Establishment and validation of a nomogram for predicting overall survival of upper-tract urothelial carcinoma with bone metastasis: a population-based study.

BACKGROUND: Bone metastasis (BM) carries a poor prognosis for patients with upper-tract urothelial carcinoma (UTUC). This study aims to identify survival predictors and develop a prognostic nomogram for overall survival (OS) in UTUC patients with BM. METHODS: The Surveillance, Epidemiology, and End Results database was used to select patients with UTUC between 2010 and 2019. The chi-square test was used to assess the baseline differences between the groups. Kaplan-Meier analysis was employed to assess OS. Univariate and multivariate analyses were conducted to identify prognostic factors for nomogram establishment. An independent cohort was used for external validation of the nomogram. The discrimination and calibration of the nomogram were evaluated using concordance index (C-index), area under receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). All statistical analyses were performed using SPSS 23.0 and R software 4.2.2. RESULTS: The mean OS for UTUC patients with BM was 10 months (95% CI: 8.17 to 11.84), with 6-month OS, 1-year OS, and 3-year OS rates of 41%, 21%, and 3%, respectively. Multi-organ metastases (HR = 2.21, 95% CI: 1.66 to 2.95, P < 0.001), surgery (HR = 0.72, 95% CI: 0.56 to 0.91, P = 0.007), and chemotherapy (HR = 0.37, 95% CI: 0.3 to 0.46, P < 0.001) were identified as independent prognostic factors. The C-index was 0.725 for the training cohort and 0.854 for the validation cohort, and all AUC values were > 0.679. The calibration curve and DCA curve showed the accuracy and practicality of the nomogram. CONCLUSIONS: The OS of UTUC patients with BM was poor. Multi-organ metastases was a risk factor for OS, while surgery and chemotherapy were protective factors. Our nomogram was developed and validated to assist clinicians in evaluating the OS of UTUC patients with BM.

Perfluorooctanoic acid inhibits androgen biosynthesis in rat immature Leydig cells.

Perfluorooctanoic acid (PFOA) is a commonly used short-chain synthetic perfluoroalkyl agent. Immature Leydig cells (ILCs) are localized in the testis and responsible for androgen biosynthesis and metabolism. Although PFOA shows toxicity in the reproductive system, it is not clear if it disrupts the function of ILCs. In the present study, primary ILCs were isolated from 35-day-old rats and exposed to a range of PFOA concentrations (0, 0.01, 0.1, or 1 µM). It was determined that 0.1 or 1 µM PFOA reduced total androgen biosynthesis in ILCs. Specifically, 22R-hydroxycholesterol (22R), and pregnenolone (P5) mediated androgen biosynthesis were reduced by 0.1 µM PFOA. PFOA also selectively downregulated mRNA and protein expressions of steroidogenic enzymes including LHCGR, CYP11A1, 3ß-HSD1, and NR5A1 at 0.01, 0.1, or 1 µM. Further analysis revealed that 0.1 µM PFOA inhibited CYP11A1 and 3ß-HSD1 enzyme activities. However, PFOA did not significantly affect androgen metabolism and turnover under any of the conditions tested. And PFOA gavaging to 35-day-old rats at 5 or 10 mg/kg for 7 or 14 days also reduced serum androgen levels secreted by ILCs. Moreover, PFOA gavaging also downregulated the mRNA and protein expression levels of LHCGR, CYP11A1, 3ß-HSD1, and NR5A1 in vivo. Taken together, these findings suggest that PFOA inhibits androgen biosynthesis in ILCs by selectively targeting key enzymes in the synthesis pathway.

Removal of a Foley catheter misplaced into the ureter by percutaneous puncture: a rare case report.

BACKGROUND: The incidence of aberrant catheterization into a ureter is extremely low, and there is a 20% chance that the balloon cannot be deflated. Regrettably, the mechanism underlying this complication remains unknown. There has been no reported case of a Foley catheter successfully removed from the ureter via percutaneous puncture. CASE PRESENTATION: A 86-year-old man complained of increasing abdominal pain after an 18F Foley catheter was inserted into his urethra. His attending physician attempted but failed to deflate the balloon. A bedside ultrasound and CT scan revealed that the catheter tip was in the right lower ureter. Several measures, including cutting the catheter and inserting a rigid guidewire, were then attempted but failed to deflate the balloon. Finally, the inflated balloon was punctured with a PTC needle under ultrasound-guidance, and the misplaced Foley catheter was removed. Two days after the pelvic drainage tube was removed, the patient was discharged. CONCLUSION: This is the first reported case of a Foley catheter being removed from the ureter via percutaneous puncture. The mechanism by which the balloon is unable to deflate may be related to the passive twist of the catheter. In such a case, an overall assessment of the patient's condition should be performed, and non-invasive to invasive interventions should be phased in.

Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies.

We performed next generation sequencing on 1696 patients with epilepsy and intellectual disability using a gene panel with 480 epilepsy-related genes including all GABAA receptor subunit genes (GABRs), and we identified six de novo GABR mutations, two novel GABRA5 mutations (c.880G>T, p.V294F and c.1238C>T, p.S413F), two novel GABRA1 mutations (c.778C>T, p.P260S and c.887T>C, p.L296S/c.944G>T, p.W315L) and two known GABRA1 mutations (c.335G>A, p.R112Q and c.343A>G, p.N115D) in six patients with intractable early onset epileptic encephalopathy. The α5(V294F and S413F) and α1(P260S and L296S/W315L) subunit residue substitutions were all in transmembrane domains, while the α1(R112Q and N115R) subunit residue substitutions were in the N-terminal GABA binding domain. Using multidisciplinary approaches, we compared effects of mutant GABAA receptor α5 and α1 subunits on the properties of recombinant α5ß3γ2 and α1ß3γ2 GABAA receptors in both neuronal and non-neuronal cells and characterized their effects on receptor clustering, biogenesis and channel function. GABAA receptors containing mutant α5 and α1 subunits all had reduced cell surface and total cell expression with altered endoplasmic reticulum processing, impaired synaptic clustering, reduced GABAA receptor function and decreased GABA binding potency. Our study identified GABRA5 as a causative gene for early onset epileptic encephalopathy and expands the mutant GABRA1 phenotypic spectrum, supporting growing evidence that defects in GABAergic neurotransmission contribute to early onset epileptic encephalopathy phenotypes.

A Novel Range-Extended Strategy for Fuel Cell/Battery Electric Vehicles.

The range-extended electric vehicle is proposed to improve the range anxiety drivers have of electric vehicles. Conventionally, a gasoline/diesel generator increases the range of an electric vehicle. Due to the zero-CO2 emission stipulations, utilizing fuel cells as generators raises concerns in society. This paper presents a novel charging strategy for fuel cell/battery electric vehicles. In comparison to the conventional switch control, a fuzzy control approach is employed to enhance the battery's state of charge (SOC). This approach improves the quick loss problem of the system's SOC and thus can achieve an extended driving range. Smooth steering experience and range extension are the main indexes for development of fuzzy rules, which are mainly based on the energy management in the urban driving model. Evaluation of the entire control system is performed by simulation, which demonstrates its effectiveness and feasibility.

[Association of mammalian target of rapamycin gene polymorphisms with the risk of pediatric epilepsy].

OBJECTIVE: To study the association between two single nucleotide polymorphisms (SNP), rs2295080 and rs2536, in mammalian target of rapamycin (mTOR) gene and the susceptibility to pediatric epilepsy. METHODS: A case- control study was performed on 480 children with epilepsy (116 cases of refractory epilepsy) and 503 healthy children. SNP rs2295080 and rs2536 in the mTOR gene were detected by polymerase chain reaction restriction and fragment length polymorphisms (PCR-RFLP). Genotype and allele frequencies of SNP rs2295080 and rs2536 were compared between the children with epilepsy and healthy controls. RESULTS: There were no significant differences in the genotype and allele frequencies of SNP rs2295080 between the children with epilepsy and healthy controls. There were no significant differences in the genotype frequencies of SNP rs2536 between the two groups either, but the frequency of G allele of SNP rs2536 was higher in children with epilepsy than that in healthy controls (P=0.042, OR=1.344, 95%CI: 1.010-1.789). CONCLUSIONS: SNP rs2536 of mTOR gene may be associated with the risk of pediatric epilepsy.

Saliva as a sampling source for the detection of leukemic fusion transcripts.

BACKGROUND: Saliva has long been used as a sampling source for clinical diagnosis of oral disease such as oral squamous cell carcinoma, or therapeutic drug monitoring. The aims of this study was to ascertain if saliva RNA could be stored at room temperature and to study if saliva could be a convenient source for fusion transcripts in leukemic patients. METHODS: This is a cross-sectional diagnostic study. We first developed a Saliva RNA tube for stable storage of whole saliva RNA at room temperature. Then we detected the leukemic fusions in the whole saliva from seven leukemic patients and twenty healthy volunteers, and compared with the results obtained from the bone marrow of the patients. RESULTS: Human gene transcripts could be reproducibly detected in the whole saliva for at least four weeks when stored in the developed composition at room temperature. Concordant results of the fusion transcripts were obtained between the saliva and the bone marrow in the seven leukemic patients and no fusions were detected in the healthy controls. CONCLUSIONS: The results support our hypothesis that human whole saliva could be a reliable and convenient sampling source for the detection of leukemic fusions.

Association of HLA-B*1502 and *1511 allele with antiepileptic drug-induced Stevens-Johnson syndrome in central China.

Previous studies have demonstrated a strong association between carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and HLA-B*1502 in Han Chinese. Here, we extended the study of HLA-B*1502 susceptibility to two different antiepileptic drugs, oxcarbazepine (OXC) and phenobarbital (PB). In addition, we genotyped HLA-B*1511 in a case of CBZ-induced SJS with genotype negative for HLA-B*1502. The presence of HLA-B*1502 was determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). Moreover, we genotyped HLA-B*1502 in 17 cases of antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs), in comparison with AEDs-tolerant (n=32) and normal controls (n=38) in the central region of China. The data showed that HLA-B*1502 was positive in 5 of 6 cases of AEDs-induced SJS (4 CBZ, 1 OXC and 1 PB), which was significantly more frequent than AEDs-tolerant (2/32, 18 CBZ, 6 PB and 8 OXC) and normal controls (3/38). Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B*1502 with AEDs-induced SJS was 6.25 (95% CI: 1.06-36.74) and 4.86 (95% CI: 1.01-23.47). The sensitivity and specificity of HLA-B*1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B*1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B*1502 was not found in 11 children with maculopapular exanthema (MPE) (n=9) and hypersensitivity syndrome (HSS) (n=2). However, we also found one case of CBZ-induced SJS who was negative for HLA-B*1502 but carried HLA-B*1511. It was suggested that the association between the CBZ-induced SJS and HLA-B*1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B*1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B*1502.

[Clinical features and MECP2 mutations in children with Rett syndrome].

OBJECTIVE: To study the clinical features and mutations in methyl-CpG-binding protein 2 (MECP2) gene among children with classical Rett syndrome in China. METHODS: PCR and direct sequencing were employed to analyze the three exons of MECP2 gene in 9 children recently diagnosed with Rett syndrome and their parents. RESULTS: Heterozygous mutations were identified in 5 out of 9 patients, with a mutation rate of over 50%; there was one case of insert mutation (c.913insT) and 4 cases of missense mutation (exon 3: c.316C>T (R106W); exon 4: c.502C>T (R168X), c.808C>T (R270X), and c.1126C>T (P376S). A new mutation (c.913insT) was found. No mutations were detected in their parents. Two patients had MECP2 mutations in the transcriptional repression domain (TRD). They had almost lost language functions and were found to have significantly delayed development compared with other patients. CONCLUSIONS: Mutations in MECP2 gene were detected in 5 confirmed cases of Rett syndrome, and most of them were on exon 4. Mutations in the TRD of MECP2 protein may affect the language ability and development in children with Rett syndrome.

Beyond Growth Hormone: Association of Short Stature Types and Growth Hormones With Scoliosis.

STUDY DESIGN: Cross-sectional and retrospective cohort study. OBJECTIVE: We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. SUMMARY OF BACKGROUND DATA: In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. PATIENTS AND METHODS: A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. RESULTS: Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs . 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). CONCLUSIONS: More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. LEVEL OF EVIDENCE: Level III.

Arsenic trioxide inhibits the proliferation of myeloma cell line through notch signaling pathway.

Arsenic Trioxide (ATO) has shown remarkable efficacy for the treatment of multiple myeloma (MM). However, the mechanism by which ATO exerts its inhibitory effect on the proliferation of myeloma cells remains to be clarified. We study the inhibitory effect of ATO at various concentrations on the proliferation of the myeloma cell line RPMI 8226 and discussed the molecular mechanism of ATO on myeloma cell line. Our results proved that ATO had a significant dose-dependent and time-dependent inhibitory effect on the expressions of the Notch receptor (Notch1) and Notch ligand (Jag2). Data from the real-time PCR assay showed that the mRNA expression levels of the Jag2 gene and its downstream gene Hes1 were both significantly down-regulated after the myeloma cells were treated with ATO while the expression of the tumor suppressor gene PTEN was up-regulated. These results elucidated the molecular mechanism underlying the ATO mediated inhibition of myeloma cell proliferation. This is the first report on the anti-myeloma activity in myeloma cells through inhibition of the Notch signaling pathway.

The association between CCL2 polymorphisms and drug-resistant epilepsy in Chinese children.

The treatment of drug-resistant epilepsy remains a major challenge, affecting approximately 30% of epilepsy patients. More recently, immunity and inflammation are considered to be key elements of epilepsy. Targeting brain inflammation may represent a novel therapeutic strategy for epilepsy and refractory epilepsy. In this study, we investigated the association of a tag SNP of the CCL2 gene, rs1024611 (originally designated as -2578G>A or -2518G>A) with drug-resistant epilepsy in Chinese children with epilepsy. We enrolled 484 epilepsy patients, including 98 drug-resistant patients and 386 drug-responsive patients. The rs1024611 was genotyped by PCR-RPLP. The rs1024611 AA genotype was associated with a greater susceptibility to drug-resistant epilepsy (p=0.008; OR=2.51, 95% CI: 1.33-4.72), adjusted for age, sex, and seizure type, and the association remained significant after Bonferroni correction for multiple testing (p<0.05). Our results demonstrate that the CCL2 genetic polymorphism is associated with drug-resistant epilepsy in Chinese paediatric patients.

Persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery: A case report.

BACKGROUND: Empty sella is an anatomical and radiological finding of the herniation of the subarachnoid space into the pituitary fossa leading to a flattened pituitary gland. Patients with empty sella may present with various symptoms, including headache due to intracranial hypertension and endocrine symptoms related to the specific pituitary hormones affected. Here, we report a female patient who developed persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery. CASE SUMMARY: A 47-year-old woman underwent vocal cord polypectomy under general anesthesia with endotracheal intubation. She denied any medical history, and her vital signs were normal before the surgery. Anesthesia and surgery were uneventful. However, she developed dizziness, headache and persistent hypotension in the ward. Thus, intravenous dopamine was started to maintain normal blood pressure, which improved her symptoms. However, she remained dependent on dopamine for over 24 h without any obvious anesthesia- and surgery-related complications. An endocrine etiology was then suspected, and further examination showed a high prolactin level, a low normal adrenocorticotropic hormone level and a low cortisol level. Magnetic resonance imaging of the brain revealed an empty sella. Therefore, she was diagnosed with empty sella syndrome and secondary adrenal insufficiency. Her symptoms disappeared one week later after daily glucocorticoid supplement. CONCLUSION: Endocrine etiologies such as pituitary and adrenal-related dysfunction should be considered in patients showing persistent postoperative hypotension when anesthesia- and surgery-related factors are excluded.

Efficacy and safety of perampanel as early add-on therapy in Chinese patients with focal-onset seizures: a multicenter, open-label, single-arm study.

Background: No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic-clonic seizures (FBTCS) in Chinese patients. Methods: In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded. Results: The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients. Conclusion: Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.Clinical trial registrationwww.chictr.org.cn, Identifier ChiCTR2000039510.

A randomized clinical study of circumcision with a ring device versus conventional circumcision.

PURPOSE: We investigated the safety and efficacy of Shang Ring™ male circumcision and conventional sleeve resection circumcision in a randomized study. MATERIALS AND METHODS: During the same period, 479 cases of Shang Ring circumcision and 354 of sleeve resection circumcision were performed. Complete followup data were evaluated on the 2 groups. Operative time, pain score, blood loss, postoperative complications, wound healing time and treatment costs were compared. RESULTS: There was no statistically significant difference in average age and foreskin status between the 2 groups preoperatively (p >0.05). Compared to the conventional group, there were shorter operative time, less blood loss and a lower intraoperative pain score in the ring group (p <0.05). In addition, ring male circumcision showed a lower complication rate than conventional circumcision (6.89% vs 13.28%, p = 0.002). However, wound healing time in the ring group was longer than in the conventional group (mean ± SD 19.86 ± 5.24 vs 13.42 ± 2.35 days, p <0.001). CONCLUSIONS: Shang Ring male circumcision is a safe, efficient procedure with a relatively low complication rate and high patient satisfaction. It may be worthwhile to popularize this method, especially in countries where the general population has low to limited resources.

[Gene therapy study on bladder cancer with recombinant adenoviral vector carrying LRIG1 gene driven by Survivin promoter].

OBJECTIVE: To investigate the treatment efficiency and mechanism of recombinant adenoviral vector carrying LRIG1 gene driven by Survivin promoter for bladder cancer. METHODS: Human bladder cancer cell line BIU87 and immortalized human bladder epithelial cells SV-HUC-1 were infected with Ad-Surp-LRIG1 and Ad-LRIG, respectively. The selective infection efficiency of Ad-Surp-LRIG1 and Ad-LRIG were evaluated by checking the expression of epidermal growth factor receptor (EGFR). The MTT method was used to test cell growth inhibition ratio of Ad-Surp-LRIG1 and Ad-LRIG. Heterotransplanted models of human bladder cancer cell line BIU87 cells in nude mice were established. The mice were randomly divided into 3 groups during the experiment: Ad-Surp-LRIG1 group received viral supernatant solution of Ad-Surp-LRIG1 by tail vein injection; Ad-LRIG group received viral supernatant solution of Ad-LRIG by tail vein injection; and PBS group received phosphate buffer solution (PBS). The growth of tumors were observed and the growth curve was mapped. The expression of LRIG1 and EGFR were examined by reverse transcription PCR (RT-PCR). RESULTS: When Multiplicity of infection was 25, the transfection efficiency of Ad-Surp-LRIG1 was 74.56% in BIU87 cells and 0 in SV-HUC-1 cells (χ² = 58.640, P = 0.000), while the transfection efficiency of Ad-LRIG was 68.27% in BIU87 cells and 72.52% in SV-HUC-1 cells (χ² = 0.075, P = 0.784). The transfection efficiency difference of Ad-Surp-LRIG1 and Ad-LRIG in BIU87 cells was not statistically significant (χ² = 0.016, P = 0.898). Compared with PBS, Ad-Surp-LRIG1 and Ad-LRIG1 could inhibit BIU87 cell growth, the difference was significant in 4 days after transfection (F = 15.960, P = 0.000). There was not significant difference in cell growth rate of Ad-Surp-LRIG1 group and Ad-LRIG1 group. The tumor growth rate in Ad-Surp-LRIG1 group was slower than that in the other 2 groups. The tumor quality in Ad-Surp-LRIG1 was lighter than that in the other two groups, the differences were statistically significant (F = 97.860, P = 0.000), the quality difference in Ad-LRIG1 group and PBS group was not statistically significant difference (t = 1.73, P = 0.06). Compared with Ad-LRIG1 group and PBS group, the mRNA expression of LRIG1 was obviously up-regulated and that of EGFR was down-regulated in Ad-Surp-LRIG1 group (P < 0.01). CONCLUSIONS: The recombinant adenoviral vector of Ad-Surp-LRIG1 could selectively transfected BIU87 cells, which could inhibit significantly the growth of bladder cancer in vivo and in vitro, the mechanism may be partly LRIG1 can downgrade the expression of EGFR.

Computed Tomography Angiography and Three-Dimensional Reconstruction of Renal Arteries in Diagnosing the Bleedings After Mini-Percutaneous Nephrolithotomy: A Single-center Experience of 7 Years.

OBJECTIVE: This study aimed to investigate the role of computed tomography angiography (CTA) and three-dimensional (3D) reconstruction of renal arteries in the evaluation of bleeding after mini- percutaneous nephrolithotomy (PCNL). METHODS: Thirty-one consecutive patients with continuous renal hemorrhage after mini-PCNL were enrolled from January 2015 to January 2022. Demographic and clinical data were retrospectively recorded and analyzed. All patients had received CTA evaluation and subsequently digital subtraction angiography (DSA) embolization to manage renal bleeding. CTA and 3D reconstruction of renal arteries were performed using the 320 multi-detector computed tomography technique and the images were evaluated by experienced radiologists. DSA embolization were performed by an interventional radiologist with more than 10 years of experiences. RESULTS: CTA and 3D construction of renal arteries showed 28 cases of vascular lesions (28/31, 90.3%), including 15 cases of pseudoaneurysm (15/28, 53.6%), 9 cases of arteriovenous fistula (9/28, 32.1%), and 4 cases of suspicious bleeding spot (4/28, 14.3%). While DSA revealed 31 cases of vascular lesions (100%), including 15 cases of pseudoaneurysm (15/31, 48.4%), 10 cases of arteriovenous fistula (10/31, 32.3%), 6 cases of bleeding spot and (6/31, 19.4%). The serum creatinine level was elevated slightly before mini-PCNL and after DSA embolization (73.1±18.1 vs 92.1±33.6, P <.01). 15 patients (15/31, 48.4%) required blood transfusion, with mean blood transfusion volume of 700 ml ±660 ml (range, 400 ml-1800 ml). The bleeding was controlled without any further severe complications. CONCLUSION: CTA and 3D reconstruction of renal arteries were safe and effective in diagnosing renal arterial bleedings after mini-PCNL, with a sensitivity of 90.3% and a specificity of 100%.

[Effects of TNF-α on ICAM-1 and LFA-1 expression in peripheral blood mononuclear cells of children with febrile seizures].

OBJECTIVE: To study the effects of TNF-α on ICAM-1 and LFA-1 expression in peripheral blood mononuclear cells (PBMC) of children with febrile seizures (FS). METHODS: Sixteen children with FS and 16 age- and gender-matched healthy children were enrolled. The samples of PBMC from FS children were randomized into two groups with or without TNF-α treatment (TNF-α concentration 1.0 ng/mL). PBMC were purified and cultured with a conventional method in vitro. The expression of ICAM-1 and LFA-1 in PBMC was determined by flow cytometry (FCM). RESULTS: ICAM-1ï¼»(20±9)% vs (14±7)%)ï¼½and LFA-1ï¼»(43±16)% vs (30±16)%ï¼½expression in PBMC in the untreated FS group was significantly higher than that in the normal control group (P<0.05). Compared with the untreated FS group, the treatment with TNF-α remarkably increased the ICAM-1 expressionï¼»(27±11)%ï¼½(P<0.05). PBMC LFA-1 expressionï¼»(52±21)%ï¼½in the TNF-α-treated group was higher than that in the untreated FS group, although there were no statistical differences between the two groups. CONCLUSIONS: TNF-α treatment may increase LFA-1 and ICAM-1 expression in PBMC of children with FS.

Treatment with melatonin ameliorates febrile convulsion via modulating the MEG3/miR­223/PTEN/AKT signaling pathway.

The PTEN/AKT signaling pathway is involved in the pathogenesis of febrile convulsion (FC), a convulsion caused by abnormal electrical activity in the brain. The objective of the present study was to evaluate the therapeutic effect of melatonin (MT) on FC and the according underlying molecular mechanisms. Reverse transcription­quantitative PCR and western blot analysis were used to explore the effects of MT on the expression levels of MEG3, microRNA (miRNA/miR)­223, phosphatase and tensin homolog (PTEN) and protein kinase B (AKT). Luciferase assay was performed to verify the downstream targets of MEG3 and miR­223. An animal model was established to evaluate the effects of MT on the MEG3/miR­223/PTEN/AKT pathway. TUNEL staining was carried out to assess the effect of MT on neuronal apoptosis. Finally, the duration of seizure/convulsion was recorded to determine the effect of MT on FC. In both cell and animal models, mRNA levels of MEG3 and PTEN increased in the apoptosis group, while treatment with MT decreased the expression levels of MEG3 and PTEN. miR­223 expression was decreased in the apoptosis group, whereas treatment with MT increased the expression level of miR­223. Protein levels of PTEN and cleaved caspase­3 increased in the apoptosis group, whereas treatment with MT decreased the protein level of PTEN. Phosphorylated (p)­AKT expression was decreased in the apoptosis group and treatment with MT reversed this effect. miR­223 could directly bind to MEG3, and PTEN was a direct target of miR­223. MT could decrease the duration of seizure/convulsion. In all experimental groups, treatment with MT could decrease the ratio of ß waves, while increasing the ratios of α, θ and δ waves. Therefore, the results from the present study collectively suggested that treatment with MT alleviated FC via the MEG3/miR­223/PTEN/AKT pathway, which also indicated that MT could be considered as a novel strategy for the treatment of FC disease.

The Clinical and Imaging Characteristics Associated With Neurological Sequelae of Pediatric Patients With Acute Necrotizing Encephalopathy.

Background: Acute necrotizing encephalopathy of childhood (ANE) is a rare but rapidly progressing encephalopathy. Importantly, the exact pathogenesis and evidence-based treatment is scarce. Thus, we aimed to identify the clinical, imaging, and therapeutic characteristics that associated with prognosis of pediatric ANE patients. Methods: A retrospective study was conducted on pediatric patients with ANE who were admitted to Wuhan Children's Hospital between January 2014 and September 2019. All cases met the diagnostic criteria for ANE proposed by Mizuguchi in 1997. The clinical information and follow-up data were collected. The prognostic factors were analyzed by trend chi-square test and Goodman-Kruskal gamma test. Results: A total of 41 ANE patients ranging in age from 8.9 to 142 months were included in this study. Seven cases (17%) died, and the other 34 survivors had different degrees of neurological sequelae. Factors tested to be significantly correlated with the severity of neurological sequelae were the intervals from prodromal infection to acute encephalopathy (G = -0.553), conscious disturbance (r = 0.58), endotracheal intubation (r = 0.423), elevation of alanine aminotransferase (r = 0.345), aspartate aminotransferase (r = 0.393), and cerebrospinal fluid protein (r = 0.490). In addition, dynamic magnetic resonance imaging (MRI) evaluation on follow-up revealed that the total numbers of brain lesion location (χ2 = 6.29, P < 0.05), hemorrhage (r = 0.580), cavitation (r = 0.410), and atrophy (r = 0.602) status were significantly correlated with the severity of neurological sequelae, while early steroid therapy (r = -0.127 and 0.212, respectively) and intravenous immunoglobulin (IVIG) (r = 0.111 and -0.023, respectively) within 24 h or within 72 h after onset showed no association. Conclusions: Intervals from prodromal infection to acute encephalopathy (≤1 day), total numbers of brain lesion location (≥3), the recovery duration of hemorrhage and atrophy (>3 months), and the presence of cavitation predict severe neurological sequelae in pediatric patients with ANE. Early treatments, including steroid therapy and IVIG, had no correlation with better outcomes. Further studies are needed to establish a consensus guideline for the management of ANE.