness and safety of tranexamic acid (TXA) in orthopedic surgery. However, no study has investigated TXA in complex tibial plateau fracture surgery. Therefore, the purpose of this study was to confirm the safety and effectiveness of i.v. (intravenous) TXA and topical TXA.Material and methods This was a retrospective analysis of prospectively collected data. The control group received an equal amount of placebo (physiological saline solution); the i.v. group received 1.0 g TXA by intravenous injection before the tourniquet was inflated and before the surgical incision was closed, and the topical group received 3.0 g TXA in 75 mL of physiological saline solution 5 minutes prior to the final tourniquet release. Perioperative blood loss, vascular events, wound complications, and adverse reactions were compared among the three groups. The pain, knee function, and quality of life (QoL) assessments were based on their corresponding scoring systems.Results Baseline data were comparable for all groups. The i.v. group showed the best results for total blood loss (TBL) and hidden blood loss (HBL) (424.5 ± 49.4 mL and 219.3 ± 33.4 mL, respectively, all P values < 0.001). Patients in the i.v. group had lesser real Hb decrease than those in the control group (0.9 vs 1.5, P＜0.001) and topical group (0.9 vs 1.2, P = 0.026). The blood coagulation level as measured using fibrinolysis (D-dimer) was lower in the i.v. group than in the control and topical groups on POD1 and POD3; however, this difference was not significant; the fibrin-degradation products also showed a similar trend. Patients in the topical group experienced less pain than those in the control group on POD2, POD4, and PO6W. The VAS pain score was 3.6 vs. 4.4 (POD2, P＜0.05), 2.8 vs 3.3 (POD4, P＜0.05), and 2.1 vs. 2.6 (PO6W, P＜0.001) in the topical group vs control group, respectively. No significant differences were identified in vascular events, wound complications, adverse reactions, knee function, and QoL among the three groups.Conclusion To our knowledge, this is the first study that showed both i.v. TXA and topical TXA are safe and effective for complex tibial plateau fractures. The i.v. regimen effectively reduced blood loss during the perioperative period, whereas patients under the topical regimen had less vascular events, wound complications, and a lower incidence of adverse reactions compared to those in the i.v. group.
hPMSCs protects against D-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling 
Authors: Xiong Yanlian , Wang Yueming , Zhang Jiashen , Zhao Nannan , Zhang Hengchao , Zhang Aiping , Zhao Dongmei , Yu Zhenhai , Yin Yancun , Song Lele , Xiong Yanlei , Luan Xiying
Published: October 2020

Background: Mesenchymal stem cells (MSCs) was considered as regenerative therapeutic approach in both acute and chronic diseases. However, whether MSCs regulate the antioxidant metabolism of CD4+ T cells and weaken immunosenescence remains unclear. Here, we reported the protective effects of hPMSCs in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model.Methods: In vivo study, 40 male C57BL/6 mice (8 weeks) were randomly divided into four groups: control group, D-gal group, hPMSC group and PBS group. In in vitro experiment, human naive CD4+ T (CD4CD45RA) cells were prepared using a naive CD4+ T cell isolation kit II and pretreated with the Akt inhibitor LY294002 and Nrf2 inhibitor ML385. Then, isolated naive CD4+ T cell were cocultured with hPMSCs for 72 h in the absence or presence of anti-CD3/CD28 Dynabeads and IL-2 as a mitogenic stimulus. Intracellular ROS changes were detected by flow cytometry. The activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase were measured by colorimetric analysis. The senescent T cells were detected SA-β-gal stain. The expression of aging related proteins were detected by Western blotting, RT-PCR and confocal microscopy.Results: We found that hPMSC treatment markedly decreased the ROS level, SA-β-gal positive cells number, senescence-associated secretory phenotype (IL-6 and OPN) expression and aging-related protein (P16 and P21) expression in senescent CD4+ T cells. Furthermore, hPMSC treatment effectively upregulated Nrf2 nuclear translocation and the expression of downstream target genes (HO-1, CAT, GCLC and NQO1) in senescent CD4+ T cells. Moreover, in vitro studies revealed that hPMSCs attenuated CD4+ T cell senescence by upregulating the Akt/GSK-3β/Fyn pathway to activate Nrf2 functions. Conversely, the antioxidant effects of hPMSCs were blocked by the Akt inhibitor LY294002 and Nrf2 inhibitor ML385 in senescent CD4+ T cells.Conclusions: Our results indicate that hPMSCs attenuate D-gal induced CD4+ T cell senescence by activating Nrf2-mediated antioxidant defenses and that upregulation of Nrf2 by hPMSCs is regulated via the Akt/GSK-3β/Fyn pathway.
Development and launch of the first Obstetrics and Gynaecology Master of Medicine residency training programme in Botswana
Authors: Luckett Rebecca , Nassali Mercy , Melese Tadele , Moreri-Ntshabele Badani , Moloi Thabo , Hofmeyr Justus , Chobanga Kudra , Masunge Japhter , Makhema Joe , Pollard Maisie , Ricciotti Hope , Ramogola-Masire Doreeen , Bazzett-Matabele Lisa
Published: October 2020

Background: Sub-Saharan Africa (SSA) faces a severe shortage of Obstetrician Gynaecologists (OBGYNs). While the Lancet Commission for Global Surgery recommends 20 OBGYNs per 100,000 population, Botswana has only 40 OBGYNs for a population of 2.3 million. We describe the development of the first OBGYN Master of Medicine (MMed) training programme in Botswana to address this human resource shortage.Methods: We developed a 4-year OBGYN MMed programme at the University of Botswana (UB) using the Kern's approach. In-line with UB MMed standards, the programme includes clinical apprenticeship training complemented by didactic and research requirements. We benchmarked curriculum content, learning outcomes, competencies, assessment strategies and research requirements with regional and international programmes. We engaged relevant local stakeholders and developed international collaborations to support in-country subspecialty training.Results: The OBGYN MMed curriculum was completed and approved by all relevant UB bodies within ten months during which time additional staff were recruited and programme financing was assured. The programme was advertised immediately; 26 candidates applied for four positions, and all selected candidates accepted. The programme was launched in January 2020 with government salary support of all residents. The clinical rotations and curricular development have been rolled out successfully. The first round of continuous assessment of residents was performed and internal programme evaluation was conducted. The national accreditation process was initiated.Conclusion: Training OBGYNs in-country has many benefits to health systems in SSA. Curricula can be adjusted to local resource context yet achieve international standards through thoughtful design and purposeful collaborations.
The Relationship between QT Interval Indices with Cardiac Autonomic Neuropathy in Diabetic Patients- A casecontrol_ study
Authors: vasheghani maryam , Sarvghadi Farzaneh , Beyranvand Mohammad Reza , Emami Habib
Published: October 2020

Background: Long QT interval (QT) and abnormal QT dispersion (QTd) are associated with sudden death. The relationship between cardiac autonomic neuropathy (CAN) and QT indices in type 2 diabetic patients were investigated. Methods: Totally 130 diabetic subjects (mean age 50.87 ± 13.9 years) were included (70 individuals with and 60 individuals without CAN). All participants had sinus cardiac rhythm. The patients who had diseases or take drugs that cause orthostatic hypotension (OH), cardiac arrhythmia and QT prolongation were excluded. After interview and examination, standard and continuous ECG was taken in supine position with deep breathing and standing up position. CAN diagnosis was based on Ewing’s tests. QT, QT corrected (QTc), minimum QT (QT min), maximum QT (QT max) and mean ± SD of QT (QT mean) and QTd were assessed from standard ECG. QTc was calculated by Bazett’s formula from V2 lead. QTc > 440 msec in men and QTc > 0.46 msec in women and QTd > 80 msec were considered abnormal.Results: In patients with CAN, 21.5% were symptomatic. The prevalence of abnormal QTc and QTd was 11.3% and 28.7%, respectively. There was no significant difference between the patients with or without CAN in terms of long QTc and abnormal QTd. However, the mean ± SD of QT max, QT mean and QTd was higher in the patients with CAN (P value <0.03). The used cut points for QTc and QTd have high specificity (79% for both) and low sensitivity (30% and 37%, respectively). To use QTc and QTd as screening test for CAN in T2DM patients, the cutoff points 380 and 550 msec are suggested, respectively. Conclusion: The prevalence of asymptomatic CAN was 3.7 times that of symptomatic CAN. In patients with CAN the QT max, QT mean and QTd were higher than those without CAN .There was no association between CAN and long QTc and abnormal QTd.
Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression
Authors: Sun Guangli , Li Zheng , He Zhongyuan , Wang Weizhi , Wang Sen , Zhang Xing , Cao Jiacheng , Xu Penghui , Wang Haixiao , Huang Xiaoxu , Xia Yiwen , Lv Jialun , Xuan Zhe , Jiang Tianlu , Fang Lang , Yang Jing , Zhang Diancai , Xu Hao , Xu Ze-Kuan
Published: October 2020

Background: Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). The poor prognosis of GC patients is partially due to the development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated.Methods: RNA sequencing was used to identify the differentially expressed circRNAs between CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and luciferase reporter assays were performed to confirm the interactions among circMCTP2, miR-99a-5p, and myotubularin-related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM).Results: CircMCTP2 was downregulated in CDDP-resistant GC cells and tissues compared to CDDP-sensitive GC cells and tissues. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited proliferation while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 was also found to reduce autophagy in CDDP-resistant GC cells. MiR-99a-5p was verified to be sponged by circMCTP2. Inhibition of miR-99a-5p could sensitize GC cells to CDDP. MTMR3 was confirmed to be a direct target of miR-99a-5p. Knockdown of MTMR3 reversed the effects of circMCTP2 on the proliferation, apoptosis and autophagy of CDDP-resistant GC cells. CircMCTP2 was also confirmed to inhibit CDDP resistance in vivo in a nude mouse xenograft model.Conclusions: CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.
The effect of preoperative chemotherapy on liver regeneration after portal vein embolization/ligation or liver resection in patients with colorectal liver metastasis: a systematic review protocol
Authors: Pavel Mihai-Calin , Casanova Raquel , Estalella Laia , Memba Robert , Llàcer-Millán Erik , Achalandabaso Mar , Julià Elisabet , Geoghegan Justin , Jorba Rosa
Published: October 2020

Introduction: Liver resection (LR) in patients with liver metastasis from colo-rectal cancer remains the only curative treatment. Perioperative chemotherapy improves prognosis of these patients. However, there are concerns regarding the effect of preoperative chemotherapy on liver regeneration, which is a key event in avoiding liver failure after LR. The primary objective of this systematic review is to assess the effect of neoadjuvant chemotherapy on liver regeneration after (LR) or portal vein embolization (PVE) in patients with liver metastasis from colo-rectal cancer. The secondary objectives are to evaluate the impact of the type of chemotherapy, number of cycles and time between end of treatment and procedure (LR or PVE) and to investigate whether there is an association between degree of hypertrophy and postoperative liver failure.Methods: The design of this systematic review will follow the current recommendations of PRISMA. After an exhaustive literature search with pre-established criteria, two researchers will individually screen the identified records, according to a list of inclusion and exclusion criteria. Primary outcome will be future liver remnant regeneration rate. All data will be registered in a predesigned database. In the event of a substantial heterogeneity of selected articles, a narrative systematic review will be performed.Discussion: The results of this systematic review may help to better identify the patients affected by liver metastasis that could present low regeneration rates after neoadjuvant chemotherapy. These patients are at risk to develop liver failure after extended hepatectomies and therefore are not good candidates for such aggressive procedures.Systematic Review Registration: PROSPERO registration number: CRD42020178481 (July 5th 2020).
Regular consumption of soft drinks is associated with type 2 diabetes incidence in Mexican adults: findings from a prospective cohort study.
Authors: Torres-Ibarra Leticia , Rivera-Paredez Berenice , Hernández-López Rubí , Canto-Osorio Francisco , Sánchez-Romero Luz María , Lopez-Olmedo Nancy , González-Morales Romina , Ramírez Paula , Salmerón Jorge , Barrientos-Gutiérrez Tonatiuh
Published: October 2020

Background: Although high consumption of soft drinks has been associated with excess of type 2 diabetes risk, the strength of this association in the Mexican population, where a type 2 diabetes genetic susceptibility has been well established, has been scarcely studied. This study aimed to estimate the risk of type 2 diabetes due to soft drinks consumption in a cohort of Mexicans. Methods: We used data on 1,445 participants from the Health Workers Cohort Study, a prospective cohort conducted in Cuernavaca, Mexico. Soft drinks consumption was assessed with a semi-quantitative 116-item food frequency questionnaire. Incident type 2 diabetes was defined as self-report of physician-diagnosed type 2 diabetes, fasting glucose >126 mg/dl, or hypoglycemic medication at any examination. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models.Results: With a total of 9,526.2 person-years of follow-up, 109 incident cases of type 2 diabetes were observed. Type 2 diabetes incidence rate was 7.6, 11.0, and 17.1 per 1,000 person-years across levels of soft drinks consumption of <1, 1-4, and ³5 servings/week, respectively (p<0.001 for trend). The intake of ≥5 soft drinks/week was significantly associated with an increased risk of type 2 diabetes (HR 1.9 95% CI:1.0-3.5) compared with consumption of <1/week (p-trend=0.040). The HR was attenuated by further adjustment for body mass index (HR 1.5 95%CI:0.8-2.8) and abdominal obesity (HR 1.6 95%CI:0.8-3.0). Conclusions: The consumption of soft drinks was associated with a higher risk of type 2 diabetes in a cohort of Mexican adults. Our results further support recommendations to limit soft drinks intake to address the growing diabetes epidemic in Mexico.
Circ-CCDC66 upregulates REXO1 expression to aggravate cervical cancer progression via restraining miR-452-5p
Authors: Zhang Yan , Li Xing , Zhang Jun , Mao Lin
Published: October 2020

Background: Cervical cancer is one most common cancer types among females over the world. While its underlying mechanisms remain unclear. Circ-CCDC66 has been revealed to participate in multiple biological functions, and contribute to various diseases’ progression. In the current study, we aimed to demonstrate the role of circ-CCDC66 in cervical cancer progression. Methods: Real-time quantitative PCR (RT-qPCR) was conducted to measure the expression of circ-CCDC66, miR-452-5p, and REXO1 mRNA. Cell fractionation assay and RNA fluorescence in situ hybridization (FISH) were performed to locate circ-CCDC66 in cells. Cell account kit 8 (CCK-8) was used to detect cell proliferation ability. Transwell assay was applied to evaluate cell migration or invasion ability. Bioinformatics analysis, biotinylated RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assays were conducted to assess the association between miR-452 and circ-CCDC66 or REXO1. Western blot was applied to measure the protein expression of REXO1. The animal tumor model was used to assess the effect of circ-CCDC66 in vivo . Results: The expression of circ-CCDC66 was upregulated in cervical cancer tumor tissues in comparison with normal tissues, and correlated with later tumor stage and larger tumor size. Downregulated circ-CCDC66 inhibited cervical cancer cell proliferation, migration, and invasion. Circ-CCDC66 was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. MiR-452-5p directly targeted to REXO1. Circ-CCDC66 regulated REXO1 expression to modulate cervical cancer progression via miR-452-5p. Moreover, downregulated circ-CCDC66 was found to suppress tumor growth in vivo. Conclusion: Our results demonstrated the role of circ-CCDC66/miR-452-5p/REXO1 axis in cervical cancer progression, we might provide novel therapeutic targets for cervical cancer clinical intervention.
Screening of subclinical P300 event-related potentials changes in childhood acute lymphoblastic leukemia survivors: comparison of different treatment protocols.
Authors: Kroczka Slawomir , Stepien Konrad , Skoczen Szymon
Published: October 2020

Background: Modern treatment protocols in childhood acute lymphoblastic leukemia (ALL) resulted in high cure rate and improved long-term survival. However, due to their high intensity, they are also associated with many side effects, including central nervous system toxicity. The aim of our study was to evaluate the use of screening of subclinical P300 event-related potentials changes in childhood ALL survivors.
Methods: A group of 136 patients, 66 males (48.5%), aged 4.9 to 27.9 years who have completed ALL therapy, were screened for subclinical P300 potentials changes. ALL therapy was conducted according to modified New York (NY) (30 patients) and subsequent revisions of modified Berlin-Frankfurt-Münster (BFM): previous BFM protocols (pBFM) (32 patients) and BFM95 (74 patients). The control group consisted of 58 patients, 34 males (58.6%), aged 6 to 17 years after a syncope episode (n=29) as well as healthy subjects (n=29).
Results: The total group of ALL survivors had significantly prolonged the mean latency of P300 (331.31±28.71 vs 298.14±38.76 ms, P<0.001) and reaction time (439.51±119.86 vs 380.11±79.94 ms, P=0.002) compared to the control group. Abnormalities in endogenous evoked potentials were observed in 10 (33.33%) NY, 5 (15.63%) pBFM and 21 (28.38%) BFM95 patients. The mean latency time was significantly longer compared to the control group in all analyzed protocols and the highest values were observed in pBFM patients (NY: 329.13±28.07 ms, P=0.001; pBFM: 332.97±23.97 ms, P<0.001; BFM95: 331.47±31.05 ms, P<0.001). The reaction time was similarly prolonged compared to the control group. The largest and also significant prolongation was recorded in the NY group (461.8±140.3 vs 380.1±78.04 ms, P=0.039).
Analyzing the effect of radiotherapy on P300 potentials, a significantly higher frequency of prolonged reaction time in non-irradiated BFM95 patients was found (21.62 vs 15.85%, P=0.007). Radiotherapy methods used in NY and pBFM protocols have also significantly reduced the P300 wave amplitude (mean values: 10.395±5.727 vs 12.739±6.508 ms, P=0.027).
Conclusions: Endogenous P300 event-related potentials may be useful in screening assessment of late subclinical cognitive changes in ALL survivors. The type of treatment protocol significantly modulates the individual parameters of the registered P300 potentials.
Prevalence of delirium, depression, anxiety, and post-traumatic stress disorder among COVID-19 patients: protocol for a living systematic review
Authors: Shi Jiyuan , Gao Ya , Zhao Liang , Li Yuanyuan , Yan Meili , Mingming Niu , Chen Yamin , Song Ziwei , Zhang Ruixing , Zhang Lili , Tian Jinhui
Published: October 2020

Background Previous studies on the impact of corona virus disease 2019 (COVID-19) on the mental health of the patients has been limited by the lack of relevant data. With the rapid and sustained growth of the publications on COVID-19 research, we will perform a living systematic review (LSR) to provide comprehensive and continuously updated data to explore the prevalence of delirium, depression, anxiety, and post-traumatic stress disorder (PTSD) among COVID-19 patients.Methods We will perform a comprehensive search of the following databases: Cochrane Library, PubMed, Web of Science, Embase, and Chinese Biomedicine Literature to identify relevant studies. We will include peer-reviewed cross-sectional studies published in English and Chinese. Two reviewers will independently assess the methodological quality of included studies using the Joanna Briggs Institute Prevalence Critical Appraisal tool and perform data extraction. In the absence of clinical heterogeneity, the prevalence estimates with a 95% confidence interval (CI) of delirium, depression, anxiety, and post-traumatic stress disorder (PTSD) will be calculated by using random-effects model to minimize the effect of between-study heterogeneity separately. The literature searches will be updated every three months. We will perform meta-analysis if any new eligible studies or data are obtained. We will resubmit an updated review when there were relevant changes in the results, i.e. when outcomes became statistically significant (or not statistically significant anymore) or when heterogeneity became substantial (or not substantial anymore).Discussion This LSR will provide an in-depth and up-to-date summary of whether the common neuropsychiatric conditions observed in patients hospitalized for severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS) are also prevalent in a different stage of COVID-19 patients.Systematic review registrationPROSPERO CRD42020196610
FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway
Authors: Tuluhong Dilihumaer , Chen Tao , Wang Jingjie , Zeng Huijuan , Li Hanjun , Dunzhu Wangmu , Li Qiurong , Wang Shaohua
Published: October 2020

Background: Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our study was to detect the functions of FZD2 and explore its mechanism in BC.Methods: The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC) respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were conducted separately to test cell viability, invasion, migration, apoptosis and cell cycle distribution. Epithelial-mesenchymal transition (EMT) biomarkers were determined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo.Results: FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway.Conclusion: FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.
Is oxygen therapy beneficial for normoxemic patients with acute heart failure? A propensity score matched study
Authors: Yu Yue , Yao Ren-qi , Zhang Yu-feng , Wang Su-yu , Xi Wang , Wang Jun-nan , Huang Xiao-yi , Yao Yong-ming , Wang Zhinong
Published: October 2020

Background: The clinical efficiency of routine oxygen therapy is uncertain in patients with acute heart failure (AHF) who do not have hypoxemia. The aim of this study was to investigate the association between oxygen therapy and clinical outcomes in normoxemic patients hospitalized with AHF using real-world data.Methods: Normoxemic patients diagnosed with AHF on ICU admission from the electronic ICU (eICU) Collaborative Research Database were included in the current study, in which the study population was divided into the oxygen therapy group and the ambient-air group. Propensity score matching (PSM) was applied to create a balanced covariate distribution between patients receiving supplemental oxygen and those exposed to ambient air. Linear regression and logistic regression models were performed to assess the associations between oxygen therapy and length of stay (LOS), and all-cause in-hospital as well as ICU mortality rates, respectively. A series of sensitivity and subgroup analyses were conducted to further validate the robustness of our findings.Results: A total of 2,922 normoxemic patients with AHF were finally included in the analysis. Overall, 42.1% (1,230/2,922) patients were exposed to oxygen therapy, and 57.9% (1,692/2,922) patients did not receive oxygen therapy (defined as the ambient-air group). After PSM analysis, 1,122 pairs of patients were matched: each patient receiving oxygen therapy was matched with a patient without receiving supplemental oxygen. The multivariable logistic model showed that there was no significant interaction between the ambient air and oxygen group for all-cause in-hospital mortality (odds ratio [OR] 1.30; 95% confidence interval [CI] 0.92-1.82; P＝0.138) or ICU mortality (OR 1.39; 95% CI 0.83-2.32; P＝0.206) in the post-PSM cohorts. In addition, linear regression analysis revealed that oxygen therapy was associated with prolonged ICU LOS (OR 1.11; 95% CI 1.06-1.15; P＜0.001) and hospital LOS (OR 1.06; 95% CI 1.01-1.10; P＝0.009) after PSM. Furthermore, the absence of an effect of supplemental oxygen on mortality was consistent in all subgroups.Conclusions: Routine use of supplemental oxygen in AHF patients without hypoxemia was not found to reduce all-cause in-hospital mortality or ICU mortality.
Genomic Variations in SARS-CoV-2 Strains at the Target Sequences of Nucleic Acid Amplification Tests
Authors: Cao Canhui , Yu Ruidi , Zeng Shaoqing , Liu Dan , Gong Wenjian , Li Ruyuan , Wang Siyuan , Yuan Yuan , Chi Jianhua , Liu Jiahao , Yu Yang , Jiao Xiaofei , Cai Guangyao , Jin Ning , Ye Fei , Gao Qinglei
Published: October 2020

Background
Nucleic acid amplification is the main method used to detect infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the false-negative rate of nucleic acid tests cannot be ignored.
Methods
Herein, we demonstrated genomic variations at the target sequences for the tests and the geographical distribution of the variations across countries by analyzing the whole-genome sequencing data of SARS-CoV-2 strains from the 2019 Novel Coronavirus Resource (2019nCoVR) database.
Results
Among the 21 pairs of primer sequences in regions ORF1ab, S, E, and N, the total length of primer and probe target sequences was 938 bp, with 131(13.97%) variant loci in 2415 (38.96%) isolates. Primer targets in the N region contained the most variations that were distributed among the most isolates, and the E region contained the least. Single nucleotide polymorphisms were the most frequent variation, with C to T transitions being detected in the most variant loci. G to A transitions and G to C transversions were the most common and had the highest isolate density. Genomic variations at the three mutation sites N: 28881, N: 28882, and N: 28883 were the most commonly detected, including in 608 SARS-CoV-2 strains from 33 countries, especially in the United Kingdom, Portugal, and Belgium.
Conclusions
Our work comprehensively analyzed genomic variations on the target sequences of the nucleic acid amplification tests, offering evidence to optimize primer and probe target sequence selection, thereby improving the performance of the SARS-CoV-2 diagnostic test.
Enhanced cell survival and therapeutic benefits of IL-10-expressing multipotent mesenchymal stromal cells for muscular dystrophy
Authors: Kasahara Yuko Nitahara , Kuraoka Mutsuki , Oda Yuki , Kinoh Hiromi Hayashita , Takeda Shin’ichi , Okada Takashi
Published: October 2020

Background:Multipotent mesenchymal stromal cells (MSCs) are potentially therapeutic for muscle disease because they can accumulate at the sites of injury and are immunosuppressive. MSCs are attractive candidates for cell-based strategies that target diseases with chronic inflammation, such as Duchenne muscular disease (DMD). We focused on the IL-10 based anti-inflammatory properties and hypothesized that IL-10 could increase the typically low survival of MSCs by exerting a paracrine effect after transplantation.Methods:We developed a continuous IL-10 expression system of MSCs using an adeno-associated virus (AAV) vector. To investigate the potential benefits of AAV/IL-10 vector-transduced MSCs (IL-10-MSCs), we examined the cell survival rates in the skeletal muscles after intramuscular injection into mice and dogs. The systemic treatment of IL-10-MSCs derived from dental pulp (DPSCs) was comprehensively analyzed using the canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to DMD patients. Results:In vivo bioluminescence imaging analysis revealed higher retention of IL-10-MSCs injected into the hind-limb muscle of mice. In the muscles of dogs, myofiber-like tissue was formed after the stable engraftment of IL-10-MSCs. Repeated systemic administration of IL-10-DPSCs into CXMDJ model resulted in long-term engraftment of cells, slightly increased serum levels of IL-10. IL-10-hDPSCs showed remarkably reduced expression of pro-inflammatory MCP-1, and upregulated stromal-derived factor-1 (SDF-1). In fact, MRI and histopathology of the hDPSC-treated CXMDJ indicated the regulation of inflammation in the muscles, but not myogenic differentiation from treated cells. hDPSC-treated CXMDJ showed improved running capability, and recovery in tetanic force with concomitant increase in physical activity. Serum creatine kinase levels, which increased immediately after exercise, were suppressed in the IL-10-hDPSC-treated CXMDJ. Conclusions:In case of local injection, IL-10-MSCs could maintain the long-term engraftment status and facilitate associated tissue repair. In case of repeated systemic administration, IL-10-MSCs facilitated the long-term retention of the cells in the skeletal muscle and also protected muscles with physical damage-induced injury, which improved muscle dysfunction in DMD. We can conclude that the local and systemic administration of IL-10-producing MSCs offers potential benefits for DMD therapy, through the beneficial IL-10 paracrine effects involving SDF-1.