C-X-C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through ß-catenin-inhibited fatty acid oxidation.

The prevalence of chronic kidney disease (CKD) is highly increasing. Renal fibrosis is a common pathological feature in various CKD. Previous studies showed tubular cell senescence is highly involved in the pathogenesis of renal fibrosis. However, the inducers of tubular senescence and the underlying mechanisms have not been fully investigated. C-X-C motif chemokine receptor 4 (CXCR4), a G-protein-coupled seven-span transmembrane receptor, increases renal fibrosis and plays an important role in tubular cell injury. Whereas, whether CXCR4 could induce tubular cell senescence and the detailed mechanisms have not studied yet. In this study, we adopted adriamycin nephropathy and 5/6 nephrectomy models, and cultured tubular cell line. Overexpression or knockdown of CXCR4 was obtained by injection of related plasmids. We identified CXCR4 increased in injury tubular cells. CXCR4 was expressed predominantly in renal tubular epithelial cells and co-localized with adipose differentiation-related protein (ADRP) as well as the senescence-related protein P16INK4A . Furthermore, we found overexpression of CXCR4 greatly induced the activation of ß-catenin, while knockdown of CXCR4 inhibited it. We also found that CXCR4 inhibited fatty acid oxidation and triggered lipid deposition in tubular cells. To inhibit ß-catenin by ICG-001, an inhibitor of ß-catenin, could significantly block CXCR4-suppressed fatty acid oxidation. Taken together, our results indicate that CXCR4 is a key mediator in tubular cell senescence and renal fibrosis. CXCR4 promotes tubular cell senescence and renal fibrosis by inducing ß-catenin and inhibiting fatty acid metabolism. Our findings provide a new theory for tubular cell injury in renal fibrosis.

The CXCR4-AT1 axis plays a vital role in glomerular injury via mediating the crosstalk between podocyte and mesangial cell.

Glomeruli stand at the center of nephrons to accomplish filtration and albumin interception. Podocytes and mesangial cells are the major constituents in the glomeruli. However, their interdependency in glomerular injury has rarely been reported. Herein, we investigated the role of C-X-C chemokine receptor type 4 (CXCR4) in mediating the crosstalk between podocytes and mesangial cells. We found CXCR4 and angiotensin II (AngII) increased primarily in injured podocytes. However, type-1 receptor of angiotensin II (AT1) and stromal cell-derived factor 1α (SDF-1α), a ligand of CXCR4, were evidently upregulated in mesangial cells following the progression of podocyte injury. Ectopic expression of CXCR4 in 5/6 nephrectomy mice increased the decline of renal function and glomerular injury, accelerated podocyte injury and mesangial cell activation, and initiated CXCR4-AT1 axis signals. Additionally, treatment with losartan, an AT1 blocker, interrupted the cycle of podocyte injury and mesangial matrix deposition triggered by CXCR4. Podocyte-specific ablation of CXCR4 gene blocked podocyte injury and mesangial cell activation. In vitro, CXCR4 overexpression induced oxidative stress and renin angiotensin system (RAS) activation in podocytes, and triggered the communication between podocytes and mesangial cells. In cultured mesangial cells, AngII treatment induced the expression of SDF-1α, which was secreted into the supernatant to further promote oxidative stress and cell injury in podocytes. Collectively, these results demonstrate that the CXCR4-AT1 axis plays a vital role in glomerular injury via mediating pathologic crosstalk between podocytes and mesangial cells. Our findings uncover a novel pathogenic mechanism by which the CXCR4-AT1 axis promotes glomerular injury.

[Glycosylphosphatidylinositol biosynthesis deficiency 15 caused by GPAA1 gene mutation: a rare disease study]. / ç½•è§ç— ç ”ç©¶ï¼šGPAA1åŸºå› çªå˜å¯¼è‡´ç³–åŸºç£·è„‚é °è‚Œé†‡ç”Ÿç‰©åˆæˆç¼ºé™·15型.

A boy, aged 6 years, attended the hospital due to global developmental delay for 6 years and recurrent fever and convulsions for 5 years. The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year, with intermittent canker sores and purulent tonsillitis. During the fever period, blood tests showed elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, which returned to normal after the fever subsides. Electroencephalography showed epilepsy, and genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. The patient did not respond well to antiepileptic treatment, but showed successful fever control with glucocorticoid therapy. This article reports the first case of GPIBD15 caused by GPAA1 gene mutation in China and summarizes the genetic features, clinical features, diagnosis, and treatment of this disease, which provides a reference for the early diagnosis and treatment of GPIBD15.

Constructing a Highly Robust Interface Film for Enhancing Rate Performance of Graphite Anode via a Novel Electrolyte Additive.

Solid electrolyte interphase (SEI) is regarded as a key factor to enable high power outputs of Lithium-ion batteries (LIBs). Herein, we demonstrate a modified electrolyte consisting of a novel electrolyte additive, 1H,1H,2H,2H-perfluorooctyltrimethoxysilane (FTMS) to construct a highly robust and stable SEI on a graphite anode for LIBs to enhance its rate performance. With 2% FTMS, the anode presents an improved capacity retention from 77.6 to 91.2% at 0.5 C after 100 cycles and an improved capacity from 86 to 229 mAh g-1 at 2 C. Experimental characterizations and theoretical calculations reveal that FTMS is preferentially absorbed and reduced on graphite to construct an interface chemistry with uniform fluoride-containing organic lithium salt and silicon-containing polymer, which exhibits high flexibility and conductivity and endows the SEI with high robustness and stability. This work provides an effective way to address the issue of slow lithium insertion/desertion kinetics of graphite anodes.

Primary nephrotic syndrome relapse within 1 year after glucocorticoid therapy in children is associated with gut microbiota composition at syndrome onset.

BACKGROUND: Children with primary nephrotic syndrome (PNS) who relapse after glucocorticoid therapy are shown to have a decreased total proportion of butyrate-producing bacteria in the gut at onset. Glucocorticoid treatment changes the gut microbiota composition. It is unclear whether gut microbiota at remission right after therapy and gut bacteria other than butyrate-producing bacteria are associated with PNS relapse. METHODS: PNS relapse of paediatric patients within 1 year after glucocorticoid therapy was recorded. The gut microbiota composition, profiled with 16S rRNA gene V3-V4 region sequencing, was compared between relapsing and non-relapsing PNS children at onset before glucocorticoid treatment (preT group) and in PNS children at remission right after treatment (postT group), respectively. RESULTS: The gut microbiota composition of postT children significantly differed from that of preT children by having lower levels of Bacteroides, Lachnoclostridium, Flavonifractor, Ruminococcaceae UBA1819, Oscillibacter, Hungatella and Coprobacillus and higher levels of Ruminococcaceae UCG-013 and Clostridium sensu stricto 1 group. In the preT group, compared with non-relapsing patients, relapsing patients showed decreased Blautia, Dialister and total proportion of butyrate-producing bacteria and increased Oscillibacter, Anaerotruncus and Ruminococcaceae UBA1819. However, relapsing and non-relapsing postT children showed no difference in gut microbiota composition. CONCLUSIONS: PNS relapse-associated gut microbiota dysbiosis at onset, which includes alterations of both butyrate-producing and non-butyrate-producing bacteria, disappeared right after glucocorticoid therapy. It is necessary to study the association of the longitudinal changes in the complete profiles of gut microbiota after glucocorticoid treatment with later PNS relapse.

Identifying the Distinct Profiles of Transition Readiness in Chinese Pediatric Cancer Survivors.

BACKGROUND: Transition readiness is important for pediatric cancer survivors who need to move from pediatric to adult medical care. However, their transition readiness profiles merit further exploration. OBJECTIVES: The aim of this study was to use a person-centered approach to identify transition readiness profiles of Chinese pediatric cancer survivors aged 12 to 18 years, diagnosed at least 6 months before the study. METHODS: Transition readiness was assessed using the Chinese TRANSITION-Q Scale, and latent class analysis was performed to identify the transition readiness profiles as well as demographic and clinical factors associated with profile classification and to examine how self-efficacy and quality of life may differ between these profiles. RESULTS: A total of 139 pediatric cancer survivors were included. Three different transition readiness profiles were identified: high transition readiness, medium transition readiness, and low transition readiness. Age, treatment status, and parental working status were significantly associated with the transition readiness profile classifications. Those who were in the low transition readiness profile were likely to have lower self-efficacy and mobility scores than those in the high or medium transition readiness profiles. CONCLUSIONS: Three distinct transition readiness profiles existed in a sample of Chinese pediatric cancer survivors, indicating significant heterogeneity in their transition readiness. IMPLICATIONS FOR PRACTICE: Knowledge of transition readiness profiles can assist clinicians in screening pediatric cancer survivors for their profile memberships and provide targeted interventions for those with a low transition profile.

Analysis of the Correlation between the Level of Posttraumatic Growth and Social Support among Caregivers of Children with Acute Leukemia.

We investigate the current situation of stress burden and quality of life of primary caregivers of children with leukemia and analyze the correlation between their stress burden and quality of life, using the phenomenological research method in qualitative research. The posttraumatic growth experiences of the parents of children with leukemia included life perceptions (appreciation of life, change in priority of important things in life, and adjustment of self to reality); personal empowerment (increased sense of self-reliance and increased sense of self-achievement); and improvement of interpersonal relationships (increased family harmony, valuing parent-child bonding, benefiting from professional support from other parents and medical staff, and increased sense of empathy and altruism). The posttraumatic growth experiences of parents of children with leukemia are based on their roles (parenting) and responsibilities and can be used as an important basis for future trauma interventions, as well as an entry point for exploring the posttraumatic growth potential of parents of children with leukemia and ultimately improving the posttraumatic growth of parents of children with leukemia.

The Role of Nurses in Taking Care of Children With Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disease leading to an insulin deficiency that causes hyperglycemia and associated symptoms. It is considered the most common type of diabetes, with the 4Ts (going to the toilet a lot, being really thirsty, feeling more tired than usual, losing weight or looking thinner than usual) being the most prevalent symptoms. Non-specific signs and symptoms are also possible, and delaying or missing the diagnosis can have a devastating effect on a child's health. Children with a definitive diagnosis of diabetes often require medical treatment for problems such as ketoacidosis, hypoglycemia and hyperglycemia. To reach glycated hemoglobin (HbA1c) values of 48 mmol/mol, lifetime rigorous monitoring and management of blood glucose levels via insulin replacement treatment is needed in T1D. Physical and psychosocial issues arise frequently with a diabetes diagnosis, resulting in poor management. Nurses play a significant role in detecting diabetes in a number of healthcare settings, resulting in quick diagnoses and prompt initiation of treatment. Not only do they provide critical assistance to help children and their families with the diagnosis, they also place particular emphasis on managing difficult days and common problems with ongoing management. Nurses can provide invaluable assistance managing this chronic condition by coping with day-to-day challenges.

Nursing Care Plan and Management of Patients With Acute Leukemia.

OBJECTIVE: To provide an overview of the integration of nursing care services for patients with acute leukemia in the past, present and future. DATA SOURCES: Published literature as indexed in Medline, relevant guideline documents, textbooks and clinical experience. CONCLUSION: Patients with acute leukemia have significant nursing care demands that are frequently unmet by routine oncology treatment. The initial introduction of expert nursing care into routine oncology treatment boosts patient-centered results in people with advanced solid tumors, according to research. Recent data suggest that patients with hematologic malignancies who have undergone transplantation of stem cells have similarly improved, and further trials are being conducted to assess nursing care treatments in patients with acute leukemia. NURSING PRACTICE IMPLICATIONS: Nurses are essential in the management of patients with acute leukemia both in and out of the hospital. As a result, having a basic understanding of these illnesses is critical. In the management of oncologic crises, early symptom identification is crucial.

CT-Based Sarcopenic Nomogram for Predicting Progressive Disease in Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: It is prudent to identify the risk for progressive disease (PD) in patients with non-small-cell lung cancer (NSCLC) who undergo platinum-based chemotherapy. The present study aimed to develop a CT imaging-based sarcopenic nomogram for predicting the risk of PD prior to chemotherapy treatment. METHODS: We retrospectively enrolled patients with NSCLC who underwent platinum-based chemotherapy. Imaging-based body composition parameters such as skeletal muscle index (SMI) for assessment of sarcopenia were obtained from pre-chemotherapy chest CT images at the level of the eleventh thoracic vertebral body (T11). Sarcopenic nomogram was constructed using multivariate logistic regression and performance of the nomogram was evaluated by discrimination, calibration curve, and decision curve. RESULTS: Sixty (14.7%) of the 408 patients in the study cohort developed PD during chemotherapy. The prediction nomogram for developing PD achieved a moderate efficiency with an area under the curve (AUC) of 0.75 (95% CI: 0.69-0.80) for the training cohort, and 0.76 (95%CI: 0.68-0.84) for the validation cohort, as well as a good performance of consistence (bootstrap for training cohort: 0.75 ± 0.02; validation cohort: 0.74 ± 0.06). Favorable clinical application was observed in the decision curve analysis. CONCLUSION: Our CT-based sarcopenic nomogram showed the potential for an individualized prediction of progression for patients with NSCLC receiving platinum-based chemotherapy.

The Preoperative Diagnostic Value of MRI and Otoneural Tests in Acoustic Neuroma.

OBJECTIVES: To determine the preoperative diagnostic accuracy of MRI and otoneural tests (ONT) for acoustic neuroma (AN) in a cohort of unselected patients with pontocerebellar angle tumors. To find a convenient way to screening out the potential asymptomatic AN patient earlier. DESIGN: This diagnostic accuracy study was performed in a central hospital and included a consecutive sample of unilateral incipient pontocerebellar angle tumor patients referred for MRI and ONT before surgery. Different AN features of MRI and ONT were collected and concluded into preoperative diagnostic variables or variable combinations. Those of MRI and ONT are analyzed and compared with biopsy results by multivariable receiver operating characteristic (ROC) analysis. The early-stage group, the course of which is 1 year or less, was separately computed and compared. RESULTS: Eighty-three subjects were collected from June 2013 to June 2019; 62 were confirmed AN postoperatively by biopsy, whereas others are not AN. The area under the curve (AUC) of MRI was 0.611, whereas the AUC of ONT was 0.708. In the early-stage group, the AUC of MRI was 0.539, and the AUC of ONT was 0.744. CONCLUSIONS: ONT was able to identify more subjects affected by unilateral incipient AN than MRI preoperatively. Given that ONT is a functional test for internal auditory canal nerves, it is an optimal screening test for AN patients because it provides more information than MRI for the further clinical plan. It is particularly noteworthy for identifying asymptomatic AN patients and for early stage. Therefore, it may help more patients from unnessesary surgery. Furthermore, an MRI follow-up is suggested if the patient was found alert in ONT.

Neurodevelopment correlates with gut microbiota in a cross-sectional analysis of children at 3 years of age in rural China.

We investigated cross-sectional associations between children's neurodevelopment and their gut microbiota composition. Study children (36 months of age) lived in rural China (n = 46). Neurodevelopment was assessed using the Bayley Scales of Infant Development, 2nd Edition, yielding the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Children's gut microbiota was assessed using 16S rRNA gene profiling. Microbial diversity was characterized using alpha diversity patterns. Additionally, 3 coabundance factors were determined for the 25 most abundant taxa. Multivariable linear regression models were constructed to examine the relationships between Bayley scores (MDI and PDI) and children's gut microbiota. In adjusted models, MDI and PDI scores were not associated with alpha diversity indices. However, in adjusted models, MDI and PDI scores were positively associated with the first coabundance factor, which captured positive loadings for the genera Faecalibacterium, Sutterella, and Clostridium cluster XIVa. For an interquartile range increase in the first coabundance factor, MDI scores increased by 3.9 points [95% confidence interval (CI): 0, 7.7], while PDI scores increased by 8.6 points (95% CI 3.1, 14). Our results highlight the potential for gut microbial compositional characteristics to be important correlates of children's Bayley Scales performance at 36 months of age.

The long-term follow-up of 61 horizontal canal BPPV after Gufoni and Barbecue maneuver: a prospective study.

Background: Horizontal canal BPPV (HC-BPPV) has a higher recurrence rate than PC-BPPV. Which maneuver is better for its prognosis is still uncertain.Objective: To compare the long-term recurrence rate after Gufoni and Barbecue maneuver.Materials and methods: We prospectively collected 61 cases of HC-BPPV which were initially diagnosed in our hospital from the first episode, and had already ruled out other diseases. Roll them into Gufoni group and Barbecue group alternatively. After the maneuver, we followed them up until December 2016. Mean follow-up time was 49.25 months.Results: The recurrence rate is 18.0% in the first year, 14.8% after the first year, and 31.1% overall. There is no statistically significant difference between Gufoni group and Barbecue group (p > .05). Age is statistically significant as a risk factor of recurrence (p<.05).Conclusions and significance: Barbecue maneuver is as good as Gufoni maneuver. The recurrence rate is only related to age. We suggest the disease relapsed within the 1st year as recurrence rather than a new disease.

Quantification of Human Oral and Fecal Streptococcus parasanguinis by Use of Quantitative Real-Time PCR Targeting the groEL Gene.

Two pairs of species-specific PCR primers targeting the housekeeping groEL gene, Spa146f-Spa525r and Spa93f-Spa525r, were designed to quantify human oral and fecal Streptococcus parasanguinis. Blast analysis against reference sequences of NCBI nucleotide collection database and the Chaperonin Sequence Database showed the forward primers Spa146f and Spa93f 100% matched only with S. parasanguinis, and the in silico Simulated PCR algorithm showed both primer pairs hit only S. parasanguinis groEL gene in Chaperonin Sequence Database. The two primer pairs were respectively used to perform PCR with saliva DNA of each of 6 human subjects, and the amplicons of individual PCR reactions were cloned. The phylogenetic analysis showed cloned sequences were all affiliated to S. parasanguinis, which further validates the specificity of two primer pairs, and that individual subjects harbored multiple genotypes of S. parasanguinis in saliva. By spiking S. parasanguinis into human fecal samples, we found the quantification limit of quantitative real-time PCR (qPCR) assays for both primer pairs was 5-6 log10 groEL copies/g feces. Human fecal S. parasanguinis amounts quantified with qPCR using each of the two primer pairs correlated well with those determined with metagenomic sequencing. qPCR with either primer pair showed periodontitis patients had significantly lower level of saliva S. parasanguinis than healthy people. In both feces and saliva, the S. parasanguinis abundances quantified with two primer pairs exhibited strong and significant correlation. Our results show that the two S. parasanguinis-specific primer pairs can be used to quantify and profile human saliva and fecal S. parasanguinis.

Malignant transformation potentials of human umbilical cord mesenchymal stem cells both spontaneously and via 3-methycholanthrene induction.

Human umbilical cord mesenchymal stem cells (HUMSCs) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers. Thus, HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering. However there are reports on spontaneous transformation of mesenchymal stem cells (MSCs) derived from human bone marrows. The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown. Therefore, we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene (3-MCA), a DNA-damaging carcinogen. The malignant transformation of HUMSCs in vitro was evaluated by morphological changes, proliferation rates, ability to enter cell senescence, the telomerase activity, chromosomal abnormality, and the ability to form tumors in vivo. Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. When these cells (tHUMSCs) were injected into immunodeficient mice, they gave rise to sarcoma-like or poorly differentiated tumors. Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro. Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation. However, the malignant transformation could be induced by chemical carcinogen 3-MCA.