Investigation of adverse reactions in healthcare personnel working in Level 3 barrier protection PPE to treat COVID-19.

PURPOSE OF THE STUDY: The aim of our study was to investigate potential adverse reactions in healthcare professionals working in Level 3 barrier protection personal protective equipment (L3PPE) to treat patients with COVID-19. STUDY DESIGN: By using a convenience sampling approach, 129 out of 205 randomly selected healthcare professionals from the First Affiliated Hospital of Zhejiang University School of Medicine were invited to take part in a WeChat messaging app survey, Questionnaire Star, via a survey link. Healthcare personnel details were collected, including profession, years of professional experience and adverse reactions while wearing L3PPE. Survey results were divided by profession and years of professional experience; differences in adverse reactions were compared. RESULTS: Among the 129 healthcare professionals surveyed, 21 (16.28%) were doctors and 108 (83.72%) were nurses. A total of 122 (94.57%) healthcare professionals experienced discomfort while wearing L3PPE to treat patients with COVID-19. The main reasons for adverse reactions and discomfort include varying degrees of adverse skin reactions, respiratory difficulties, heat stress, dizziness and nausea. Doctors had a lower incidence of rashes (χ2=4.519, p=0.034) and dizziness (χ2=4.123, p=0.042) when compared with nurses. Junior (8.5 years of experience or fewer) healthcare personnel also experienced a higher rate of heat stress when compared with senior personnel (more than 8.5 years greater) (χ2=5.228, p=0.022). CONCLUSION: More attention should be offered to healthcare personnel wearing L3PPE to treat patients with COVID-19 because they are susceptible to developing adverse reactions.

All-trans retinoic acid upregulates the expression of ciliary neurotrophic factor in retinal pigment epithelial cells.

Retinopathy of prematurity, a leading cause of visual impairment in low birth-weight infants, remains a crucial therapeutic challenge. Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor that promotes rod and cone photoreceptor survival and cone outer segment regeneration in the degenerating retina. Ciliary neurotrophic factor expression is regulated by many factors such as all-trans retinoic acid (ATRA). In this study, we found that ATRA increased CNTF expression in mouse retinal pigment epithelial (RPE) cells in a dose- and time-dependent manner, and PKA signaling pathway is necessary for ATRA-induced CNTF upregulation. Furthermore, we showed that ATRA promoted CNTF expression through CREB binding to its promoter region. In addition, CNTF levels were decreased in serum of retinopathy of prematurity children and in retinal tissue of oxygen-induced retinopathy mice. In mouse RPE cells cultured with high oxygen, CNTF expression and secretion were decreased, but could be recovered after treatment with ATRA. In conclusion, our data suggest that ATRA administration upregulates CNTF expression in RPE cells.

Analysis of factors related to radiation-induced oral mucositis in patients with head and neck tumors undergoing radiotherapy.

OBJECTIVE: To explore the risk factors of radiation-induced oral mucositis (RIOM) in patients with head and neck tumors undergoing radiotherapy. METHODS: A retrospective collection was conducted on patients with head and neck tumors who underwent radiotherapy and chemotherapy in our hospital from April 1, 2015 to April 1, 2019. They were divided into an incidence group (n = 48) and a non-incidence group (n = 76) based on whether RIOM occurred, and relevant data was collected for comparison. RESULTS: There were statistically significant differences between the two groups of patients in terms of tumor type, smoking percentage, education level percentage, tumor stage, oral mucosal inflammation stage, radiotherapy dose, mucosal protectants, and oral hygiene condition(P < 0.05); The regression analysis results showed that smoking (OR=1.274, 95 % CI: 1.095-2.007), high-dose radiotherapy (OR=1.223, 95 % CI: 1.098-2.077), and poor oral hygiene (OR=1.367, 95 % CI: 1.024-2.890) were risk factors for RIOM. CONCLUSION: Smoking, high-dose radiotherapy, and poor oral hygiene were risk factors for RIOM in head and neck patients after radiotherapy and chemotherapy.

Type III NRG-1 plays a regulatory role in the regeneration process of nerves from the beginning of transplantation.

The present study investigated the effect of type III Neuregulin-1 (NRG-1) on changes in the myelin sheath and the recovery of nerve function during the regeneration process following autologous nerve transplantation. Seventy-two Sprague-Dawley rats were divided into a Blank, Model and (antisense oligonucleotide, ASON) group. The Model and ASON groups of SD rats were subjected to autologous nerve transplantation, and the Blank group only had the sciatic nerve exposed. The Model and ASON groups were given local injections of 2 ml PBS buffer solution and 2 ml ASON of Type III NRG-1, respectively, the NRG-1 type III was inhibited by ASON. Changes in the sciatic nerve functional index (SFI) and conduction velocities were observed at different 6 time points. Regeneration of the myelin sheath was observed using transmission electron microscopy. Type III NRG-1 protein was detected using Western blotting and immunohistochemistry, and NRG-1 mRNA was detected using PCR. The SFI of the ASON group was lower than the Model group after transplantation. The conduction velocities of the ASON group on the 14th and 21st days after autologous nerve transplantation were lower than the Model group (P < 0.01). The protein and mRNA expression of type III NRG-1 in the ASON group was lower than the Model group at all 6 time points. The area of medullated nerve fibres was significantly different between the ASON group and the Model group on the 3rd day (P < 0.05), as was the number of medullated nerve fibres per unit area (P < 0.01). The diameter of axons was obviously different between the two groups (P < 0.01). Type III NRG-1 played an important regulatory role in the regeneration process of the nerve from the beginning of transplantation to the 28th day.

Changes in Type II NRG-1 Expression during Regeneration Following Autologous Nerve Transplantation in Rats.

AIM: To investigate the changes in type II neuregulin-1 (NRG-1) during the regeneration process following autologous sciatic nerve transplantation in rats. MATERIAL AND METHODS: In total, 40 healthy male Sprague-Dawley (SD) rats of clean grade with body weights between 250 g and 300 g were randomly divided into an experimental and control group, with 20 rats per group. Five time points were set, including the 3 < sup > rd < /sup > , 7 < sup > th < /sup > , 14 < sup > th < /sup > , 21 < sup > st < /sup > and 28 < sup > th < /sup > days after surgery. In the experimental group, reversed autologous transplantation of the sciatic nerve was performed, while in the control group, the sciatic nerve was simply exposed without autologous transplantation. At the different time points, changes in the rat footprints were observed, the sciatic functional index (SFI) was calculated, changes in the regeneration of the myelin sheath at the nerve end after transplantation were observed by transmission electron microscopy, changes in type II NRG-1 protein expression were detected by a western blot analysis, and changes in type II NRG-1 mRNA expression were detected by real-time PCR. RESULTS: The SFI in the experimental group was lower than that in the control group at all time points after surgery, and the SFI in the experimental group gradually increased; these differences were statistically significant (p < 0.05). The expression of type II NRG-1 protein in the experimental group was significantly increased on the 3rd day after nerve transplantation and peaked on the 7 < sup > th < /sup > day, which continued until the 28 < sup > th < /sup > day after surgery, indicating a significant difference from the control group (p < 0.01). NRG-1 mRNA expression was markedly increased on the 7th day after nerve transplantation, further increased, and peaked on the 14 < sup > th < /sup > day (p < 0.01). The area of medullated nerve fibers (?m2) in the experimental group significantly differed from that in the control group on the 7 < sup > th < /sup > , 14 < sup > th < /sup > , 21 < sup > st < /sup > and 28 < sup > th < /sup > days (p < 0.01), and the diameters of the axons in the experimental group notably differed from those in the control group on the 7 < sup > th < /sup > , 14 < sup > th < /sup > and 21 < sup > st < /sup > days (p < 0.01). CONCLUSION: Type II NRG-1 expression peaked between the 3 < sup > rd < /sup > day and 14 < sup > th < /sup > day after autologous nerve transplantation and is likely involved in the regulation of myelin sheath regeneration during this period.

Comparison of ligase detection reaction and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B.

AIM: To compare the ligase detection reaction (LDR) and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B infection. METHODS: Mixtures of plasmids and serum samples from 52 chronic hepatitis B patients with low abundant lamivudine-resistant mutations were tested with LDR and real-time PCR. Time required and reagent cost for both assays were evaluated. RESULTS: Real-time PCR detected 100, 50, 10, 1 and 0.1% of YIDD plasmid, whereas LDR detected 100, 50, 10, 1, 0.1, and 0.01% of YIDD plasmid, in mixtures with YMDD plasmid of 10(6) copies/mL. Among the 52 clinical serum samples, completely concordant results were obtained for all samples by both assays, and 39 YIDD, 9 YVDD, and 4 YIDD/YVDD were detected. Cost and time required for LDR and real-time PCR are 60/80 CNY (8/10.7 US dollars) and 4.5/2.5 h, respectively. CONCLUSION: LDR and real-time PCR are both sensitive and inexpensive methods for monitoring low abundant YMDD mutants during lamivudine therapy in patients with chronic hepatitis B. LDR is more sensitive and less expensive, while real-time PCR is more rapid.

Mechanisms and roles by which IRF-3 mediates the regulation of ORMDL3 transcription in respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infancy, which is a major risk factor for recurrent wheezing and asthma. Orosomucoid 1-like protein 3 (ORMDL3) has been reported to associate with virus-triggered recurrent wheezing and asthma in children. However, little is known about how ORMDL3 is involved into RSV infection. In this study, we showed that the mRNA expression of ORMDL3 is significantly increased in the peripheral blood lymphocytes of infants with RSV-induced bronchiolitis compared with uninfected controls, also increased in bronchial epithelial cells and lung fibroblasts following RSV infection in vitro. To investigate the underlying mechanisms of RSV-induced ORMDL3 expression, we performed in silico analysis of the binding sites of several transcription factors in the ORMDL3 promoter. The proximal interferon-regulatory factor-3 (IRF-3) binding site positively regulated ORMDL3 transcription following exposure to RSV, as determined through mutational analysis. Overexpression and RNA interference experiments targeting IRF-3 showed that it regulates the expression of ORMDL3 following RSV exposure. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay showed that IRF-3 binds directly to the promoter of the ORMDL3 gene. Furthermore, we confirmed that expression of IRF-3 is significantly increased and shows a strong linear correlation with increased ORMDL3 in the peripheral blood lymphocytes from infants with RSV-induced bronchiolitis. Our results indicate that IRF-3 is an important regulator of ORMDL3 induction following RSV infection by binding directly to the promoter of ORMDL3, which may be implicated in the inflammatory and immune reactions involved in bronchiolitis and wheezing diseases.

Effects of comprehensive intensive therapies on the change of intima-media thickness of carotid arteries in type 2 diabetic patients: A report of 4-year follow-up with a literature review.

BACKGROUND: The aim was to evaluate the effect of comprehensive intensive therapy on the carotid and femoral arteries of intima-media thickness in patients with type 2 diabetes mellitus after 4-year follow-up. METHODS: In this prospective 4-year study, patients (N = 210) with newly diagnosed type 2 diabetes received either comprehensive intensive therapy (n = 110) or conventional therapy (n = 100). Blood pressure, blood glucose and lipid levels were monitored every 3-6 months, and carotid and femoral arteries of intima-media thickness were monitored with ultrasonography. For the literature review, various databases were searched until 20 December 2014 for studies that evaluated effects of intensive multi-factorial therapies on comprehensive intensive therapy in type 2 diabetes mellitus patients. RESULTS: The comprehensive intensive therapy group had a smaller rate of carotid intima-media thickness increase than the conventional therapy (control) group (p < 0.05). The carotid intima-media thickness in comprehensive intensive therapy group remained stable while the adjusted rate of carotid intima-media thickness increase was 12.55% in the control group. The femoral intima-media thickness change was also smaller in comprehensive intensive therapy group but the difference over time did not reach significance. CONCLUSION: The carotid intima-media thickness remained stable in type 2 diabetes mellitus patients who received comprehensive intensive therapy, suggesting that multi-factorial intensive therapies might have potential in reducing macro-vascular events in these patients.

Expression of interferon regulatory factor 5 is regulated by the Sp1 transcription factor.

The transcription factor, interferon regulatory factor 5 (IRF5), is important in the induction of type I interferon, proinflammatory cytokines and chemokines, and is involved in autoimmune diseases and tumourigenesis. However, the mechanisms underlying the transcriptional regulation of wild­type IRF5 remain to be fully elucidated. The present study was primarily designed to clarify whether specificity protein 1 (Sp1) was involved in the regulation of IRF5. Initially, the IRF5 promoter region was cloned and its promoter activity was examined using Hela and HEK 293 cells. Deletion analyses revealed that the region spanning ­179 to +62 was the minimal promoter of IRF5. Bioinformatics analyses showed that this region contained three putative Sp1 binding sites, and mutational analyses revealed that all the Sp1 sites contributed to transcriptional activity. Secondly, the overexpression of Sp1 was found to increase the activity of the IRF5 promoter and the mRNA level of IRF5, determined using reporter gene assays and polymerase chain reaction analysis, respectively. By contrast, treatment with mithramycin and Sp1 small interfering RNA significantly reduced the activity of the IRF5 promoter and the mRNA level of IRF5. Finally, the results of an electrophoretic mobility shift assay and a chromatin immunoprecipitation assay demonstrated that Sp1 bound to the promoter region of IRF5 in vitro and in vivo. These results suggested that the Sp1 transcription factor is the primary determinant for activating the basal transcription of the IRF5.

Analysis of differentially expressed genes based on microarray data of glioma.

Glioma represents one of the main causes of cancer-related death worldwide. Unfortunately, its exact molecular mechanisms remain poorly understood, which limits the prognosis and therapy. This study aimed to identify the critical genes, transcription factors and the possible biochemical pathways that may affect glioma progression at transcription level. After downloading micro-array data from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between glioma and normal samples were screened. We predicted novel glioma-related genes and carried on online software DAVID to conduct GO enrichment and transcription factor analysis of these selected genes. String software was applied to construct a PPI protein interaction network, as well as to find the key genes and transcription factors in the regulation of glioma. A total of 97 DEGs were identified associated with cancer, the GO enrichment analysis indicated these DEGs were mainly relevant to immune responses as well as regulation of cell growth. In addition, the transcription factor analysis showed these DEGs were regulated by the binding sites of transcription factors GLI2, SP1, SMAD7, SMAD3, RELA, STAT5B, CTNNB1, STAT5A, TFAP2A and SP3. PPI protein interaction network analysis demonstrated the hub nodes in the interaction network were EGFR, TGFB1, FN1 and MYC. The hub DEGs may be the most critical in glioma and could be considered as drug targets for glioma therapy after further exploration. Besides, with the identification of regulating transcription factors, the pathogenesis of glioma at transcription level might be brought to light.

E3 ubiquitin ligase Cbl-b suppresses human ORMDL3 expression through STAT6 mediation.

Orosomucoid 1-Like Protein 3 (ORMDL3) is an asthma candidate gene and Casitas B lineage lymphoma b (Cbl-b), an E3 ubiquitin ligase, is a critical factor in maintaining airway immune tolerance. However, the association of Cbl-b with ORMDL3 for asthma is unclear. Here, we show that expression of ORMDL3 is significantly increased and shows a strong linear correlation with decreased Cbl-b in the peripheral blood of recurrent wheeze patients. To elucidate the molecular mechanisms underlying this correlation, we identified that Cbl-b suppressed the transcriptional activity and mRNA expression of ORMDL3 in vivo. Further investigation showed that phosphorylation of signal transducer and activator of transcription 6 (STAT6) was induced by interleukin 4 bound to the ORMDL3 promoter, while Cbl-b reduced the phosphorylation of STAT6. Our results show that Cbl-b suppresses human ORMDL3 expression through STAT6.

Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis.

Epilepsy is characterized by the occurrence of repetitive seizures and can greatly affect a patient's cognition, particularly in terms of learning and memory. Orexin-A is an excitatory neuropeptide produced by the lateral hypothalamus that has been shown to be involved in learning and memory. A reduction in the levels of orexin-A after seizures may underlie the learning and memory impairments induced by epilepsy. Thus, we used pentylenetetrazol (PTZ)-kindled rats to investigate the effects of orexin-A on learning and memory and the involvement of neurogenesis in the dentate gyrus in OX1R-mediated ERK1/2 activation. A Morris water maze test revealed reduced escape latencies, prolonged times in the target quadrant and an increased number of platform crossings in PTZ-kindled rats exposed to orexin-A. These ameliorating effects of orexin-A on spatial learning and memory were attenuated by the intracerebroventricular injection of the OX1R antagonist SB334867 or the ERK1/2 inhibitor U0126. Further studies using bromodeoxyuridine (BrdU) revealed that orexin-A increased the number of BrdU-positive cells, doublecortin (DCX)/BrdU levels and the number of NeuN/BrdU double-positive nuclei in the dentate gyrus of PTZ-kindled rats. However, these effects were inhibited by treatment with SB334867 or U0126. Taken together, these data suggest that orexin-A attenuated the impairment of spatial learning and memory in PTZ-kindled rats and that this attenuation involved neurogenesis in the dentate gyrus via OX1R-mediated ERK1/2 activation.

Control of hypertension in rats using volatile components of leaves of Taxus chinensis var. mairei.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Taxus chinensis var. mairei (Taxaceae) is used traditionally to fill pillows in some rural areas of China. Its volatile substances have been speculated to be capable of improving sleep quality, making blood pressure stable, and having diuretic capacity as recorded in Ancient Chinese Materia Medica. Using animal models and new technologies, we confirmed the hypotensive potential of volatile components from leaves of Taxus chinensis var. mairei (VCLT). MATERIALS AND METHODS: VCLT was obtained by supercritical CO(2) extraction equipment from Taxus chinensis var. mairei fresh leaves. Hypertensive rats were pre-induced by intraperitoneal (i,p.) injection of Nω-Nitro-l-Ariginine (l-NNA) for 15 days (15mg/kg, twice a day), then divided into 5 groups and subjected to the following treatments. l-NNA group (group 1) receiving l-NNA alone (15mg/kg, i.p., twice per day for 6 weeks); in addition to receiving l-NNA same as group 1, Hydrochlorothiazide (HDZ) group (group 2) receiving HDZ (orally administration, 5mg/kg, once per day for 6 weeks); VCLT groups (groups 3-5), including VCLT1, VCLT2, VCLT3. The VCLT rats were housed in an enclosed cage (2 rats/0.064m(3)). VCLT was mixed well and sprayed on fresh leaves surface of Taxus chinensis var. mairei (100ml/kg) with three dosages: 167g/kg (VCLT1), 233g/kg (VCLT2) and 333g/kg (VCLT3), respectively. Systolic Blood Pressure (SBP), plasma nitric oxide (NO), plasma angiotensin II, postprandial blood glucose, fasting blood glucose and blood lipids were determined. RESULTS: VCLT prevented the increase of SBP and plasma angiotensin II in l-NNA treated rats. Although VCLT does not significantly reduce blood triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), it decreases total cholesterol (TC) while increasing plasma NO levels in a dose-dependent manner. CONCLUSION: VCLT can be used as a natural and supplementary reagents for the treatment of hypertension.