Global, Regional, and National Burden of CKD in Children and Adolescents from 1990 to 2019.

BACKGROUND AND AIMS: CKD is one of the most prevalent non-communicable health concerns in children and adolescents worldwide; however, data on its incidence, prevalence, disability-adjusted life years (DALYs), and trends in the population are limited. We aimed to assess the global, regional, and national trends in CKD burden in children and adolescents. METHODS: In this trend analysis based on the 2019 Global Diseases, Injuries, and Risk Factors Study, CKD incidence, prevalence, and DALYs rates per 100,000 population for children and adolescents were reported at the global, regional, and national levels, as well as the average annual percentage change (AAPC). These global trends were analyzed by age, sex, region, and socio-demographic index (SDI). RESULTS: Globally, the overall incidence of CKD (all stages including KRT) in children and adolescents showed an increasing trend (AAPC 0.44 [95% CI 0.36-0.52]) between 1990 and 2019. Similarly, the overall prevalence of CKD also showed an upward trend (AAPC 0.46 [95% CI 0.42-0.51]). However, the DALYs of CKD showed a continuous decreasing trend (AAPC -1.18[-1.37- -0.99]). The population aged 15-19 years had the largest CKD incidence increase during this period. The largest increase in age-standardized incidence rate (ASIR) was in middle SDI countries (AAPC 0.56 [0.45-0.67]). The relationship between the ASIR and SDI showed an inverse U-shaped correlation while the relationship between the age-standardized DALYs rate (ASDR) and SDI showed an inverse trend with SDI. Among adolescents (15-19 years), the ASIR continued to increase for five causes of CKD, owing to type 2 diabetes mellitus and hypertension. Most of the disease burden was concentrated in countries with a lower SDI. Andean Latin America and Central Latin America showed the largest increases in CKD ASIR between 1990 and 2019. CONCLUSION: The burden of CKD in children and adolescents has increased worldwide, especially in regions and countries with a lower SDI.

A mobile terminal application program was used for endotracheal tube cuff pressure measurement.

We studied the application of a mobile terminal application program in endotracheal tube (ETT) cuff pressure measurement to improve the implementation rate of scientific ETT cuff pressure measurement and to ensure that the pressure falls within the recommended range. A pre-post controlled study lasting for 18 months was undertaken in a 40-bed general intensive care unit (GICU). This included a 6-month baseline period (baseline group) and a 6-month intervention period (intervention group). The mobile terminal application program was applied to monitor the cuff pressure of endotracheal intubation as an intervention measure during the intervention period. ETT pressure was the main outcome measure, while gender, age, causes for ICU admission, sedation score, duration of prior intubation, size of ETT, and number of VAP patients were secondary outcomes. ETT cuff pressure was monitored 742 times in both the baseline group and the intervention group. A total of 56.9% of the cuff pressure measurements in the baseline group were within the recommended range, while 78.4% of measurements in the intervention group were within the recommended range, reflecting a statistically significant difference (P < 0.05). The application of the mobile terminal application program used for ETT cuff pressure measurement could improve the percentage of ETT cuff pressure measurements falling within the recommended range.

Diosmin ameliorates renal fibrosis through inhibition of inflammation by regulating SIRT3-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Renal fibrosis is considered an irreversible pathological process and the ultimate common pathway for the development of all types of chronic kidney diseases and renal failure. Diosmin is a natural flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether Diosmin protects kidneys by inhibiting renal fibrosis is unknown. We aimed to investigate the role of Diosmin in renal interstitial fibrosis and to explore the underlying mechanisms. METHODS: The UUO mouse model was established and gavaged with Diosmin (50 mg/kg·d and 100 mg/kg·d) for 14 days. HE staining, Masson staining, immunohistochemistry, western blotting and PCR were used to assess renal tissue injury and fibrosis. Elisa kits were used to detect the expression levels of IL-1ß, IL-6, and TNF-α and the activity of SIRT3 in renal tissues. In addition, enrichment maps of RNA sequencing analyzed changes in signaling pathways. In vitro, human renal tubular epithelial cells (HK-2) were stimulated with TGF-ß1 and then treated with diosmin (75 µM). The protein and mRNA expression levels of SIRT3 were detected in the cells. In addition, 3-TYP (selective inhibitor of SIRT3) and SIRT3 small interfering RNA (siRNA) were used to reduce SIRT3 levels in HK-2. RESULTS: Diosmin attenuated UUO-induced renal fibrosis and TGF-ß1-induced HK-2 fibrosis. In addition, Diosmin reduced IL-1ß, IL-6, and TNF-α levels in kidney tissues and supernatants of HK-2 medium. Interestingly, Diosmin administration increased the enzymatic activity of SIRT3 in UUO kidneys. In addition, Diosmin significantly increased mRNA and protein expression of SIRT3 in vitro and in vivo. Inhibition of SIRT3 expression using 3-TYP or SIRT3 siRNA abolished the anti-inflammatory effects of diosmin in HK-2 cells. Enrichment map analysis by RNA sequencing indicates that the nuclear factor-kappa B (NF-κB) signaling pathway was inhibited in the Diosmin intervention group. Furthermore, we found that TGF-ß1 increased the nuclear expression of nuclear NF-κB p65 but had little significant effect on the total intracellular expression of NF-κB p65. Additionally, Diosmin reduced TGF-ß1-caused NF-κB p65 nuclear translocation. Knockdown of SIRT3 expression by SIRT3 siRNA increased the nuclear expression of NF-κB p65 and abolished the inhibition effect of Diosmin in NF-κB p65 expression. CONCLUSIONS: Diosmin reduces renal inflammation and fibrosis, which is contributed by inhibiting nuclear translocation of NF-κB P65 through activating SIRT3.

Analysis of the potential biological mechanisms of diosmin against renal fibrosis based on network pharmacology and molecular docking approach.

BACKGROUND: Interstitial fibrosis is involved in the progression of various chronic kidney diseases and renal failure. Diosmin is a naturally occurring flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether diosmin protects kidneys by inhibiting renal fibrosis is unknown. METHODS: The molecular formula of diosmin was obtained, targets related to diosmin and renal fibrosis were screened, and interactions among overlapping genes were analyzed. Overlapping genes were used for gene function and KEGG pathway enrichment analysis. TGF-ß1 was used to induce fibrosis in HK-2 cells, and diosmin treatment was administered. The expression levels of relevant mRNA were then detected. RESULTS: Network analysis identified 295 potential target genes for diosmin, 6828 for renal fibrosis, and 150 hub genes. Protein-protein interaction network results showed that CASP3, SRC, ANXA5, MMP9, HSP90AA1, IGF1, RHOA, ESR1, EGFR, and CDC42 were identified as key therapeutic targets. GO analysis revealed that these key targets may be involved in the negative regulation of apoptosis and protein phosphorylation. KEGG indicated that pathways in cancer, MAPK signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway were key pathways for renal fibrosis treatment. Molecular docking results showed that CASP3, ANXA5, MMP9, and HSP90AA1 stably bind to diosmin. Diosmin treatment inhibited the protein and mRNA levels of CASP3, MMP9, ANXA5, and HSP90AA1. Network pharmacology analysis and experimental results suggest that diosmin ameliorates renal fibrosis by decreasing the expression of CASP3, ANXA5, MMP9, and HSP90AA1. CONCLUSIONS: Diosmin has a potential multi-component, multi-target, and multi-pathway molecular mechanism of action in the treatment of renal fibrosis. CASP3, MMP9, ANXA5, and HSP90AA1 might be the most important direct targets of diosmin.

Effects of enhanced starch-xanthan gum synergism on their physicochemical properties, functionalities, structural characteristics, and digestibility.

The limited and unstable interactions between potato starch (PS) and xanthan gum (XG) by simple mixing (SM) lead it difficult to induce substantial changes in starchy products. Structural unwinding and rearrangement of PS and XG by critical melting and freeze-thawing (CMFT) were used to promote PS/XG synergism, and the physicochemical, functionalities, and structural properties were investigated. Compared to "Native" and SM, CMFT promoted the formation of large clusters with a rough granular surface and wrapped by a matrix composed of released soluble starches and XG (SEM), thus making the composite more compact to thermal processes, such as the significantly decreased WSI and SP, and increased the melting temperatures. The enhanced synergism of PS/XG after CMFT effectively decreased the breakdown viscosity from ~3600 (Native) to ~300 mPa·s and increased the final viscosity from ~2800 (Native) to ~4800. CMFT significantly increased the functional properties of PS/XG composite, including water/oil absorptions and resistant starch content. CMFT caused the partial melting and loss of large packaged structures in starch (XRD, FTIR, and NMR), and the melting and the loss of crystalline structure controlled at approximately 20 % and 30 %, respectively, are the most effective for promoting PS/XG interaction.

Effect of melting combined with ice recrystallization on porous starch preparation: Pore-forming properties, granular morphology, functionality, and multi-scale structures.

In this work, critical melting (CM) combined with freeze-thawing treatment (FT, freezing at -20 â„ƒ and -80 â„ƒ, respectively) was used to prepare porous starch. The results showed that CM combined with the slow freezing rate (-20 â„ƒ) can prepare porous starch with characteristics of grooves and cavities, while combined with the rapid freezing rate (-80 â„ƒ) can prepare with holes and channels, especially after repeating FT cycles. Compared with the native counterpart, the specific surface area, pore volume, and average diameter of CMFT-prepared porous starch were significantly increased to 4.07 m2/g, 7.29 cm3/g × 10-3, and 3.57 nm, respectively. CMFT significantly increased the thermal stability of starch, in which the To, Tp, and Tc significantly increased from 63.32, 69.62, and 72.90 (native) to ∼69, 72, and 76 °C, respectively. CMFT significantly increased water and oil absorption of porous starch from 91.20 % and 72.00 % (native) up to ∼163 % and 94 %, respectively. Moreover, CMFT-prepared porous starch had a more ordered double-helical structure, which showed in the significantly increased relative crystallinity, semi-crystalline lamellae structure, and the proportion of the double helix structure of starch. The synergistic effect of melting combined with ice recrystallization can be used as an effective way to prepare structure-stabilized porous starch.

Improvement of pasting and gelling behaviors of waxy maize starch by partial gelatinization and freeze-thawing treatment with xanthan gum.

To improve the pasting and gelling behaviors of waxy maize starch, an aqueous dispersion with or without xanthan gum was subjected to partial gelatinization (5 ℃ above the onset melting temperature of starch) and freeze-thawing treatment. After the treatments, starch granules were slightly deformed, with partial loss of birefringence, and tended to aggregate. The relative crystallinity and thermal stability of waxy maize starch crystals decreased by the treatments. These changes indicated that the treatment affected the inner structure and chain arrangement of the granules. The treated waxy maize starches, however, showed a higher overall pasting viscosity with shorter and more cohesive pastes than that of the native starch. The treated starches formed rigid gels with increased stability against freeze-thawing. The addition of small amounts of xanthan gum enhanced the effects of the treatments.

Environmental factors influencing the risk of ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterized by inflammation and destruction of small and medium-sized blood vessels. Clinical disease phenotypes include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The incidence of AAV has been on the rise in recent years with advances in ANCA testing. The etiology and pathogenesis of AAV are multifactorial and influenced by both genetic and environmental factors, as well as innate and adaptive immune system responses. Multiple case reports have shown that sustained exposure to silica in an occupational environment resulted in a significantly increased risk of ANCA positivity. A meta-analysis involving six case-control studies showed that silica exposure was positively associated with AAV incidence. Additionally, exposure to air pollutants, such as carbon monoxide (CO), is a risk factor for AAV. AAV has seasonal trends. Studies have shown that various environmental factors stimulate the body to activate neutrophils and expose their own antigens, resulting in the release of proteases and neutrophil extracellular traps, which damage vascular endothelial cells. Additionally, the activation of complement replacement pathways may exacerbate vascular inflammation. However, the role of environmental factors in the etiology of AAV remains unclear and has received little attention. In this review, we summarized the recent literature on the study of environmental factors, such as seasons, air pollution, latitude, silica, and microbial infection, in AAV with the aim of exploring the relationship between environmental factors and AAV and possible mechanisms of action to provide a scientific basis for the prevention and treatment of AAV.

[Proton magnetic resonance spectroscopy of prefrontal lobe and thalamus in schizophrenics: correlation with clinical characteristics].

OBJECTIVE: To explore the characteristics of different subtypes of schizophrenics on prefrontal lobe and thalamus by proton magnetic resonance spectroscopy ((1)H-MRS) and its relationship. METHODS: From August 2007 to April 2010 at our center, a total of 159 schizophrenics fulfilling the third edition criteria of Chinese Classification of Mental Disorders (CCMD-III) were recruited. And prefrontal lobe and thalamus were evaluated by multi-voxel (1)H-MRS. There were 88 males and 71 females. There were first-episode (n = 54) and not-first-episode (n = 105), negative subtype (n = 125) and positive subtype (n = 34), medicated (n = 96) and non-medicated (n = 63) by different criteria. The levels of N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine compounds (Cr) were measured and the ratios of NAA/Cr and Cho/Cr determined. Positive and negative syndrome scale (PANSS) and Wisconsin card sorting test (WCST) were also assessed. Only 45 normal controls received (1)H-MRS. RESULTS: On left prefrontal lobe and left thalamus, the NAA/Cr ratios in different subtypes of patients were lower than those in normal controls (P < 0.05 or 0.01). The NAA/Cr ratios in patients of non-first-episode (1.48 ± 0.34), negative subtype (1.40 ± 0.35) and medicated (1.47 ± 0.36) on right thalamus were also lower than those in normal controls (1.62 ± 0.37, t = 2.25, 3.56, 2.28, P < 0.05 or P < 0.01). Compared with positive subtype schizophrenics, the NAA/Cr ratios in those of negative subtype on right thalamus were lower (1.40 ± 0.35 vs 1.60 ± 0.37, t = 2.92, P < 0.01). On right thalamus of non-medicated schizophrenics, there was a negative correlation between the duration of illness and the ratio of NAA/Cr (r = -0.38, P < 0.05) and a positive correlation between the duration of illness and the ratio of Cho/Cr (r = 0.43, P < 0.01). On right thalamus of negative subtype schizophrenics, the ratios of NAA/Cr were negatively correlated with the total score of PANSS and the score of negative factor respectively (r = -0.36, -0.40, P < 0.05). On left prefrontal lobe of different subtypes, the ratios of NAA/Cr were negatively correlated with the total score of PANSS, the score of negative factor, responses errors and persistent errors (P < 0.01) and positively correlated with completed categories and conceptual level responses (P < 0.05 or P < 0.01). CONCLUSION: Abnormalities in neuronal function and/or integrity are present on left prefrontal lobe and left thalamus in schizophrenics. And right thalamus is probably involved in non-first-episode subtype, negative subtype and non-medicated subtype. Different subtypes of schizophrenics may have different characteristics of (1)H-MRS due to the duration of illness and their clinical symptoms.

The research on long-term clinical effects and patients' satisfaction of gabapentin combined with oxycontin in treatment of severe cancer pain.

Gabapentin has been used as an adjuvant for treatment of cancer pain. Previous studies showed that opioids combined with gabapentin for management of cancer pain reduced the dosage of opioids.The objective of this study was to explore the clinical effect and patients' satisfaction of oxycontin combined with gabapentin in treatment of severe cancer pain. After titration of morphine, 60 severe cancer patients with visual analog score (VAS) more than 7 were randomly divided into trial group (n = 30) and control group (n = 30). The control group was administered oxycontin and placebo, and the trial group was given oxycontin and gabapentin. VAS score was recorded pre- and post-treatment; while daily dose of oxycontin, daily cost of pain relief and life quality score were observed 1 week, 1 month, 2 months, 3 months, and 6 months post-treatment. We found that daily dose of oxycontin 1 month post was comparable between the 2 groups (P > 0.05). Three months post, compared with control group (58.0 ±â€Š15.2 mg), average daily dose of oxycontin was significant lower in trial group (33.4 ±â€Š11 mg) (P < 0.001). Average daily cost of pain relief in trail group (34.5 ±â€Š10.2 RMB) was less than the control group (52.4 ±â€Š13.7 RMB) (P < 0.001). Life quality score increased in all of the patients in both group post-treatment (P < 0.05); while life quality score in trail group was greater than in control group 3 months (46.8 ±â€Š4.5 vs 43.5 ±â€Š4.6, P = 0.007) and 6 months (46.5 ±â€Š4.8 vs 41.4 ±â€Š4.3, P < 0.001) post-treatment. The incidence of drowsiness and dizziness was comparable between the 2 groups (P > 0.05), while the incidence of nausea and vomiting (P = 0.038), and constipation (P < 0.001) was higher in the control group.We concluded that oxycontin combined with gabapentin used in severe cancer pain management can control pain effectively, decreased the dose of oxycontin and the cost of cancer pain relief, and reduced the incidence of nausea and vomiting, and constipation, increased the life quality.