Diagnostic value of serum CRP, PCT and IL-6 in children with nephrotic syndrome complicated by infection: a single center retrospective study.

OBJECTIVE: The purpose was to look into the diagnostic value of serum CRP, PCT and IL-6 in children with nephrotic syndrome co-infection. METHODS: One hundred and forty-nine children with nephrotic syndrome who met the inclusion and exclusion criteria were included in this study. The children were divided into three groups: bacterial infection group, non-bacterial infection group, and non-infection group. The diagnostic value was analyzed and compared using the ROC curve. RESULTS: There was no statistically significant difference in the Leukocyte counts among three groups. The mean results of serum CRP, PCT and IL-6 were significantly higher in the bacterial infection group compared to those in the non-infection group (p < 0.05). AUC of CRP, PCT, IL-6 in bacterial infection were 0.791, 0.859, 0.783. The following combinations CRP + PCT + IL-6, IL-6 + PCT, CRP + PCT significantly increased the efficiency of bacterial infection diagnosis, the AUCs were 0.881, 0.884, and 0.884, respectively. AUC of PCT in non-bacterial infection was 0.663. The combinations of these three clinical indicators performed no better than PCT in ROC analysis. CONCLUSION: Normal CRP or IL-6 levels do not rule out the diagnosis of bacterial infection in children on long-term glucocorticoid therapy. The appropriate combination of two or three indicators can improve the diagnostic value. IMPACT: This study evaluated the diagnostic value of the serum concentrations of CRP, PCT and IL-6 and assessed whether the value of their combined application is better than when used alone for diagnosing primary nephrotic syndrome complicated by infection. The elevation in leukocyte count cannot be used to diagnose children with nephrotic syndromes on long-term glucocorticoid treatment who have bacterial infections. Normal CRP or IL-6 levels do not rule out the diagnosis of bacterial infection in children on long-term glucocorticoid therapy. The appropriate combination of two or three indicators can improve diagnostic value, sensitivity, and specificity.

The association between dental caries and steroid-sensitive nephrotic syndrome in children.

BACKGROUND: Pathogenesis and relapse of steroid-sensitive nephrotic syndrome (SSNS) are primarily associated with infection. Dental caries is the most common chronic progressive oral infection in children. However, clinical studies of SSNS combined with dental caries in children are rare. METHODS: In our retrospective cohort study from January 2021 to June 2022, 145 children with SSNS were included in the baseline analysis and 105 in the follow-up analysis. The follow-up period was 1 year. The primary study endpoints were the relapse-free period and frequently relapsing nephrotic syndrome (FRNS). Secondary endpoints included the number and triggers of relapses and concomitant medications. RESULTS: The median age was 5.5 years, with a caries rate of 60.7%, the mean DMFT/dmft was 3.86, and the caries filling rate was 1.6%. Except for the lower proportion of high household income and high parental education observed in the caries group, no statistical differences were found when comparing the other baseline data with the non-caries group. The caries group had a shorter relapse-free period and a lower 1-year cumulative relapse-free survival rate (HR = 1.90, 95% CI 1.17-3.09, P = 0.009). Univariate regression analysis showed caries associated with FRNS (OR = 2.714, 95% CI 1.021-7.219, P = 0.045), but the correlation no longer remained in the multivariate analysis. Additionally, seven cases of caries-derived pulpal periapical inflammation triggered SSNS relapses. The caries group had more infection triggers and concomitant medication use. CONCLUSION: Dental caries and relapse of SSNS are potentially associated, but careful evaluation is needed.

External validation of the pediatric International IgA Nephropathy Prediction Tool in a central China cohort.

BACKGROUND: This study aimed to externally validate the pediatric International IgA Nephropathy (IgAN) Prediction Tool updated from the adult IgAN Prediction Tool. METHODS: 439 children with biopsy-confirmed idiopathic IgAN were enrolled in this external validation study. The primary outcome was a 30% decline in eGFR or end-stage kidney disease. We evaluated the discrimination using Harrell's C-index, the receiver operating characteristic (ROC) curve, and Kaplan-Meier curves for four risk groups (< 16th [low risk], ∼16 to < 50th [intermediate risk], ∼50 to < 84th [high risk], and ≥ 84th percentiles [highest risk] of linear predictor). Calibration was assessed using calibration plots. RESULTS: The median follow-up time of the 439 patients was 4.5 (2.7-6.8) years, and 27 patients reached the primary outcome. Compared with the reported cohorts, our cohort was more contemporary, with milder proteinuria at biopsy, and had lower proportions of S1 and T1 lesions. Harrell's C-index and area under the ROC curve at 5 years were < 0.7 for both the models with and without race. The Kaplan-Meier curves of the risk groups were not well separated for the two models, only separated completely between the highest-risk group and the others for the model without race. The two models generally overestimated the risk of the primary outcome, CONCLUSION: The model without race could accurately distinguish the highest-risk patients from patients with low, intermediate, and high risk for kidney progression. Discrimination and calibration for the full model with or without race were unsatisfactory in this contemporary cohort in central China.

SPP1 is a prognostic related biomarker and correlated with tumor-infiltrating immune cells in ovarian cancer.

BACKGROUND: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of multiple cancer types However, it still awaits further exploration whether SPP1 is a bystander or an actual player in the modulation of immune infiltration in ovarian cancer. METHODS: In this study, the expression level of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and the result of SPP1 immumohistochemical staining was acquired by The HPA database. The impact of SPP1 expression level on the clinical outcome of ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were conducted using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database. To verify these findings from the public database, the results were validated in a cohort of ovarian cancer patients. RESULTS: SPP1 was found to be overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter survivals. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4 + T cells, CD8 + T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression level showed strong correlation with diverse immune cells in ovarian cancer. Of note, functional enrichment analysis suggested that SPP1 was strongly correlated with immune response. CONCLUSIONS: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer. TRIAL REGISTRATION: Not applicable.

Effects of continuous subcutaneous insulin infusion on the microstructures, mechanical properties and bone mineral compositions of lumbar spines in type 2 diabetic rats.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) for the treatment of type 2 diabetes (T2D) can improve the structure and strength of femur of rats, but the effect of CSII treatment on the lumbar spine of T2D rats is unknown. The purpose of this study is to investigate the effects of CSII on the microstructure, multi-scale mechanical properties and bone mineral composition of the lumbar spine in T2D rats. METHODS: Seventy 6-week-old male Sprague-Dawley (SD) rats were divided into two batches, each including Control, T2D, CSII and Placebo groups, and the duration of insulin treatment was 4-week and 8-week, respectively. At the end of the experiment, the rats were sacrificed to take their lumbar spine. Microstructure, bone mineral composition and nanoscopic-mesoscopic-apparentand-macroscopic mechanical properties were evaluated through micro-computed tomography (micro-CT), Raman spectroscopy, nanoindentation test, nonlinear finite element analysis and compression test. RESULTS: It was found that 4 weeks later, T2D significantly decreased trabecular thickness (Tb.Th), nanoscopic-apparent and partial mesoscopic mechanical parameters of lumbar spine (P < 0.05), and significantly increased bone mineral composition parameters of cortical bone (P < 0.05). It was shown that CSII significantly improved nanoscopic-apparent mechanical parameters (P < 0.05). In addition, 8 weeks later, T2D significantly decreased bone mineral density (BMD), bone volume fraction (BV/TV) and macroscopic mechanical parameters (P < 0.05), and significantly increased bone mineral composition parameters of cancellous bone (P < 0.05). CSII treatment significantly improved partial mesoscopic-macroscopic mechanical parameters and some cortical bone mineral composition parameters (P < 0.05). CONCLUSIONS: CSII treatment can significantly improve the nanoscopic-mesoscopic-apparent-macroscopic mechanical properties of the lumbar spine in T2D rats, as well as the bone structure and bone mineral composition of the lumbar vertebrae, but it will take longer treatment time to restore the normal level. In addition, T2D and CSII treatment affected bone mineral composition of cortical bone earlier than cancellous bone of lumbar spine in rat. Our study can provide evidence for clinical prevention and treatment of T2D-related bone diseases.

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats.

BACKGROUND: Verapamil was mainly used to treat hypertension, cardiovascular disease, inflammation and improve blood glucose in patients with diabetes, but its effects on bone mass, microstructure and mechanical properties were unclear. This study described the effects of verapamil on bone mass, microstructure, macro and nano mechanical properties in type 2 diabetic rats. METHODS: Rat models of type 2 diabetes were treated with verapamil at doses of 4, 12, 24 and 48 mg/kg/day by gavage respectively, twice a day. After 12 weeks, all rats were sacrificed under general anesthesia. Blood glucose, blood lipid, renal function and biochemical markers of bone metabolism were obtained by serum analysis, Micro-CT scanning was used to assess the microstructure parameters of cancellous bone of femoral head, three-point bending test was used to measure maximum load and elastic modulus of femoral shaft, and nano-indentation tests were used to measure indentation moduli and hardnesses of longitudinal cortical bone in femoral shaft, longitudinal and transverse cancellous bones in femoral head. RESULTS: Compared with T2DM group, transverse indentation moduli of cancellous bones in VER 24 group, longitudinal and transverse indentation moduli and hardnesses of cancellous bones in VER 48 group were significantly increased (p < 0.05). Furthermore, the effects of verapamil on blood glucoses, microstructures and mechanical properties in type 2 diabetic rats were dependent on drug dose. Starting from verapamil dose of 12 mg/kg/day, with dose increasing, the concentrations of P1NP, BMD, BV/TV, Tb. Th, Tb. N, maximum loads, elastic moduli, indentation moduli and hardnesses of femurs in rats in treatment group increased gradually, the concentrations of CTX-1 decreased gradually, but these parameters did not return to the level of the corresponding parameters of normal rats. Verapamil (48 mg/kg/day) had the best therapeutic effect. CONCLUSION: Verapamil treatment (24, 48 mg/kg/day) significantly affected nano mechanical properties of the femurs, and tended to improve bone microstructures and macro mechanical properties of the femurs, which provided guidance for the selection of verapamil dose in the treatment of type 2 diabetic patients.

Loss of NLRP3 Function Alleviates Murine Hepatic Graft-versus-Host Disease.

NLRP3 is associated with multiple risks in graft-versus-host disease, though unifying principles for these findings remain largely unknown. To explore the effects and mechanisms of the absence of NLRP3 function on hepatic graft-versus-host-disease, we established an allogeneic hematopoietic cell transplantation mice model by infusing bone marrow mononuclear cells and spleno-T cells of the BALB/c mouse into either NLRP3 knockout (NLRP3-/- ) or wild-type C57BL/6 mice. Elevated inflammatory cell infiltration, liver fibrosis, and secretions of alanine aminotransferase (ALT) and aspartate transaminase (AST), together with weight loss, were observed in C57BL/6 recipients after transplantation. However, moderate injury pathology was detected in the liver of NLRP3-/- recipients at day 14, which gradually improved over time. Likewise, proinflammatory cytokine IL-1ß, a downstream effecter of NLRP3 inflammasome activation, showed significantly lower expression (P < .05) in the liver of NLRP3-/- recipients relative to C57BL/6 recipients at day 7 and day 21. Moreover, compared with C57BL/6 recipients, the expression of both TNF-α and IL-1ß were decreased 3-fold and 4.7-fold, respectively, at day 21 in NLRP3-/- recipients. Interestingly, NLRP1a was expressed at a significantly reduced level in the liver of NLRP3-/- recipients (P < .001). Furthermore, systemic inflammation was analyzed by measuring the concentration of IL-1ß and adenosine triphosphate (ATP) in serum. The concentration of IL-1ß achieved a maximum at day 14, then decreased at day 21 and day 28 in NLRP3-/- recipients. In contrast, the concentration of IL-1ß in C57BL/6 recipients gradually increased from day 7 to day 28. ATP levels reduced from day 7 to day 28 in NLRP3-/- recipients, but were extremely high in C57BL/6 recipients from day 14 to day 28 (P < .01). The decreased levels of P2X7R were connected to less ATP in NLRP3-/- recipients at day 21 and day 28. In conclusion, NLRP3 knockout in recipients could significantly relieve liver injury after transplantation and block the NLRP3 inflammasome pathway, thus providing a promising strategy for the treatment of graft-versus-host disease prophylaxis.

Differential analysis of quantitative proteome and acetyl-proteome profiling between premenopausal and postmenopausal ovarian tissues.

BACKGROUND: Natural menopause is always accompanied by specific signs and symptoms, suggesting physiological changes in this peoriod. However, no systematic study has assessed the changes at molecular level in the ovaries during the menopausal transition so far. This study integrated quantitative proteome and acetyl-proteome to comprehensively uncover the changes of ovarian protein and protein-acetylation profiles in this transitional period. The findings would provide novel insights into the biology of menopause and help relieve and treat the associated signs and symptoms, further improving the women's health care. METHODS: Freshly thawed ovarian tissue samples obtained from premenopausal and postmenopausal women were assessed with Tandem Mass Tags for the quantitative analysis of the global profile and acetyl-proteomes by 2-dimensional separation and LC-MS/MS. RESULTS: Comprehensively, 4210 types of protein, with 3551 types quantifiable were detected. 3047 acetylated sites in 1583 types of protein with 2256 quantifiable in 1248 proteins were detected. By comparing the global and acetylated proteome profiles for postmenopausal women and premenopausal women, 151 types of proteins were found upregulated and 65 were downregulated, along with 23 acetylated sites upregulated and 220 sites downregulated. For Immune response, the complement and coagulation cascades plus the citrate cycle and cellular detoxification were found to be significantly enhanced, while the extracellular structure and matrix organization, ECM-receptor interactions plus the infections were markedly suppressed. In addition, the amino acids around the acetylated sites were enriched by motif analysis, which can help us uncover amino acid sequence and search for the specific target in the subsequent study. CONCLUSION: Global and acetylated proteome Profiles in ovary differ between the premenopausal and postmenopausal groups. These proteomic-level changes may offer some potential biological markers to identify the pathological changes in ovary and help relieve and treat the associated signs and symptoms, and ultimately improve women's health care.

Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer.

Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion. This phase 1 study evaluated the safety of p38 MAPK inhibitor LY3007113 in patients with advanced cancer to establish a recommended phase 2 dose. Methods In part A (dose escalation), LY3007113 was administered orally every 12 h (Q12H) at doses ranging from 20 mg to 200 mg daily on a 28-day cycle until the maximum tolerated dose (MTD) was reached. In part B (dose confirmation), patients received MTD. Safety, pharmacokinetics, pharmacodynamics, and tumor response data were evaluated. Results MTD was 30 mg Q12H. The most frequent treatment-related adverse events (>10%) were tremor, rash, stomatitis, increased blood creatine phosphokinase, and fatigue. Grade ≥ 3 treatment-related adverse events included upper gastrointestinal haemorrhage and increased hepatic enzyme, both occurring at 40 mg Q12H and considered dose-limiting toxicities. LY3007113 exhibited an approximately dose-proportional increase in exposure and time-independent pharmacokinetics after repeated dosing. Maximal inhibition (80%) of primary biomarker MAPK-activated protein kinase 2 in peripheral blood mononuclear cells was not reached, and sustained minimal inhibition (60%) was not maintained for 6 h after dosing to achieve a biologically effective dose (BED). The best overall response in part B was stable disease in 3 of 27 patients. Conclusions The recommended phase 2 dosage of LY3007113 was 30 mg Q12H. Three patients continued treatment after the first radiographic assessment, and the BED was not achieved. Further clinical development of this compound is not planned as toxicity precluded achieving a biologically effective dose.

Matrix-Infrared Spectra and Structures of HM-SiH3 (M = Ge, Sn, Pb, Sb, Bi, Te Atoms).

The reactions of Ge, Sn, Pb, Sb, Bi, and Te atoms with silane molecules were studied using matrix-isolation Fourier transform infrared spectroscopy and density functional theoretical (DFT) calculations. All metals generate the inserted complexes HM-SiH3, which were stabilized in an argon matrix, while H2M═SiH2 and H3M≡SiH were not observed. DFT and CCSD(T) calculations show the insertion complex HM-SiH3 is the most stable isomer with a near right angle H-M-Si moiety. However, silydene complexes H2M═SiH2 (M = C, Si) were calculated and identified as the most stable complexes with the lighter elements. The bonding difference is mainly due to relativistic effects, which is that for heavier metal atoms valence s and p orbitals have a lower tendency to form hybrid orbitals.

Double and Triple Si-H-M Bridge Bonds: Matrix Infrared Spectra and Theoretical Calculations for Reaction Products of Silane with Ti, Zr, and Hf Atoms.

Infrared spectra of matrix isolated dibridged Si(µ-H)2MH2 and tribridged Si(µ-H)3MH molecules (M = Zr and Hf) were observed following the laser-ablated metal atom reactions with SiH4 during condensation in excess argon and neon, but only the latter species was observed with titanium. Assignments of the major vibrational modes, which included terminal MH, MH2 and hydrogen bridge Si-H-M stretching modes, were confirmed by the appropriate SiD4 isotopic shifts and density functional vibrational frequency calculations (B3LYP and BPW91). The Si-H-M hydrogen bridge bond is calculated as weak covalent interaction and compared with the C-H···M agostic interaction in terms of electron localization function (ELF) analysis and noncovalent interaction index (NCI) calculations. Furthermore, the different products of Ti, Zr, and Hf reactions with SiH4 are discussed in detail.

Beneficial effects of creatine phosphate sodium for the treatment of Henoch-Schönlein purpura in patients with early renal damage detected using urinary kidney injury molecule-1 levels.

Henoch-Schönlein purpura (HSP) is a small-vessel disease in children that is often accompanied by kidney damage. Despite many efforts to improve the early assessment of renal injury in HSP patients, effective markers are still lacking. In recent years, the relationship between kidney injury molecule-1 (KIM-1) and tubulointerstitial injury has drawn much attention, especially regarding the diagnostic potential of serum and urinary KIM-1 levels. However, the diagnostic value of KIM-1 for detecting urinary kidney injury in HSP patients is still elusive. Furthermore, the treatment of Henoch-Schönlein purpura nephritis (HSPN) relies on the clinician's experience without performing renal biopsy, so it is important to find an effective biomarker and therapy. In the present study, we investigated the diagnostic value of urinary KIM-1 for early renal injury in HSP patients enrolled in a prospective, single-center study. Urinary KIM-1 levels were measured in 27 patients with HSP, 32 patients with HSPN (21 HSPN patients had undergone renal biopsy), and 16 healthy donors, as normal controls. The HSPN patients were randomly divided to receive either routine therapy (n = 13) or routine treatment combined with creatine phosphate sodium (CP) (n = 19). Urinary KIM-1 levels were significantly greater in the HSP and HSPN groups than those in the healthy control group (P < 0.01), and were significantly greater in the HSPN group than in the HSP group (P < 0.01). The urinary KIM-1 levels decreased significantly after 10-14 days of treatment with CP compared with conventional therapy (P < 0.05). CONCLUSION: Our results demonstrate the diagnostic value of KIM-1 and the therapeutic potential of CP for early renal damage in HSP patients. WHAT IS KNOWN: Urine kidney injury molecule-1 (KIM-1) is a sensitive biomarker for tubulointerstitial injury. Henoch-Schonlein purpura (HSP) usually presents with renal damage. WHAT IS NEW: Our results suggest that the urinary KIM-1 level is a sensitive and specific biomarker for the detection of early renal damage in HSP and may predict the severity of HSP and HSPN. The administration of creatine phosphate sodium (CP) may reduce urinary KIM-1 levels and thus correct the hypoxic condition of the kidney. Preconditioning with CP may also be a useful adjunct for preventing early renal damage in HSPN patients.

Open-label, single-arm, phase II study of enzastaurin in patients with follicular lymphoma.

This open-label, phase II study investigated whether enzastaurin, a protein kinase C-beta (PKCß) inhibitor, had activity in patients with grade 1 or 2 follicular lymphoma (FL). Adults with grade 1 or 2 FL who had no more than one prior treatment received oral enzastaurin continuously for up to 3 years. Of the 66 patients who received enzastaurin, 53 were evaluable for response. Overall response rate (ORR, primary efficacy endpoint) was 26.4% (3.8% complete response). Median (95% confidence interval) progression-free survival, time to response, and duration of response were 18.1 (11.5-28.3), 4.9 (2.8-8.1), and 22.3 (8.8-not applicable) months, respectively. In patients with tumour tissue available for biomarker analysis, ORRs in low versus high PKCß2 expression groups were 41.7% and 8.3%, respectively (P = 0.041). The most common, mainly low-grade drug-related adverse events were fatigue (25.8%), diarrhoea (25.8%), nausea (18.2%), and chromaturia (18.2%). Four (6.1%) patients had Grade 3 toxicity and one (1.5%) patient had Grade 4 toxicity. Enzastaurin demonstrated limited clinical activity in grade 1 or 2 FL. Patients with low PKCß2 expression in tumours had higher ORR than those with high PKCß2 expression. Enzastaurin was well tolerated with mostly grade 1 or 2 toxicities. Further studies may be warranted in select patient populations.

[Significance of serum cholesterol and fibrinogen in evaluating the risk of glomerulosclerosis in children with nephrotic syndrome].

OBJECTIVE: To investigate the significance of serum cholesterol and fibrinogen (Fib) in evaluating the risk of glomerulosclerosis in children with nephrotic syndrome. METHODS: Sixty-three children with primary nephrotic syndrome were divided into two groups according to their pathological types: minimal change glomerulopathy (MCG) (n=39) and focal segmental glomerulosclerosis (FSGS) groups (n=24). Serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and Fib and 24-hour urinary protein excretion were retrospectively analyzed. RESULTS: Serum levels of TC, non-HDL-C, and LDL-C were significantly higher in the FSGS group than in the MCG group (P<0.05), but there were no significant differences in HDL-C, Fib and 24-hour urinary protein excretion between the two groups (P>0.05). According to the results of logistic regression analysis, high levels of LDL-C, non-HDL-C and TC were risk factors for FSGS (P<0.05). In patients whose proteinuria did not disappear after taking enough glucocorticoid for 4 weeks, the level of non-HDL-C was significantly higher in the FSGS group than in the MCG group (P<0.05); there were no significant differences in TC, LDL-C, HDL-C, and Fib between the MCG and FSGS groups (P>0.05). CONCLUSIONS: Serum cholesterol, especially non-LDL-C, is of great significance in evaluating the risk of glomerulosclerosis in children with nephrotic syndrome. There is no sufficient evidence to support serum Fib as a marker for predicting glomerulosclerosis in these children.

Unveiling the detrimental vicious cycle linking skeletal muscle and COVID-19: A systematic review and meta-analysis.

OBJECTIVE: Skeletal muscle catabolism supports multiple organs and systems during severe trauma and infection, but its role in COVID-19 remains unclear. This study investigates the interactions between skeletal muscle and COVID-19. METHODS: The PubMed, EMbase, and The Cochrane Library databases were systematically searched from January 2020 to August 2023 for cohort studies focusing on the impact of skeletal muscle on COVID-19 prevalence and outcomes, and longitudinal studies examining skeletal muscle changes caused by COVID-19. Skeletal muscle quantity (SMQN) and quality (SMQL) were assessed separately. The random-effect model was predominantly utilized for statistical analysis. RESULTS: Seventy studies with moderate to high quality were included. Low SMQN/SMQL was associated with an increased risk of COVID-19 infection (OR = 1.62, p < 0.001). Both the low SMQN and SMQL predicted COVID-19-related mortality (OR = 1.53, p = 0.016; OR = 2.18, p = 0.001, respectively). Mortality risk decreased with increasing SMQN (OR = 0.979, p = 0.009) and SMQL (OR = 0.972, p = 0.034). Low SMQN and SMQL were also linked to the need for intensive care unit/mechanical ventilation, increased COVID-19 severity, and longer hospital stays. Significant skeletal muscle wasting, characterized by reduced volume and strength, was observed during COVID-19 infection and the pandemic. CONCLUSIONS: This study reveals a detrimental vicious circle between skeletal muscle and COVID-19. Effective management of skeletal muscle could be beneficial for treating COVID-19 infections and addressing the broader pandemic. These findings have important implications for the management of future virus pandemics. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023395476.

A randomized, double-blind, placebo-controlled, Phase II study with and without enzastaurin in combination with docetaxel-based chemotherapy in patients with castration-resistant metastatic prostate cancer.

PURPOSE: Enzastaurin is an oral serine/threonine kinase inhibitor that inhibits the beta isoform of protein kinase C and which may have therapeutic activity in prostate cancer. We explored the efficacy of docetaxel/prednisone with or without enzastaurin in patients with castration-resistant metastatic prostate cancer. METHODS: A nonrandomized safety cohort consisting of 14 patients was followed by a double-blind randomized Phase II trial. Patients received standard doses of docetaxel (75 mg/m(2)) with prednisone 10 mg daily with or without 500 mg/day of enzastaurin. RESULTS: There was no difference in the objective response rate between the enzastaurin and placebo arms (placebo: 7 [15.2 %]; enzastaurin: 6 [15.0 %]; P = 1.00). The median PFS was 229 days for patients in the enzastaurin arm versus 213 days for the placebo arm (P = 0.524). The 1-year overall survival rates were almost identical, with 76.7 % and 75.1 % in the enzastaurin and placebo arms, respectively. Therapy was well tolerated although the combination of enzastaurin and docetaxel was more myelosuppressive than with docetaxel alone. CONCLUSIONS: The clinical activity of docetaxel/prednisone plus enzastaurin cannot be distinguished from docetaxel/prednisone alone, given the limitations of a randomized Phase II design. Although the toxicity profile was favorable for the enzastaurin-containing regimen, there is no compelling rationale to move this combination forward for the treatment of castration-resistant metastatic prostate cancer.

Role of abnormal glycosylated IgA1 and interstitial transformation of glomerular endothelial cells in the development and progression of IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is a common primary renal disease in childhood. METHODS: Twenty blood samples and renal tissue from patients with IgAN, 20 blood samples from healthy children and 10 normal renal tissue were collected. Serum Gd-IgA1 and renal Gd-IgA1, CD31, α-SMA and vimentin were measured. RESULTS: The serum Gd-IgA1 concentration in the IgAN group was significantly higher. Gd-IgA1 was not expressed in normal kidneys, which was positive in the IgAN group. Gd-IgA1 levels in serum and renal tissue were not related. The expression of CD31 decreased significantly in IgAN group, while the expression of α-SMA and vimentin increased significantly. There was no significant correlation between the renal concentration of Gd-IgA1 and CD31, α-SMA and vimentin. CONCLUSION: The increased Gd-IgA1 in the serum and kidney may promote the pathogenesis of IgAN. The serum Gd-IgA1 cannot predict the extent of its deposition in the kidney. Endothelial mesenchymal transition (EndMT) may be involved in the pathogenesis of renal fibrosis in IgAN.

Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review.

BACKGROUND: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors. METHODS: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, and Cochrane Library up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness. RESULTS: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36 % ([95 % CI 15.27-32.53]). The generalized symptom (19.57 %, [95 % CI 9.85-31.52]) was reported most commonly, followed by respiratory (14.76 %, [95 % CI 7.22-24.27]), neurologic (13.51 %, [95 % CI 6.52-22.40]), and psychiatric (12.30 %, [95% CI 5.38-21.37]). Dyspnea (22.75 %, [95% CI 9.38-39.54]), fatigue (20.22 %, [95% CI 9.19-34.09]), and headache (15.88 %, [95 % CI 6.85-27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3-6, 6-12, and> 12 months were 26.41 % ([95 % CI 14.33-40.59]), 20.64 % ([95 % CI 17.06-24.46]), and 14.89 % ([95 % CI 6.09-26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors. CONCLUSIONS: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.

Improved color rendering of phosphor-converted white light-emitting diodes with dual-blue active layers and n-type AlGaN layer.

An InGaN/GaN blue light-emitting diode (LED) structure and an InGaN/GaN blue-violet LED structure were grown sequentially on the same sapphire substrate by metal-organic chemical vapor deposition. It was found that the insertion of an n-type AlGaN layer below the dual blue-emitting active layers showed better spectral stability at the different driving current relative to the traditional p-type AlGaN electron-blocking layer. In addition, color rendering index of a Y3Al5O12:Ce3+ phosphor-converted white LED based on a dual blue-emitting chip with n-type AlGaN reached 91 at 20 mA, and Commission Internationale de L'Eclairage coordinates almost remained at the same point from 5 to 60 mA.

[A clinico-pathological comparison between Henoch-Schonlein purpura nephritis and IgA nephropathy in children].

OBJECTIVE: To study the difference in clinico-pathological features between IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN) in children. METHODS: The medical data of 103 children with HSPN and 61 children with IgAN were retrospectively studied. RESULTS: There were no significant differences in age, sex and disease course between the HSPN and IgAN groups (P>0.05). Clinical classification demonstrated that more severe conditions were found in the IgAN group than in the HSPN group and gross hematuria was more common in the IgAN group (P<0.05). Serum creatinine and cholesterol levels were higher in the IgAN group than in the HSPN group (P<0.05). Fibrinogen-related antigen deposition was more common in the HSPN group, while complement 3(C3) deposition was more common in the IgAN group. Interstitial fibrosis, tubular casts and tubular inflammatory infiltration were also more common in the IgAN group (P<0.05). CONCLUSIONS: Significant clinico-pathological differences can be found between HSPN and IgAN in children, and these differences do not support a one disease entity hypothesis.