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.

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.

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.

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.

Obstacles to Exercising Reproductive Rights for Single Women in China and Legal Recommendations.

Purpose: Reproductive rights represent an intrinsic and pivotal human entitlement, encompassing legal protection for procreation. Essential to this framework is the recognition that single women equally deserve reproductive rights. Although Chinese legislation refrains from overtly disallowing reproductive rights for single women, the interplay of conventional marriage norms and family planning policies has inadvertently tied these rights to marital status, consequently constraining single women's ability to assert them. The establishment of a robust legal structure to ensure reproductive rights for single women would profoundly contribute to advancing a harmonious evolution of China's population dynamics. Patients and Methods: We employ meticulous textual scrutiny to analyze comprehensively the stipulations concerning women's reproductive liberties within the framework of Chinese jurisprudence. Furthermore, we engage in empirical inquiry to enumerate and elucidate the multifarious constraints placed upon the reproductive freedoms of unmarried women in the Chinese context. This endeavor entails a detailed exposition and incisive examination of China's limitations imposed upon the reproductive rights of single women, encompassing both legal strictures and policy dimensions. Results: The absence of legal endorsement and safeguarding has given rise to substantial impediments to the exercise of reproductive rights among single women in China. Not only do endeavors to assert reproductive rights on behalf of single women encounter intricate challenges in judicial implementation, but they also encounter manifold barriers within national policies. This predicament not only subjects single women to considerable psychological strain but also contradicts the overarching objective of achieving a harmonized population development trajectory in China. Conclusion: China should expedite the development of a legal framework for protecting reproductive rights that includes provisions for supporting single women to have children. This legal apparatus should efficaciously enshrine and shield the reproductive rights of single women, thus playing a pivotal role in advancing a more equitable and well-balanced trajectory of population development.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis: a nationwide retrospective study in China.

BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).

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.

Steroid-resistant nephrotic syndrome caused by nuclear pore gene NUP133 variation.

Partially enlarged structure of NUP133: wild-type (upper) and mutant p.Lys966Asn (lower).

Growth hormone treatment in pre-pubertal short Chinese children with chronic kidney disease prior to transplantation.

BACKGROUND: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear. METHODS: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks. RESULTS: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention. CONCLUSIONS: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety. IMPACT: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.

Effects of glucocorticoids on leukocytes: Genomic and non-genomic mechanisms.

Glucocorticoids (GCs) have been widely used as immunosuppressants and anti-inflammatory agents to treat a variety of autoimmune and inflammatory diseases, and they fully exert their anti-inflammatory and immune-regulating effects in the body. The effect of GCs on white blood cells is an important part of their action. GCs can cause changes in peripheral blood white blood cell counts by regulating the proliferation, differentiation, and apoptosis of white blood cells. Although the total number of white blood cells, neutrophil counts, lymphocytes, and eosinophils increases, the counts of basic granulocytes and macrophages decreases. In addition, GCs can regulate the activation and secretion of white blood cells, inhibit the secretion of a variety of pro-inflammatory cytokines, the expression of chemokines, and promote the production of anti-inflammatory cytokines. For patients on GC therapy, the effects of GCs on leukocytes were similar to the changes in peripheral blood caused by bacterial infections. Thus, we suggest that clinicians should be more cautious in assessing the presence of infection in children with long-term use of GCs and avoid overuse of antibiotics in the presence of elevated leukocytes. GCs work through genomic and non-genomic mechanisms in the human body, which are mediated by GC receptors. In recent years, studies have not fully clarified the mechanism of GCs, and further research on these mechanisms will help to develop new therapeutic strategies.

Novel Loss-of-Function Mutations in NPR2 Cause Acromesomelic Dysplasia, Maroteaux Type.

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare skeletal dysplasia characterized by severe disproportionate short stature, short hands and feet, normal intelligence, and facial dysmorphism. Homozygous or compound heterozygous mutations in the natriuretic peptide receptor 2 (NPR2) gene produce growth-restricted phenotypes. The current study was designed to identify and characterize NPR2 loss-of-function mutations in patients with AMDM and to explore therapeutic responses to recombinant growth hormone (rhGH). NPR2 was sequenced in two Chinese patients with AMDM via next generation sequencing, and in silico structural analysis or transcript analysis of two novel variants was performed to examine putative protein changes. rhGH treatment was started for patient 1. Three NPR2 mutations were identified in two unrelated cases: two compound heterozygous mutations c.1112G>A p.(Arg371Gln) and c.2887+2T>C in patient 1 and a homozygous mutation c.329G>A p.(Arg110His) in patient 2, yielding distinct phenotypes. RNA extracted from peripheral blood cells of patient 1 showed alternatively spliced transcripts not present in control cells. Homology modeling analyses suggested that the c.1112G>A p.(Arg371Gln) mutation disrupted the binding of NPR-B homodimer to its ligand (C-type natriuretic peptide) in the extracellular domain as a result of global allosteric effects on homodimer formation. Thus, c.2887+2T>C and c.1112G>A p.(Arg371Gln) in NPR2 were loss-of-function mutations. Furthermore, rhGH therapy in patient 1 increased the patient's height by 0.6SDS over 15 months without adversely affecting the trunk-leg proportion. The short-term growth-promoting effect was equivalent to that reported for idiopathic short stature. Overall, our findings broadened the genotypic spectrum of NPR2 mutations in individuals with AMDM and provided insights into the efficacy of rhGH in these patients.

Impact of body mass index on primary immunoglobulin A nephropathy prognosis: a systematic review and meta-analysis.

PURPOSE: The impacts of body mass index (BMI) on the prognosis of primary IgA nephropathy (IgAN) remain controversial. This systematic review and meta-analysis aimed to solve these issues. METHODS: We searched the PubMed, EMBASE, and Cochrane Library to screen articles investigating the BMI and primary IgAN. BMI was classified according to the World Health Organization as high (≥ 25.0 kg/m2) and low (< 25.0 kg/m2). The baseline renal indexes and the incidences of adverse renal outcomes were focused on. RESULTS: Six studies with a total of 1723 patients were included in this study. High BMI was demonstrated to be associated with increased baseline levels of serum creatinine (weighted mean difference (WMD) 9.54, 95% confidence interval (CI) 0.63-18.45), blood uric acid (WMD 19.85, 95% CI 10.11-29.59) and urine protein (WMD 0.37, 95% CI 0.21-0.53). Patients with high BMI also showed compromised eGFR at diagnosis (WMD - 8.39, 95% CI - 11.62 to - 5.16) with a higher incidence rate of hypertension (odds ratios (OR) 2.59, 95% CI 1.44-4.66) and higher global optical scores (WMD 1.22, 95% CI 0.70-1.74). Regarding the prognosis, high BMI was significantly associated with the incidence of adverse renal outcomes (OR 2.43, 95% CI 1.66-3.55, P < 0.001) and deteriorated eGFR at the last follow-up (WMD - 11.10, 95% CI - 16.96 to - 5.25, P < 0.001), with non-significantly poorer renal disease-free survival (hazard ratio 1.79, 95% CI 0.58-5.50, P = 0.31). CONCLUSION: High BMI was associated with severe onset and poor prognosis of primary IgAN. The management of BMI could be a novel method to promote the therapeutic outcomes of primary IgAN.

The important roles and molecular mechanisms of annexin A2 autoantibody in children with nephrotic syndrome.

BACKGROUND: In recent years, B-cell dysfunction has been found to play an important role in the pathogenesis of primary nephrotic syndrome (PNS). B cells play a pathogenic role by secreting antibodies against their target antigens after transforming into plasma cells. Therefore, this study aimed to screen the autoantibodies that cause PNS and explore their pathogenic mechanisms. METHODS: Western blotting and mass spectrometry were employed to screen and identify autoantibodies against podocytes in children with PNS. Both in vivo and in vitro experiments were used to study the pathogenic mechanism of PNS. The results were confirmed in a large multicenter clinical study in children. RESULTS: Annexin A2 autoantibody was highly expressed in children with PNS with a pathological type of minimal change disease (MCD) or focal segmental glomerulosclerosis without genetic factors. The mouse model showed that anti-Annexin A2 antibody could induce proteinuria in vivo. Mechanistically, the effect of Annexin A2 antibody on the Rho signaling pathway was realized through promoting the phosphorylation of Annexin A2 at Tyr24 on podocytes by reducing its binding to PTP1B, which led to the cytoskeletal rearrangement and damage of podocytes, eventually causing proteinuria and PNS. CONCLUSIONS: Annexin A2 autoantibody may be responsible for some cases of PNS with MCD/FSGS in children.

Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis: a prospective, comparative study.

INTRODUCTION: To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis (PMNE), a new modified 3-day weekend frequency-volume chart (FVC) was designed, and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society (ICCS) recommended voiding diary. METHODS: A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary. The primary outcome measure was the compliance, assessed by comparing the completing index and the quality score of diaries between two groups. The secondary outcome measure was the validity, evaluated by comparing the constituent of subtypes, micturition parameters and response rate to desmopressin. RESULTS: Among the 1200 participants enrolled in the study, 447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary. The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group. In addition, there was no significant difference between these two groups in the subtype classification, or in the response rate to desmopressin. CONCLUSIONS: The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

The role of miR-199b-3p in regulating Nrf2 pathway by dihydromyricetin to alleviate septic acute kidney injury.

The pathophysiology of septic acute kidney injury (AKI) is very complex and the fatality is high. Nrf2 is crucial for septic AKI, and dihydromyricetin (DMY) has a protective effect on LPS-induced AKI. We aimed to explore whether DMY could affect Nrf2 pathway by regulating miR-199b-3p and played a protective role in septic AKI. The mouse model was induced by cecal ligation and puncture (CLP) and the cell model was stimulated by LPS. Enzyme-linked immunosorbent assay was conducted to examine MDA, SOD, LDH, GSH, TNF-α, kidney injury molecule 1 (KIM-1), and IL-6 levels. The pathological changes were observed by hematoxylin-eosin staining. The targeted relationship between miR-199b-3p and Nrf2 was verified by a dual-luciferase reporter assay. Levels of SOD, GSH, NQO-1, Nrf2, and HO-1 were decreased, MDA, LDH, TNF-α, IL-6, and KIM-1, and miR-199b-3p were increased in the CLP group and LPS-induced HK-2 cells, while the effect was reversed after DMY treatment. There existed renal tubule cell edema and necrosis, inflammatory cell infiltration in the CLP group, the situation was partially improved by DMY. MiR-199b-3p bound to Nrf2. Nrf2 levels were increased, TNF-α, IL-6, and KIM-1 were decreased after transfected with miR-199b-3p inhibitor, these effects were reversed when co-transfected with si-Nrf2. TNF-α, IL-6, KIM-1, and miR-199b-3p levels were increased; Nrf2, NQO-1, and HO-1 levels were decreased in the LPS + DMY + mimics-miR group. MiR-199b-3p was increased in septic AKI models, DMY might alleviate septic AKI by regulating miR-199b-3p to affect the Nrf2 pathway.

LncRNA PVT1 Suppresses the Progression of Renal Fibrosis via Inactivation of TGF-ß Signaling Pathway.

BACKGROUND: Renal fibrosis is a frequent pathway leading to end-stage kidney dysfunction. In addition, renal fibrosis is the ultimate manifestation of chronic kidney diseases (CKD). Long noncoding RNAs (lncRNAs) are known to be involved in occurrence of renal fibrosis, and lncRNA plasmacytoma variant translocation 1 (PVT1) has been reported to act as a key biomarker in renal diseases. However, the role of PVT1 in renal fibrosis remains unclear. MATERIALS AND METHODS: HK-2 cells were treated with TGF-ß1 to mimic renal fibrosis in vitro. Gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of creatinine (CR) and blood urea nitrogen (BUN) in serum of mice. Additionally, unilateral ureteral obstruction (UUO)-induced renal fibrosis mice model was established to investigate the effect of PVT1 on renal fibrosis in vivo. RESULTS: PVT1 was upregulated in TGF-ß1-treated HK-2 cells. In addition, TGF-ß1-induced upregulation of α-SMA and fibronectin in HK-2 cells was significantly reversed by PVT1 knockdown. Meanwhile, PVT1 bound to miR-181a-5p in HK-2 cells. Moreover, miR-181a-5p directly targeted TGF-ßR1. Furthermore, miR-181a-5p antagonist could significantly reverse the anti-fibrotic effect of PVT1 knockdown. Besides, knockdown of PVT1 notably attenuated the symptom of renal fibrosis in vivo. CONCLUSION: Knockdown of PVT1 significantly inhibited the progression of renal fibrosis in vitro and in vivo. Thus, PVT1 may serve as a potential target for the treatment of renal fibrosis.

Analysis of Occupational Stress and Its Relationship with Secretory Immunoglobulin A in the Xinjiang Plateau Young Military Recruits.

BACKGROUND: With the continuous improvement of the modernization of the Chinese military and the major adjustments made by the state to the recruitment policy, the newly recruited military undergone multiple pressures such as targeted high-intensity military training and environmental changes. The mental health of military has become a crucial factor of improving the fighting capacity effectiveness of the troops. OBJECTIVES: To explore occupational stress of young recruits in the Xinjiang plateau environment during their basic military training period and analyze the relationship between occupational stress and secretory immunoglobulin A (sIgA) levels. METHODS: Using multistage stratified cluster random sampling, 625 recruits stationed at Xinjiang plateau command in 2014 were enrolled as subjects. Occupational stress was assessed by the Occupational Stress Inventory Revised Edition (OSI-R). sIgA in saliva was quantified by enzyme-linked immunosorbent assay. The resulting data were analyzed using descriptive statistics, nonparametric tests, and correlation analysis. RESULTS: Based on demographic characteristics, occupational stress was higher in the urban group than the rural group, coping ability for stress was greater in individuals who were students before joining the army than nonstudents, occupational stress was higher in smokers than nonsmokers, and coping ability for stress was higher in nonsmokers than in smokers (all P < 0.05). Being an only child, educational level and age were not significantly related to occupational stress scores (P > 0.05). Salivary sIgA level was higher in the high occupational stress group than in the low stress group (P < 0.01). Salivary sIgA was positively correlated with scores on the occupational role and personal strain questionnaires (r s = 0.229, r s = 0.268, P < 0.01). CONCLUSION: Demographic characteristics influenced occupational stress among young recruits in cold and high-altitude area. Further, there were some relationships between occupational stress and salivary sIgA in young military recruits.

Long noncoding RNA MALAT1 promotes the stemness of esophageal squamous cell carcinoma by enhancing YAP transcriptional activity.

The tumor promoting roles of long noncoding RNA (lncRNA) MALAT1 have been revealed in various cancers; however, its roles in esophageal squamous cell carcinoma (ESCC) have not previously been disclosed. In this study, we found that MALAT1 expression was remarkably increased in ESCC cells compared to normal human esophageal epithelial cells. In addition, knockdown of MALAT1 attenuated the stemness of ESCC cells, as evidenced by a decrease in spheroid formation capacity, stemness marker expression and aldehyde dehydrogenase 1 activity. Moreover, MALAT1 knockdown decreased the migration ability of ESCC cells. Notably, knockdown of MALAT1 enhanced the radiosensitivity and chemosensitivity of ESCC cells. We also established that MALAT1 binds directly to Yes-associated protein (YAP), thereby enhancing YAP protein expression and increasing YAP transcriptional activity. Overexpression of YAP partially rescued the effect of MALAT1 knockdown on stemness and radiosensitivity of ESCC cells. Overall, this study has identified that a novel MALAT1-YAP axis promotes the stemness of ESCC cells, and thus could be a potential target for treatment of ESCC.

[Clinical effect of tacrolimus combined with glucocorticoid in the treatment of IgA nephropathy in children].

OBJECTIVE: To study the clinical effect and safety of tacrolimus (TAC) combined with glucocorticoid (GC) versus mycophenolate mofetil (MMF) combined with GC in the treatment of primary IgA nephropathy (IgAN) in children. METHODS: A retrospective analysis was performed for the clinical data of children with primary IgAN confirmed by renal pathology between January 2012 and December 2017. These children were divided into TAC group and MMF group according to the treatment regimen. Their clinical data before treatment and at 1, 3, and 6 months of treatment were collected, and the remission status of IgAN and adverse reactions were compared between the two groups. RESULTS: A total of 43 children who met the inclusion criteria were enrolled, with 15 children in the TAC group and 28 children in the MMF group. At 1 month of treatment, there was no significant difference in the remission status between the two groups (P>0.05). At 3 and 6 months of treatment, the TAC group had a significantly better remission status than the MMF group (P<0.05). At 1 month of treatment, the TAC group had higher serum albumin levels than the MMF group (P<0.05). Both groups had a significant increase in serum albumin levels at each time point after treatment (P<0.0083) and a significant increase in the glomerular filtration rate (GFR) at 3 and 6 months of treatment (P<0.0083). There was no significant difference in the overall incidence rate of adverse reactions between the two groups (P>0.05), but fungal infection was observed in one child from the TAC group. CONCLUSIONS: TAC combined with GC can effectively reduce urinary protein in children with primary IgAN, and it has a better short-term clinical effect than MMF combined with GC, with good safety.

Microglia activation in the offspring of prenatal Poly I: C exposed rats: a PET imaging and immunohistochemistry study.

BACKGROUND: The well-known 'pyrotherapy' of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinflammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic-polyribocytidilicacid (Poly I:C) during pregnancy using 11C-PK11195 positron emission tomography (PET) and immunohistochemistry. OBJECTIVE: The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats. METHODS: Offspring of Poly I:C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition (PPI) and latent inhibition (LI) test (including active avoidance conditioning task and passive avoidance conditioning task). Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation. RESULTS: The treatment group showed hyperlocomotion and deficits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex (t=-3.990, p=0.003) and hippocampus (t=-4.462, p=0.001). The number of activated microglia cells was significantly higher in the treatment group than in the control group (hippocampus: t=8.204, p<0.001; prefrontal: t=6.995, p<0.001). Within the treatment group, there were significant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry. CONCLUSIONS: The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.