Plasma metabolite biomarkers related to secondary hyperparathyroidism and parathyroid hormone.

BACKGROUND: Hyperphosphatemia, hypocalcemia, and elevation of parathyroid hormone (PTH) are typical abnormalities of uremic patients with Secondary hyperparathyroidism (SHPT). However, metabolic imbalance associated with SHPT is not well understood. METHODS: A total of 15 SHPT patients with an intact parathyroid hormone (iPTH) level > 600 pg/mL were set as preoperative (PR) group, 15 age- and gender-matched controls who had undergone parathyroidectomy plus forearm transplantation because of hyperparathyroidism and achieved an iPTH level <150 pg/mL were set as postoperative (PO) group. Metabolite profiling of these 30 uremic patients and five healthy controls (HC) was performed using ultra performance liquid chromatography-mass spectrometry. RESULTS: Five differential metabolites, including allyl isothiocyanate, L-phenylalanine, D-Aspartic acid, indoleacetaldehyde, and D-galactose correlated with PTH were identified in this study. Taking them as a biomarker signature, PR group can be distinguished from HC group with an area under the curve (AUC) of 0.947 (95% CI, 0.76-1) and PO group with an AUC of 0.6 (95% CI, 0.38-0.807). CONCLUSIONS: The serum metabolome correlated with PTH is successfully demonstrated for a better understanding of the pathogenesis of SHPT.

The Mitochondria-Targeted Metabolic Tubular Injury in Diabetic Kidney Disease.

BACKGROUND/AIMS: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide, and the importance of tubular injury has been highlighted in recent years. However, the underlying mechanisms and effective therapeutic targets are still unclear. In this study, we investigated mtDNA, mitochondrial dynamics, function and metabolic pathways to determine if mitochondrial damage plays a critical role in the development of tubular injury in DKD patients. METHODS: A cross-sectional study was carried out among healthy controls (HCs, n = 65), diabetes patients without kidney disease (DCs, n = 48) and DKD patients (n = 60). Serum, peripheral blood mononuclear cells (PBMCs) and kidney biopsy specimens were obtained from participants. Metabolomics was employed to investigate cellular metabolism. RESULTS: DKD patients had decreased mtDNA copy numbers and increased mtDNA damage compared to DCs. Mitochondrial fragmentation was specifically presented in tubules, but not in podocytes of DKD patients. The accumulation of damaged mtDNA and fragmented mitochondria resulted in increased reactive oxygen species (ROS) generation, activation of apoptosis and loss of mitochondrial membrane potential (ΔΨm) in tubules and PBMCs. Furthermore, glycolysis and tricarboxylic acid (TCA) cycle was perturbed, and increased dihydroxyacetone phosphate (DHAP) and decreased succinyl-CoA synthetase (SCS) respectively in these two metabolic pathways were identified as potential biomarkers for tubular injury in DKD. CONCLUSION: Our study indicates that mitochondrial damage could be the hallmark of tubular injury in DKD patients, and this would provide a novel and attractive therapeutic target to improve this disease.

Nasal congestion caused by long-term retention of a nasal foreign body near the orbit: A case report.

BACKGROUND: Nasal trauma presents a risk of foreign body invasion into the nasal cavity. However, in the early treatment stage of nasal trauma, patients and doctors are not always aware of possible foreign body invasion, resulting in delayed detection. We describe the case of an adult patient admitted to the hospital due to left nasal congestion accompanied by yellow, purulent, and bloody discharge. CASE SUMMARY: Consultation with the patient revealed a history of nasal trauma 30 years prior that did not receive thorough examinations and imaging during treatment, resulting in a glass fragment retained in the nasal cavity adjacent to the orbit. After admission, computerized tomography (CT) confirmed the presence of the foreign body in the patient's left nasal-maxillary sinus. The nasal foreign body led to symptoms such as chronic sinusitis, nasal polyps, fungal infection, and deviated nasal septum. The foreign body was successfully removed by nasal endoscopy, polypectomy, sinus fungal removal, left middle turbinate conchoplasty, fenestration via the right inferior meatus, nasal endoscopic maxillary sinus cystectomy, and septolplasty. The operation was successful and without any complications. CONCLUSION: CT scans should be performed in addition to necessary debridement sutures to avoid possible foreign body invasion during nasal trauma. Surgical planning should be tailored to the patient's specific situation. The surgical method should be carefully selected, and sufficient preparation should be undertaken before the surgery to avoid possible displacement of the nasal foreign body.

Effect of different dentin moisture on the push-out strength of bioceramic root canal sealer.

Background/purpose: Different moisture condition may affect the adhesion between obturation materials and root canal walls, thus further affect the quality of root canal obturation. The aim of this study was to evaluate the influence of dentin moisture conditions after different root canal drying protocols on the push-out strength of bioceramic root canal sealer. Materials and methods: Twenty root canals from extracted human decoronated premolars were prepared in vitro to #30/0.09 taper and assigned to 4 moisture condition groups after using different root canal drying protocols: normal moisture (paper point) group: the canals were blot dried with paper points until the last one appeared dry. Ethanol dry group: the canals were dried with paper points followed by dehydration with 95% ethanol. Isopropanol dry group: the canals were dried with paper points followed by dehydration with 70% isopropanol. Complete dry group: the canals were dried in an air-blowing thermostatic oven for at least 6 h until there was no change in weight at an interval of 1 h. After drying, the canals were obturated with bioceramic sealer iRoot SP. Then, each root was sectioned into eight slices with 1-mm-thick using a diamond saw (40 slices each group). The push-out strength was tested for each slice between the sealer and dentin wall using a universal testing machine at a crosshead speed of 0.5 mm/min, and failure modes were recorded. Two-way analysis of variance and Tukey test were used to analyze the push-out strength. Logarithmic linear regression analysis was used to compare the failure modes. Results: Push-out strength was statistically different in different moisture groups (P < 0.05). After drying using paper point, iRoot SP specimens showed the highest push-out strength (2.04 ± 0.03 MPa), followed by 95% ethanol, 70% isopropanol. The lowest push-out strength (0.68 ± 0.04 MPa) was observed under complete dry. For the failure modes, the majority were cohesive failures in the coronal and middle thirds of the root; while in the apical third, mixed failure was common. Conclusion: Different drying protocols influenced the push-out strength between bioceramic sealer and canal wall.

A surgical nursing perspective analysis of glucose variability in BCLC stage B-C hepatocellular carcinoma patients with and without T2D within 1 year of hepatectomy: a retrospective cohort study from 2016 to 2020.

Background: Previous research has reported that variability in glucose levels is associated with a variety of patient characteristics in colon cancer. However, relevant research is still lacking in relation to hepatocellular carcinoma (HCC). Methods: A total of 95 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B-C who underwent liver resection at the Eastern Hepatobiliary Surgery Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were included in this study. The patients were divided into 2 groups with type 2 diabetes (T2D) and without T2D. The primary outcome variable was blood glucose variability at 1 month and within 1 year of HCC surgery. Results: In this study, the age of patients with T2D was greater than that of patients without T2D (mean age: 70.3±8.45 vs. 60.4±11.27 years, P=0.031). Compared to the patients without T2D, those with T2D had higher blood glucose measurements within 1 month (33 vs. 7) and 1 year (46.5 vs. 22.5, P<0.001) of surgery. The T2D patients and non-T2D patients did not differ in terms of chemotherapy medication or other characteristics. Among the 95 patients with BCLC stage B-C HCC, those with T2D had higher variability in glucose levels (P<0.001) than those without T2D within 1 month of surgery [standard deviation (SD) =46.43 mg/dL, coefficient of variation (CV) =23.5% vs. SD =21.56 mg/dL, CV =13.21%], and within 1 year of surgery (SD =42.49 mg/dL, CV =26.14% vs. SD =20.45 mg/dL, CV =17.36%). A correlation was found between a lower body mass index and higher variability in glucose levels within 1 month of surgery among patients with T2D [SD (r=-0.431, P<0.05) and CV (r=-0.464, P<0.01)]. A higher preoperative blood glucose level in T2D patients was correlated with a higher blood glucose variability within 1 year of surgery (r=0.435, P<0.01). Variability in glucose levels was weakly correlated with the demographic and clinical characteristics of patients who do not have T2D. Conclusions: HCC patients with T2D in BCLC stage B-C showed greater variability in glucose levels within 1 month and 1 year of surgery. Preoperative hyperglycemia, insulin use, and a lower cumulative dose of steroids were clinical features correlated with a higher variability in glucose levels in T2D patients.

Serum Uric Acid Levels in Neurodegenerative Disorders: A Cross-Sectional Study.

BACKGROUND: Excessive oxidative stress may contribute to neurodegeneration by leading to protein aggregation and mitochondrial dysfunction. Uric acid (UA) is an important endogenous antioxidant that protects against oxidative stress, yet its exact role in neurodegeneration remains unclear. OBJECTIVE: To explore the performance of serum UA in neurodegenerative disorders. METHODS: A total of 839 controls and 840 patients, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), motor neuron disease (MND), Creutzfeldt-Jakob disease (CJD), and mixed dementia (MixD) were enrolled. Fasting serum UA levels were measured in all participants and compared between patients and controls. Linear regression models were utilized to explore possible relationships of serum UA with cognition, disease duration, age, and age of onset. RESULTS: Compared to controls (355.48 ±â€Š85.38 µmol/L), serum UA was significantly lower in AD (291.29 ±â€Š83.49 µmol/L, p < 0.001), PD (286.95 ±â€Š81.78 µmol/L, p < 0.001), PSP (313.32 ±â€Š88.19 µmol/L, p < 0.001), FTD (313.89 ±â€Š71.18 µmol/L, p = 0.001), and DLB (279.23 ±â€Š65.51 µmol/L, p < 0.001), adjusting for confounding factors including age, gender, education, etc. In addition, serum UA was positively correlated with cognitive levels in all patients (Mini-Mental State Examination: r = 0.136, p = 0.001; and Montreal Cognitive Assessment Scale: r = 0.108, p = 0.009). CONCLUSION: Decreased levels of serum UA were correlated with AD, PD, PSP, FTD, and DLB, offering significant potential as a promisingly relevant, less-invasive marker of multiple neurodegenerative disorders.

Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis.

This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30-90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13-3.37, P = 0.016) for PFS and 2.70 (95% CI: 1.81-4.02, P < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5-1.7) and 8.8 months (95% CI: 8.5-9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.

The incidence of gastrointestinal adverse events in patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1 inhibitors: a meta-analysis.

BACKGROUND: We conducted a meta-analysis to evaluates the incidence of the gastrointestinal (GI) adverse events with the use of PD-1 inhibitors among patients with advanced non-small cell lung cancer (NSCLC). METHODS: The PICOs (participants, intervention, comparison, and outcomes) elements were used for the selection of studies to meet the inclusion and exclusion criteria. Google Scholar, PubMed, Science Direct and proceedings of major oncology conferences were systematically searched from their inception to December 2020, to identify studies which reported the GI adverse events of PD-1 inhibitors among patients with NSCLC. Risks of bias were assessed by using a revised methodological index for nonrandomized studies (MINORS). Pooled incidences and weighted relative risk (RR) estimate for GI adverse events, the incidence of treatment discontinuation due to GI adverse events was also calculated. To perform the analysis of qualified studies, the model of random effects was used and the inconsistency of studies with the I2 index was investigated. OpenMeta 10.10, Stata 11.0 and RevMan 5.3 software were used for data analysis. RESULTS: The research included 15 studies comprising of a total of 3,716 patients. The incidences of all-grade GI symptoms were: diarrhea 8.6% (95% CI: 6.6-10.6%), nausea 9.2% (95% CI: 7.3-11.0%), vomiting 3.2% (95% CI: 1.9-4.5%), constipation 2.8% (95% CI: 1.8-3.9%), colitis 0.7% (95% CI: 0.4-1.1%), stomatitis (95% CI: 1.0-2.7%), and decreased appetite 10.0% (95% CI: 8.3-11.7%). Therapy using PD-1 inhibitors was discontinued in 2.5% (95% CI: 0.0-5.1%) of patients with nausea, in 3.0% (95% CI: 0.7-5.3%) of those with diarrhea, and in 45.7% (95% CI: 20.6-70.7%) of patients with colitis. Compared with chemotherapy, the use of PD-1 inhibitors showed significant increase in the occurrence of grade 1-4 colitis (RR =3.90, 95% CI: 1.41-10.81, P=0.009) and grade 3-4 colitis (RR =3.76, 95% CI: 1.07-13.26, P=0.04). DISCUSSION: This meta-analysis provides a reliable estimate of the incidences of GI adverse events among NSCLC patients. Especially when colitis does occur, it often results in therapy discontinuation. Use of PD-1 inhibitors led to a higher incidence of colitis as compared to the use of chemotherapy.

The Study of Angptl4-Modulated Podocyte Injury in IgA Nephropathy.

BACKGROUND: Increasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet. METHODS: Plasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed. RESULTS: Thirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, FOS and G6PC were found to be upregulated in IgAN patients, while MMP9 was downregulated in IgAN patients. Plasma and urine Angptl4 levels were closely related to the degree of podocyte injury and urine protein, but not to the protein-creatine ratio. CONCLUSION: Our findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD.

Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway.

Organ dysfunction caused by sepsis is life-threatening and results in high mortality. Therapeutic options for sepsis are limited. Pathogenic factors are considered as components of environmental pressure that modify DNA methylation patterns thereby enhancing disease progression. Here, we found that sepsis patients exhibited higher levels of genomic DNA methylation patterns and hypermethylated genes associated with the NF-kB signaling pathway. Therefore, we hypothesized that a DNA methyl transferase inhibitor, Decitabine, may mitigate inflammation and improve survival by inhibiting the NF-κB signaling pathway. To test the hypothesis, mice challenged with caecal ligation and puncture (CLP) were subcutaneously injected with Decitabine solution (0.5, 1, and 1.5 mg/kg) 2 h following operation. Our results indicated that Decitabine reduces DNA methyltransferases (DNMTs), attenuates NF-κB activation, downregulates inflammatory cytokine levels, and inhibits the progression of sepsis. Thus, DNA methylation may be indispensable for sepsis and serve as a predicting factor. The use of Decitabine could represent a novel strategy in the treatment of sepsis.

The pathogenic AGT c.856+1G>T mutation of a patient with multiple renal cysts and hypertension.

Angiotensinogen (AGT) is an essential member of the renin-angiotensin system (RAS); this system regulates blood pressure and affects the physiological function of the kidney. Studies found that mutations of the human AGT gene are involved in diseases such as recessive renal tubular dysgenesis (RTD) and essential hypertension (EHT). Here, we report a 29-year-old male Chinese with essential hypertension and cystic kidney disease. Exome sequencing analysis of the patient and his parents revealed a mutation in the splice donor site of intron 2 of the AGT gene, c.856+1G>T. This mutation was a heterozygous form and inherited from his mother, and the mother was diagnosed with essential hypertension lasting over 20 years. Function prediction of c.856+1G>T mutation using online software showed this intron mutation may affect protein features by destroying the normal splice site. These findings suggest that this intron mutation of the AGT gene is related to the patient's essential hypertension and cystic kidney disease.

Lack of association between ADRA2B-4825 gene insertion/deletion polymorphism and migraine in Chinese Han population.

OBJECTIVE: The present study aimed to estimate the association between susceptibility to migraine and the 12-nucleotide insertion/deletion (indel) polymorphism in promoter region of alpha(2B)-adrenergic receptor gene (ADRA2B). METHODS: A case-control study was carried out in Chinese Han population, including 368 cases of migraine and 517 controls. Genomic DNA was extracted from blood samples, and DNA fragments containing the site of polymorphism were amplified by PCR. Data were adjusted for sex, age, migraine history and family history, and analyzed using a logistic regression model. RESULTS: There was no association between indel polymorphism and migraine, at either the allele or the genotype level. CONCLUSION: These findings do not support a functional significance of ADRA2B indel polymorphism at position -4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects.