OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

【Objective】 To explore the clinical characteristics and risk factors of renal function deterioration in children with renal dysplasia and chronic kidney disease (CKD), so as to provide a basis for the diagnosis, treatment, and management. 【Methods】 The clinical data of children with renal dysplasia complicated with CKD treated in the Children’s Hospital of Chongqing Medical University during 2012 and 2022 were retrospectively analyzed, including the gender, age of diagnosis, growth index, concomitant malformation and complications. According to the diagnostic criteria and staging standard of KDIGO2020 guidelines, patients with disease deteriorated to CKD stage 4-5 were enrolled into the regression group. Factors affecting the deterioration of renal function were determined with Cox regression analysis. 【Results】 A total of 122 children were involved, including 66 (54.1%) with CKD stag 4-5. There were more boys than girls. Bilateral and unilateral renal dysplasia occurred in 88 (72.13%) and 34 (27.87%) cases, respectively, and 64 (52.46%) cases were complicated with other urinary diseases. There were significant differences in weight, height and body mass index (BMI) among patients with CKD stage 1-5 (P<0.01). The age of onset of CKD <10 years, BMI lower than the 3rd percentile of the same sex and age, bilateral renal dysplasia, and one or more complications of congenital renal and urinary tract abnormalities (CAKUT) were the risk factors of deterioration of renal function (P<0.05). 【Conclusion】 Renal dysplasia complicated with CKD are more common in boys, with high incidence of bilateral renal dysplasia. Bilateral renal dysplasia, age of onset of CKD <10 years, BMI lower than 3% and complications are important influencing factors of renal dysplasia in children with CKD.

The synchronous abnormal discharge of neurons leads to epileptic seizures.However, in addition to neurons, microglia, as the main immune cells in the brain, plays an important role in the development and maintenance of neural circuits.Microglia is involved in early epileptic seizures, which can be mediated by increasing inflammatory cytokines and chemokines.Microglia can regulate the abnormal neurogenesis after epileptic seizures, promote the death of neurons after seizures, and cause neurodegeneration.Moreover, it can also affect synaptic pruning after seizures, eliminate synapses by phagocytosis or stripping, destroy the balance between synaptic excitation and inhibition, and aggravate seizures.Microglia plays an important role in the development of epilepsy.However, whether microglia participates in the occurrence of epilepsy still needs to be further studied.

Inherited neurotransmitter disorders are a group of rare nervous system diseases frequently diagnosed in children.The disorders are caused by biosynthesis, breakdown or transport detects of neurotransmitters or cofactors essential in their biosynthesis.They can be classified as primary and secondary disorders.The clinical phenotypes of primary inherited neurotransmitter disorders include developmental delay, dyskinesia, schizophrenia, and epilepsy.Among them, epilepsy is the main clinical phenotype.Gamma-aminobutyric acid, glutamate, acetylcholine, biogenic amine and other neurotransmitters are involved in the epileptogenesis.The epilepsy related to primary inherited neurotransmitter disorders has diverse phenotypes, from mild seizures to severe early onset epileptic encephalopathy.An inherited neurotransmitter disorder should be suspected in children with epilepsy if the following features are present: (1) early onset epileptic encephalopathies associated with developmental impairment, autonomic dysfunctions or movement disorders; (2) frequent occurrence of such peculiar electroencephalogram patterns as burst suppression, hypsarrhythmia, and diffused/focal/multifocal electroencephalogram abnormalities; (3) neuroradiological signs of metabolic intoxication; (4) detection of specific cerebrospinal fluid biomarkers.Early identification, diagnosis and treatment is of great significance in reducing the incidence, lowering the mortality rate, and improving the prognosis of patients with epilepsy related to primary inherited neurotransmitter disorders.

This commentary was based on the paper "Calorie Restriction with or without Time-Restricted Eating in Weight Loss" (TREATY trial) published recently in N Engl J Med, with the aim to introduce the study design of TREATY trial and discuss the main findings along with its clinical applicability. This trial offers additional evidence on the time-restricted eating and provides insights for future research.

Background::Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods::Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results::The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) ( χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2 = 6.95, P = 0.008), BDG ( χ2 = 10.43, P = 0.001), and fungal culture ( χ2 = 12.70, P < 0.001). Conclusions::Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

Objective:To find out predictors of the testicular ischemia caused by incarcerated inguinal hernia and evaluate the ischemic injury of the testis more accurately, which can indicate testicle exploration in time or prevent unnecessary testicle exploration.Methods:Pediatric patients (median: 9 months) undergoing operation of unilateral incarcerated inguinal hernia and ipsilateral testicular exploration from 1 Jul. 2013 to 30 Jun. 2019 were retrospectively investigated. Age at surgery, incarcerate duration, degree of intestinal and testicular injury, times of manual reduction and preoperative ultrasound data were collected. Statistical analysis was performed by SAS 9.4 (Copyright ? 2016 SAS Institute Inc.Cary, NC, USA) .Results:460 patients (median: 9 months) , of which 57 (12.39%) (median: 1.4 months, interquartile range 0.8-10.7 months) had severe testicular injury, and their average incarceration time was (23.9±9.3) h. Univariate logistic regression revealed that increased times of manual reduction, ultrasound scores, incarcerate duration and degree of intestinal injury were positively correlated with the degree of testicular ischemia, while age at surgery was negatively correlated with the degree of testicular ischemia ( P<0.05) . A model for calculating the probability of severe testicular ischemia injury was established: P= through multivariate analysis with backward stepwise logistic regression and 10-fold cross-validation was used for preliminary verification of the model. Conclusion:This study provides a relative reliable model to predict the risk of irreversible testicular ischemia due to incarcerated inguinal hernia using readily available clinical characteristics in young pediatrics with testicular ischemia.

Objective:To discuss the diagnosis and treatment of ectopic ureter company with the bladder neck and urethral maldevelopment in children.Methods:The clinical data of the 6 patients admitted to Children’s Hospital affiliated to Chongqing Medical University from September 1993 to April 2019 diagnosed as ectopic ureter company with the bladder neck and urethral maldevelopment were retrospectively reviewed. The 6 children were girls and the median age was 7 years old , ranged from 2 to 15 years old. All children had ectopic ureter, including 3 in left-sided, 1 in right-sided, and 2 in bilateral-sided. Five children presented the intermittent dribbling incontinence and one child presented the continuously incontinence without normal voiding. Through ultrasound, IVP, MRI, cystoscopy and retrograde urography, seven ureters were found ectopic position, including bladder neck in 4 cases, two ureters inserted in the vagina in 2 cases. There were two cases with duplex kidney and 4 cases with renal dysplasia. Preoperative cystoscopy revealed wide and short urethra in 1 case, wide bladder neck combined with wide and short urethra in 4 cases. The surgery type included nephrectomy in cases 1-3, bilateral ureter reimplantation in case 4 who had the bilateral ectopic ureter , bilateral ureter reimplantation and bladder neck reconstruction at the same time in case 5. Nephrectomy associated with bladder neck and urethral reconstruction in case 6.Results:Five patients were followed-up and one patient was lost to follow-up after the first operation. Mean follow-up was 41.2 months (ranging 2 to 84 months). Four patients with bladder neck and maldevelopment that were not solved intraoperatively got reoperations due to incontinence without remission. Case 1, who underwent urethral reconstruction and extension, and urinary incontinence was partially relieved. Case 2 was found to have wide bladder neck deformity, and then retrospectively got bladder neck reconstruction and urethrovaginal fistula repair in 3 years and 5 years later. The urinary incontinence was completely relieved. The ureteral stump of case 3 was resected 2 years after operation due to recurrent urinary tract infection, and then got twice bladder neck and urethral reconstruction in 3 years and 6 years later of nephrectomy. His incontinence was partially relieved. The case 4 got bladder neck and urethral reconstruction in one year after bilateral ureter reimplantation, and incontinence was partially relieved too. Among the two patients underwent combined surgery, the case 5, who got bilateral ureteral bladder replantation combined with bladder neck reconstruction, were lost to follow-up after surgery. The case 6 got dysplasia nephrectomy combined with bladder neck reconstruction and urethroplasty were completely relieved of urinary incontinence.Conclusions:Bladder neck and urethra maldevelopment is one of the main causes of urinary incontinence after surgery in children with ectopic ureter. The diagnosis mainly relies on cystoscopy. The treatment mainly relies on surgery. Bladder neck and urethral reconstruction is expected to be available. If the operative conditions permit, synchronous surgical treatment of ectopic ureter and bladder neck and urethral maldevelopment will get a better prognosis than staging surgery.

We explored the improved method to prepare decellularized kidney scaffold and provide experimental basis for kidney tissue engineering and renal pathology and toxicology in vitro research. We perfused rat kidneys with PBS (group control) and prepared the decellularized kidney scaffolds with sodium dodecyl sulfate (SDS) (group S), Triton X-100 combined with SDS (group TS), and Triton X-100 combined with SDS after repeated freezing and thawing (group FTS) in different flow velocity. Meanwhile we measured their fluid distributions and vascular resistance. We examined the degree of decellularization of acellular scaffolds by HE, DAPI staining and DNA quantification. We examined the retention of main composition and structural integrity of decellularized scaffolds by Masson, PAS and immunohistochemical staining. We also detected the ultrastructure, cytotoxicity and the level of growth factor of the scaffolds by scanning electron microscope, MTT and ELISA, respectively. The results showed that the time of decellularization in group FTS was less than that in group S and TS. The vascular resistance of scaffolds decellularized at 10 mL/min flow velocity was lower. The fluid distribution in groups S, TS and FTS was different from that in control group. No residual cell was detected by HE and DAPI staining. DNA content was less than 50 ng/mg. Masson, PAS and immunohistochemical staining results showed that there was extracellular collagen, polysaccharide, type I collagen, type IV collagen, fibronectin and laminin in the decellularized scaffolds, and the scanning electron microscope result showed the scaffolds had the honeycomb structure. The cytotoxicity level of decellularized scaffolds was between grade 0 to 1. The level of VEGF, EGF, IGF-1 and PDGF-BB in group FTS were significantly higher than those in group S and TS. In concluding, combining freeze-thawing with perfusion can produce more ideal and effective whole organ decellularized scaffold of rat kidney, and make a foundation for the study of kidney tissue engineering and in vitro pathology and toxicology of kidney.
Animals ; Collagen ; Extracellular Matrix ; Freezing ; Kidney ; Perfusion ; Rats ; Tissue Engineering ; Tissue Scaffolds

OBJECTIVE: To investigate the transcriptome profile of genital tubercles (GTs) in male SD rats and explore the mechanism of hypospadias induced by Di (2-ethylhexyl) phthalate (DEHP). METHODS: Forty time-pregnant SD rats were randomly divided into 4 equal groups, namely GD16 group and GD19 group (in which the male GTs were collected on gestation day[GD]16 and GD19 for RNA-seq, respectively), control group and DEHP exposure group (with administration of oil and 750 mg/kg DEHP by gavage from GD12 to GD19, respectively).In the control and DEHP exposure groups, the GTs were collected from the male fetuses on GD19.5, and scanning electron microscopy and HE staining were used to observe the morphological changes.The differentially expressed genes (DEGs) in the GTs were screened using lllumina HiSeq 2000 followed by GO and KEGG enrichment analyses to characterize the transcriptome profile.Immunofluorescence assay was performed to verify the DEGs (Mafb) identified by RNA-seq results.Immunofluorescence assay and Western blotting were used to examine the expression levels of Mafb in the penile tissue. RESULTS: A total of 1360 DEGs were detected in the GTs between GD16 group and GD19 group by RNA-seq.Among these genes, 797 were up-regulated and 563 were down-regulated.These DEGs were mainly enriched in the cell adhesion plaque signaling pathway, axon guidance signaling pathway, and extracellular matrix receptor signaling pathway.Compared with that in GD16 group, Mafb was significantly up-regulated in GD19 group, which was consistent with the sequencing results.Mafb and β-catenin were significantly down-regulated in DEHP-exposed group compared with the control group ( < 0.01). CONCLUSIONS Mafb expression increases progressively with the development of GTs in male SD rats.DEHP exposure causes significant down-regulation of Mafb and β-catenin, suggesting that β-catenin signaling pathway that affects Mafb is related to DEHP-induced hypospadias in SD rats.
Animals ; Diethylhexyl Phthalate ; Female ; Gene Expression Profiling ; Humans ; Hypospadias ; MafB Transcription Factor ; Male ; Oncogene Proteins ; Phthalic Acids ; Pregnancy ; Rats ; Rats, Sprague-Dawley