ABSTRACT
PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
Subject(s)
Humans , Cell Membrane , Mutation, Missense , Phosphates/metabolism , Sodium-Phosphate Cotransporter Proteins, Type III/geneticsABSTRACT
Objective: To explore the potential mechanism of acupuncture and moxibustion in treating Crohn disease (CD) by evaluating the changes in histamine and inflammatory factors in the skin tissue at Tianshu (ST25) of rats.Methods: Fifty-eight Sprague-Dawley rats were randomly divided into a normal group (n=14) and a CD-modeling group (n=44). Rats in the CD-modeling group received enema with 2,4,6-trinitrobenzene sulfonic acid plus ethanol to establish CD models. The enema was repeated once every 7 d for a total of 4 times. After modeling, four modeled rats and four normal rats were randomly selected for model identification. After the CD model was successfully established, the remaining rats in the CD-modeling group were randomly divided into a model group, an acupuncture group, a moxibustion group, and a Western medication group, with ten rats in each group. The rats in the acupuncture and moxibustion groups were treated with acupuncture or moxibustion at Tianshu (ST25) and Shangjuxu (ST37); the rats in the Western medication group were treated with mesalazine enteric-coated tablets by gavage for continuous 7 d. After the intervention, the colon tissue of rats in each group was collected. After gross observation, hematoxylin-eosin (HE) staining was performed to further observe the pathological changes. The expression of histamine in the skin tissue at Tianshu (ST25) was detected by enzyme-linked immunosorbent assay. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18, IL-10, and IL-6 in the skin tissue at Tianshu (ST25) was detected by Western blotting. Results: Compared with the normal group, the colonic wall of rats in the model group showed cobblestone-like changes, local ulcers, and polyps in dark red and thickening and hardening. HE staining showed local loss of mucosal epithelial layer and formation of slit-like ulcers, destruction of mucosal glands, edema, and infiltration of inflammatory cells in lamina propria and submucosa, and occasional formation of sarcoid-like granuloma. The levels of histamine and IL-6 were significantly up-regulated (P<0.01, P<0.05), and the levels of TNF-α, IL-18, and IL-10 were significantly down- regulated (P<0.01 or P<0.05) in the skin tissue at Tianshu (ST25) of rats in the model group. Compared with the model group, the pathomorphological damage of the colon tissue of rats in the acupuncture group, moxibustion group, and Western medication group was significantly improved. The levels of histamine and IL-6 were significantly down- regulated (P<0.01, P<0.05), and the level of IL-10 was significantly up-regulated (P<0.01) in the skin at Tianshu (ST25) of rats in the acupuncture group. The levels of histamine and IL-6 were significantly down-regulated (P<0.01, P<0.05), and the levels of TNF-α, IL-18, and IL-10 were significantly up-regulated (P<0.01 or P<0.05) in the skin tissue at Tianshu (ST25) of rats in the moxibustion group. The level of histamine was significantly down-regulated (P<0.01), and the levels of IL-18 and IL-10 were significantly up-regulated (P<0.05, P<0.01) in the skin tissue of rats in the Western medication group. Compared with the acupuncture group, the level of IL-10 in the skin tissue at Tianshu (ST25) of rats in the moxibustion group was significantly up-regulated (P<0.01). Conclusion: The inflammatory responses in the skin tissue at Tianshu (ST25) may be the external manifestation of CD. Significant differences in the regulation of inflammatory responses in the skin tissue at Tianshu (ST25) between acupuncture and moxibustion exist, which may be caused by the differences in the stimulation characteristics between acupuncture and moxibustion.
ABSTRACT
@#Objective To investigate the risk factors for fatigue impairment in patients with multiple system atrophy （MSA）. Methods A total of 101 patients with MSA were enrolled，and according to the score of Fatigue Severity Scale （FSS），they were divided into non-fatigue group （<4 points） with 41 patients and fatigue group （≥4 points） with 60 patients. A binary logistic regression analysis was used to screen for the risk factors for fatigue in patients with MSA. Results There were significant differences in sex，course of disease，clinical classification，urinary retention，UMSARS-I，UMSARS-II，UMSARS-I+II，UMSARS-IV，bradykinesia，myotonia，ataxia，abnormal gait and posture，and ESS score between the patients with different between fatigue levels （P<0.05）. The binary logistic regression analysis showed that UMSARS-I and ESS scores were independent risk factors for fatigue in MSA patients （P<0.05）. Conclusion Fatigue impairment in patients with MSA is caused by multiple factors，among which UMSARS-I and ESS scores are independent risk factors for fatigue in MSA.
ABSTRACT
Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC. In this review, considering mechanistic studies of these genes at the cellular level and in animals, we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients. Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics, provides a summary of the known composition of brain calcification, and identifies some potential therapeutic targets for PFBC.
Subject(s)
Animals , Brain Diseases/therapy , Xenotropic and Polytropic Retrovirus Receptor , Brain/pathologyABSTRACT
The incidence of emotion disability-related diseases in adolescents is increasing year by year, causing great harm to their physical and mental health, even affecting them until adulthood. However, the mechanism of this has not been fully clarified. The default mode network is a brain network composed of brain regions that are still active in the resting state. DMN is a hot pot in the field of resting state brain function research, but few studies have focused on its pathological changes in the adolescents with emotion disability-related diseases. In recent years, a number of articles related to adolescent emotion disorders have provided clues for understanding the characteristics and potential mechanisms of adolescent emotion disorders from the perspective of imaging. This paper summarized the related research over the years and found that the occurrence of emotion disorders is closely related to the activation of the default mode network brain regions, cortical thickness, gray matter volume or density, and changes in functional connections between brain areas.Some changes in brain structure and function can be used as predictive factors. In this paper, by summarizing the changes in brain imaging of these emotion disorders, we hope to explore new neuroimaging landmark changes, which can provide theoretical basis for the prevention, diagnosis and treatment of emotion disorders related diseases in adolescents.
ABSTRACT
Aim To observe the inhibitory effect of neferine(Nef)on the migration and invasion of non-small cell lung cancer(NSCLC)H1299 cells by blocking ROCK pathway.Methods H1299 cells were taken for in vitro culture, and treated with different concentrations of Nef.H1299 cell viability was measured by CCK-8 method to determine the dose of the experimental group.The migration and invasion abilities of H1299 cells were detected by cell scratch test and Transwell chamber test.The expression of matrix metalloproteinases MMP-2 and MMP-9 secreted from lung cancer cells was detected by enzyme linked immunosorbent assay(ELISA).The protein level of ROCK1 in H1299 cells was tested by real-time fluorescent quantitative PCR and Western blot; the binding mode and affinity between Nef and ROCK1 were stimulated by AutoDock semi flexible docking method.Results The doses of Nef in the experimental group were determined as 4, 6 and 10 μmol·L-1.These three concentrations of Nef could inhibit the migration and invasion of H1299 lung cancer cells to a certain degree in a dose-dependent manner.At the same time, Nef reduced the expression of MMP-2, MMP-9 and ROCK1 proteins related to the migration and invasion of the cancer cells.In addition, the affinity of Nef to ROCK1 was significantly higher than that of fasudil, an inhibitor of ROCK, and the binding force was stronger to A-chain of ROCK1.Conclusions As a potential natural anticancer compound, Nef can inhibit the migration and invasion of NSCLC by reducing the expression of MMP-2, MMP-9 and ROCK1 proteins related to the migration and invasion of the cancer cells.
ABSTRACT
[Abstract] Objective To investigate the effect of hippocampal brain derived neurotrophic factor precursor (proBDNF) in cognitive dysfuction induced by social isolation. Methods Thirty C57BL / 6 J male mice (4-week old) were randomly divided into group house (GH,n = 15) and socially isolated (SI,n = 15) groups. The GH group (5 mice / cage) and SI group (1 mice / cage) were reared separately under the same conditions. The novel object recognition test and the novel place recognition test were used to evaluate the cognitive function. The expression of BDNF mRNA in the hippocampus was detected by Real-time PCR. The expression of BDNF and proBDNF in hippocampus was detected by Western blotting. Matrix metallopeptidase-9 (MMP-9) and tissue plasminogen activator (tPA) were extracellular enzymes that catalyzed the transformation of proBDNF into mature BDNF. Expression of MMP-9 and tPA mRNA in the hippocampus were detected by Real-time PCR. Results Compared with the GH group, the SI group showed significantly reduced discrimination ratio in the novel object recognition test and novel place recognition test. The result of Real-time PCR showed that there was no difference in the expression of BDNF mRNA between SI group and GH group. The result of Western blotting showed that the expression level of proBDNF in the hippocampus of SI group increased significantly compared with the GH group (P<0. 01),and no difference in BDNF expression was found between the two groups; Compared with the GH group, the BDNF/ proBDNF ratio in the hippocampus of SI group decreased. In addition, the result of Real-time PCR showed that the expression level of MMP-9 and tPA mRNA in the hippocampus of SI group decreased significantly compared with the GH group. Conclusion The social isolation-induced cognitive dysfuction in mice may be related to the up-regulation of proBDNF in the hippocampus.
ABSTRACT
OBJECTIVE@#To observe the effect of moxibustion combined with @*METHODS@#A total of 240 close contacts of COVID-19 were randomized into an observation group (120 cases, 18 cases dropped off) and a control group (120 cases, 58 cases dropped off). Conventional observation was adopted in the control group. Moxibustion combined with Daiwenjiu plaster was given in the observation group, moxibustion was applied at Zusanli (ST 36), Hegu (LI 4) and Shenque (CV 8), 10 min each acupoint, once a day; @*RESULTS@#In the follow-up, SRQ-20 score was decreased compared before treatment (@*CONCLUSION@#Moxibustion combined with
Subject(s)
Humans , Acupuncture Points , COVID-19 , Mental Disorders , Moxibustion , SARS-CoV-2ABSTRACT
BACKGROUND@#Nucleolar protein 6 (NOL6) is a nucleolar RNA-associated protein that is highly conserved between species. It has been proved to be associated with the prognosis of liver cancer. However, the underlying mechanism has not been fully established. This study aimed to assess the relationship between NOL6 and liver cancer prognosis.@*METHODS@#We constructed an NOL6-short hairpin RNA (shRNA)-expressing lentivirus. Through viral transfection, cell growth assay and fluorescence-activated cell sorting, we evaluated the effect of shRNA-mediated NOL6 knockdown on the proliferation, colony formation, and apoptosis of hepatocellular carcinoma (HCC) cells. The relationship between NOL6 expression and HCC patient survival has been established through bioinformatics analysis. We also explored the downstream molecular regulatory network of NOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.@*RESULTS@#Increased NOL6 expression was detected in HCC cells compared to normal controls; HCC patients with high NOL6 expression had poorer prognoses than those with low expression. NOL6 knockdown inhibited HCC cell proliferation, apoptosis, and colony formation. Also, MAPK8, CEBPA, and FOSL1 were selected as potential downstream genes of NOL6.@*CONCLUSIONS@#NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes. Moreover, NOL6 is considered to be associated with poor prognosis in HCC patients.
Subject(s)
Humans , Apoptosis/genetics , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Nuclear Proteins , PrognosisABSTRACT
A common clinical problem encountered by colorectal surgeons is the secondary tumors of the ovary (STO), particularly in young female patients. Most STO are from the digestive tract, and the known possible metastatic mechanisms include lymphatic, hematogenous, and intraperitoneal spreading. The molecular and histopathological characteristics of STO from different sites are diverse. It is particularly important to correctly identify the origin and feature of STO, which should be clarified by combining medical history, histopathology, immunohistochemistry, molecular biology, imaging and other means. The prognosis of patients with STO is poor in general. Comprehensive therapies based on surgical resection can benefit some patients. There is no specific treatment for STO at present, but not giving up easily on these patients is the right choice that every surgeon should understand.
Subject(s)
Female , Humans , Colorectal Neoplasms/therapy , Krukenberg Tumor , Ovarian Neoplasms/surgery , Prognosis , SurgeonsABSTRACT
Primary and secondary airway problems directly affect mortality and disability in critically ill children in pediatric intensive care unit(PICU). Soft bronchoscope, as an important method for the diagnosis and interventional treatment of airway lesions in critically ill children in PICU, requires standardized seamless nursing cooperation throughout the whole process.This article discussed the nursing cooperation before, during and after soft bronchoscope operation in PICU.
ABSTRACT
Tracheobronchial foreign body aspirations may cause cardiopulmonary arrest and sudden death.The incidence in children is higher than in adults.Rapid diagnosis and treatment are live saving.In this paper, we aimed to present our experience in tracheal foreign body aspirations by fiberoptic bronchoscopy.
ABSTRACT
Children in the pediatric intensive care unit who continue to have ventilator-assisted breathing are often difficult to get off-line due to respiratory system disease, cardiovascular system disease, nervous system disease, nutritional status, genetic metabolism, abnormal diaphragm movement and other factors.Through the diagnosis and treatment of flexible bronchoscope, the etiology could be identified, the ventilation function is effectively improved, and the cure rate of weaning difficulty increases.This paper discussed the etiological diagnosis and treatment of flexible bronchoscopy in children with difficulty in weaning from pediatric intensive care unit.
ABSTRACT
Objective:To investigate the characteristics of sublingual microcirculation in children with sepsis, and to explore the clinical value of sublingual microcirculation in the early diagnosis, therapeutic effect evaluation of sepsis in children.Methods:Children with sepsis and community acquired pneumonia(CAP) admitted in our hospital from December 2018 to December 2019 were included in the study, which was divided into sepsis group and control group(CAP group). In the sepsis group, large circulation indexes and sublingual microcirculation indexes were collected at 0, 6, and 24 hours after admission.Sublingual microcirculation indexes were collected by bypass dark field imaging.In the control group, large circulation indexes were collected after admission, and sublingual microcirculation indexes were collected during tracheal endoscopic examination after sedation.De Backer score(DBs), hetergeneity index(HI), hetergeneity index small(HIs), proportion of pefusedvessels(PPV), proportion of pefused small vessels(PPVs), total of vessel density(TVD), pefused vessel density(PVD), pefused small vessel density(PVDs)were selected as the evaluation index of sublingual microcirculation.The changes of macrocirculation and microcirculation indexes in the two groups were compared, and the correlation between age and microcirculation indexes in the control group was analyzed.Results:A total of 71 children, including 10 sepsis cases and 61 CAP cases, were collected.Among the 61 children with CAP, 9 children (2-48 months) in the same age range as the sepsis group were divided into control group A, and the indicators between the two groups were analyzed.Compared with control group A, PPV and PPVs were lower and DBs, HI, HIs, TVD were higher in the sepsis group at 0 hours( P<0.05). At 6 hours, HI in the sepsis group was still higher than that in control group A, and PPV, PPVs were higher than those at 0 hours.However, at 6 hours, PPVs was still lower than that of control group A( P<0.05), and HI, HIs did not improve compared with those at 0 hours( P>0.05). At 24 hours, HI, PPV and PPVs improved, no difference was found compared with the control group A( P<0.05), while HIs did not improve significantly( P>0.05). The age of the control group had a moderate negative correlation with HI, and a weak negative correlation with HIs( r=-0.420, P=0.001; r=-0.387, P=0.002). Conclusion:HI, HIs, PPV and PPVs are sensitive indexes of microcirculation disorder in children with sepsis.Fluid resuscitation therapy can improve the indexes of sublingual microcirculation in children with sepsis, but the improvement of sublingual microcirculation in children with sepsis is later than the recovery of macro circulation.HI and HIs are negatively correlated with month age in children with CAP.
ABSTRACT
Tracheobronchial foreign body aspirations may cause cardiopulmonary arrest and sudden death.The incidence in children is higher than in adults.Rapid diagnosis and treatment are live saving.In this paper, we aimed to present our experience in tracheal foreign body aspirations by fiberoptic bronchoscopy.
ABSTRACT
Children in the pediatric intensive care unit who continue to have ventilator-assisted breathing are often difficult to get off-line due to respiratory system disease, cardiovascular system disease, nervous system disease, nutritional status, genetic metabolism, abnormal diaphragm movement and other factors.Through the diagnosis and treatment of flexible bronchoscope, the etiology could be identified, the ventilation function is effectively improved, and the cure rate of weaning difficulty increases.This paper discussed the etiological diagnosis and treatment of flexible bronchoscopy in children with difficulty in weaning from pediatric intensive care unit.
ABSTRACT
Primary and secondary airway problems directly affect mortality and disability in critically ill children in pediatric intensive care unit(PICU). Soft bronchoscope, as an important method for the diagnosis and interventional treatment of airway lesions in critically ill children in PICU, requires standardized seamless nursing cooperation throughout the whole process.This article discussed the nursing cooperation before, during and after soft bronchoscope operation in PICU.
ABSTRACT
During the renal replacement therapy,the blood coagulation system is activated in the extracorporeal circulation line and the filter,resulting in blood coagulation. This can interrupt treatment and shorten the life of the ex﹣tracorporeal circulation line and filter. The consequences are the effectiveness of renal replacement therapy decrease While increasing Workload and treatment costs. Therefore,appropriate anticoagulation measures are needed to complete this treatment. To ensure the continuity of extracorporeal bypass,but also to monitor,detect and intervene for the compli﹣cations caused by anticoagulation. NoW,the general theory of renal replacement therapy and anticoagulation technology is discussed.
ABSTRACT
Ocular myasthenia gravis(OMG)is an autoimmune disease caused by neuromuscular junction transmission disorders and manifested mainly as fluctuating blepharoptosis and diplopia,with the extraocular muscles as the main involveed sites.While the pathogenesis of OMG remains unclear,some antibodies,complements,and cytokines may be the contributing factors.The diagnosis and treatment of OMG have been defined in recent years.This article reviews the pathogenesis,diagnosis,and treatment of OMG.
Subject(s)
Humans , Antibodies , Complement System Proteins , Cytokines , Myasthenia Gravis , Diagnosis , Pathology , Therapeutics , Oculomotor Muscles , PathologyABSTRACT
Retinopathy of prematurity(ROP)is a pathological neovascularization with fibrotic changes in the fundus of premature infants.It is a major cause of preventable blindness in children in both developing and developed countries.Treatment of ROP has long been a hot research topic in ophthalmology and pediatrics.With a clearer knowledge of the pathogenesis of ROP,more basic and clinical studies have been carried out.The anti-vascular endothelial growth factor therapy and surgical treatment have become mature strategies,and a variety of therapeutic drugs including insulin-like growth factor-1,transforming growth factor-β,polyunsaturated fatty acids,and β-adrenergic receptor blockers have been developed.This article reviews the recent advances in ROP.