Comprehensive Proteomics Analysis Identifies CD38-Mediated NAD+ Decline Orchestrating Renal Fibrosis in Pediatric Patients With Obstructive Nephropathy.

Obstructive nephropathy is one of the leading causes of kidney injury and renal fibrosis in pediatric patients. Although considerable advances have been made in understanding the pathophysiology of obstructive nephropathy, most of them were based on animal experiments and a comprehensive understanding of obstructive nephropathy in pediatric patients at the molecular level remains limited. Here, we performed a comparative proteomics analysis of obstructed kidneys from pediatric patients with ureteropelvic junction obstruction and healthy kidney tissues. Intriguingly, the proteomics revealed extensive metabolic reprogramming in kidneys from individuals with ureteropelvic junction obstruction. Moreover, we uncovered the dysregulation of NAD+ metabolism and NAD+-related metabolic pathways, including mitochondrial dysfunction, the Krebs cycle, and tryptophan metabolism, which led to decreased NAD+ levels in obstructed kidneys. Importantly, the major NADase CD38 was strongly induced in human and experimental obstructive nephropathy. Genetic deletion or pharmacological inhibition of CD38 as well as NAD+ supplementation significantly recovered NAD+ levels in obstructed kidneys and reduced obstruction-induced renal fibrosis, partially through the mechanisms of blunting the recruitment of immune cells and NF-κB signaling. Thus, our work not only provides an enriched resource for future investigations of obstructive nephropathy but also establishes CD38-mediated NAD+ decline as a potential therapeutic target for obstruction-induced renal fibrosis.

Design and demonstration of high-power density infrared nonlinear filtering window with EM shielding.

Directional energy weapons such as high-power microwaves and high-energy lasers pose a huge threat to optoelectronic detection systems. With that in mind, we designed an infrared optical window that has a nonlinear optical response to high-energy lasers and electromagnetic shielding to microwaves. By constructing a periodic metal circular hole array structure at the subwavelength scale, surface plasmons resonance is excited and its local field enhanced characteristics are utilized to form information transmission compatibility in the infrared band. At the same time, after laser etching off the subwavelength structure, the remaining metal forms a continuous conductive structure, forming an ultra-wideband shielding layer to achieve ultra-high and wide protection in the microwave band. Moreover, a layer of Ge2Sb2Te5 thin film was deposited between the transparent substrate and the metal film. Utilizing its nonlinear optical properties of high-temperature phase transition to reduce damage of directed energy weapons to the photoelectric detection system and equipment. Thus, when the photoelectric detection system or device is damaged or interfered by signals of different frequency bands or energies, the filtering window can achieve multi-mode shielding function.

Hsa-miR-3178/RhoB/PI3K/Akt, a novel signaling pathway regulates ABC transporters to reverse gemcitabine resistance in pancreatic cancer.

BACKGROUND: Although gemcitabine has been considered as the first-line drug for advanced pancreatic cancer (PC), development of resistance to gemcitabine severely limits the effectiveness of this chemotherapy, and the underlying mechanism of gemcitabine resistance remains unclear. Various factors, such as ATP binding cassette (ABC) transporters, microRNAs and their downstream signaling pathways are included in chemoresistance to gemcitabine. This study investigated the potential mechanisms of microRNAs and ABC transporters related signaling pathways for PC resistance to gemcitabine both in vivo and in vitro. METHODS: Immunohistochemistry and Western blotting were applied to detect the expression of ABC transporters. Molecular docking analysis was performed to explore whether gemcitabine interacted with ABC transporters. Gain-of-function and loss-of-function analyses were performed to investigate the functions of hsa-miR-3178 in vitro and in vivo. Bioinformatics analysis, Western blotting and dual-luciferase reporter assay were used to confirm the downstream regulatory mechanisms of hsa-miR-3178. RESULTS: We found that P-gp, BCRP and MRP1 were highly expressed in gemcitabine-resistant PC tissues and cells. Molecular docking analysis revealed that gemcitabine can bind to the ABC transporters. Hsa-miR-3178 was upregulated in gemcitabine resistance PANC-1 cells as compared to its parental PANC-1 cells. Moreover, we found that hsa-miR-3178 promoted gemcitabine resistance in PC cells. These results were also verified by animal experiments. RhoB was down-regulated in gemcitabine-resistant PC cells and it was a downstream target of hsa-miR-3178. Kaplan-Meier survival curve showed that lower RhoB expression was significantly associated with poor overall survival in PC patients. Rescue assays demonstrated that RhoB could reverse hsa-miR-3178-mediated gemcitabine resistance. Interestingly, hsa-miR-3178 promoted gemcitabine resistance in PC by activating the PI3K/Akt pathway-mediated upregulation of ABC transporters. CONCLUSIONS: Our results indicate that hsa-miR-3178 promotes gemcitabine resistance via RhoB/PI3K/Akt signaling pathway-mediated upregulation of ABC transporters. These findings suggest that hsa-miR-3178 could be a novel therapeutic target for overcoming gemcitabine resistance in PC.

[Clinical evaluation of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children].

OBJECTIVE: To evaluate the clinical efficacy of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children. METHODS: From January to December 2020, we treated 116 children with distal hypospadias in the Department of Urology, Department of Pediatrics and the Seventh Medical Center of the PLA General Hospital, 58 by primary Snodgrass urethroplasty only (the control group) and the other 58 with Compound Chamomile and Lidocaine Hydrochloride Gel smeared on the penis postoperatively in addition (the trial group). We compared the operation time and postoperative pain score, edema regression and incidence of infection between the two groups, followed by statistical analysis using T test and Chi-square test. RESULTS: All the operations were successfully completed by the same surgeon under general anesthesia. There were no statistically significant differences between the trial and control groups in age (ï¼»2.5 ± 0.8ï¼½ vs ï¼»2.4 ± 0.6ï¼½ yr, P > 0.05) or operation time (ï¼»95.6 ± 14.5ï¼½ vs ï¼»97.1 ± 15.2ï¼½ min, P > 0.05). No incision infection occurred in any of the cases. The pain scores at dressing removal were remarkably lower in the trial than in the control group at 2 hours (1.4 ± 1.0 vs 2.6 ± 1.3, P < 0.05), 24 hours (2.2 ± 1.3 vs 3.9 ± 1.6, P < 0.05), 48 hours (1.2 ± 0.7 vs 1.6 ± 0.9, P < 0.05) and 72 hours after surgery (2.5 ± 0.8 vs 3.7 ± 1.8, P < 0.05). Significantly more cases of edema regression were achieved in the trial than in the control group at 2 weeks postoperatively (35 vs 19, P < 0.05). CONCLUSIONS: Compound Chamomile and Lidocaine Hydrochloride Gel can effectively relieve pain, reduce edema and accelerate edema regression after surgery in children with hypospadias, and therefore deserves wide clinical application.、.

Non-invasive detection of glucose via a solution-gated graphene transistor.

Owing to its high sensitivity, a solution-gated graphene transistor has rapidly emerged as a cutting edge technology in electrochemical sensing. In this work, composites of gold nanoparticles and reduced graphene oxide were synthesized on a glassy carbon electrode by using the electrodeposition method. A modified glassy carbon electrode was used as the gate electrode and assembled into the solution-gated graphene transistor device along with the graphene channel for a non-invasive glucose detection. The sensing mechanism was based on the change in current in the channel of the device caused by the addition of glucose, of which electro-oxidation on the surface of the gold nanoparticles and reduced graphene oxide led to a change in equivalent gate voltage, and consequently, affected the channel carrier concentration. The self-amplification effect of transistors was utilized in our sensors, which resulted in a detection limit that was 10 times lower than those of conventional electrochemical sensors. Compared to traditional enzymatic transistor sensors, the novel solution-gated graphene transistor nonenzymatic sensors based on gold nanoparticles and reduced graphene oxide demonstrated significant sensing advantages, such as a simple structure, wide linear range from 10 µM to 400 µM and 400 µM to 31 mM, and low detection limit down to 4 µM. The chemicals coexisting in human sweat e.g. sodium chloride, urea, and lactic acid imposed no distinct interference for the glucose detection. Therefore, we achieved a non-invasive detection of glucose in the artificial sweat samples with satisfactory sensing results. This work demonstrates an effective route for non-invasive glucose testing in practical clinical diagnosis by using nonenzymatic, solution-gated graphene transistor devices.

A Randomized Controlled Trial of Comparing Ultrasound-Guided Transversus Abdominis Plane Block with Local Anesthetic Infiltration in Peritoneal Dialysis Catheter Implantation.

BACKGROUND: The ultrasound-guided transversus abdominis plane (TAP) block has been demonstrated as a useful analgesia technique in lower-abdomen surgeries. We hypothesized that it could be the principal anesthesia technique for end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD) catheter (PDC) implantation using the open dissection method. METHODS: This was a single-center, prospective, randomized, and double-blinded study. All eligible patients were randomized into 2 groups: the TAP block group (n = 20) and the local anesthetic infiltration (LAI) group (n = 20). RESULTS: Compared with the LAI group, the TAP block group revealed a remarkably lower visual analogue score, lower switching rate into general anesthesia, higher satisfaction rate, and less rescuing analgesic consumption during operation (p < 0.05). Both PD- and anesthesia-related complications were rare in the 4-week follow-up. CONCLUSIONS: The ultrasound-guided TAP block had better analgesic effect than LAI and can be used as a principal anesthesia technique for PDC implantation in ESRD patients without previous abdominal surgery.

Marinibaculum pumilum gen. nov., sp. nov., isolated from seawater.

A Gram-stain-negative, facultatively anaerobic, motile and rod-shaped strain, designed H2T, was isolated from the Western Pacific Ocean, and subjected to a taxonomic investigation using a polyphasic approach. Strain H2T grew at 15-40 °C and pH 6.0-9.0 (optimum 37 °C and pH 6.5), and with 1-10 % (w/v) NaCl (optimum 2 %). The predominant respiratory quinone was ubiquinone-10 (Q-10) and the major fatty acids identified were C19 : 0 cyclo ω8c, C18 : 1ω7c, C18 : 0 and 11-methyl-C18 : 1ω7c. The polar lipids of strain H2T consisted of phosphatidylglycerol, one unknown phospholipid, one unknown glycolipid and three unidentified aminolipids. The DNA G+C content was 75.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain H2T formed a distinct clade belong to the family Rhodospirillaceae within the Alphaproteobacteria. On the basis of morphological, physiological and chemotaxonomic characteristics, together with the results of phylogenetic analysis, strain H2T represents a novel species in a new genus in the family Rhodospirillaceae, for which the name Marinibaculumpumilum gen. nov., sp. nov. is proposed. The type strain of the type species is H2T(=MCCC 1K02279T=KCTC 42964T).

Role of Halloween genes in ecdysteroids biosynthesis of the swimming crab (Portunus trituberculatus): Implications from RNA interference and eyestalk ablation.

Molting, including metamorphosis molting in arthropods are controlled by the ecdysteroids that are synthesized and secreted by the crustacean Y-organ (YO) or the insect prothoracic gland (PG). The Halloween genes encoding the enzymes mainly involved in the biosynthesis of ecdysteroids are well studied in insects but not in crustaceans. Given the importance of Halloween genes in ecdysteroids biosynthesis, we have previously reported the cDNA cloning of disembodied (Dib) in P. trituberculatus. Here, cDNA sequences of another two Halloween genes, Spook (Spo) and Shadow (Sad), were further identified and characterized. The predicted amino acid sequences for these two Halloween genes of Portunus trituberculatus were compared to those of several other arthropods, and several typical domains of the cytochrome P450 mono-oxygenase (CYP) were identified. Similar to the tissue distribution of Dib, the Spo and Sad also showed high specificity to the YO. RNA interference (RNAi) of these 3 genes indicated they all play essential role in ecdysteroids biosynthesis. To investigate the relationships of the Halloween genes to the eyestalk neuropeptides such as molt-inhibiting hormone (MIH), effects of eyestalk ablation (ESA) on the expression of Dib, Spo and Sad were detected. Expression of Dib and Sad, but not Spo, was significantly induced by ESA. The result indicated that the inhibition of MIH in ecdysteroids biosynthesis may be partly through the transcriptional regulation of certain Halloween genes, such as Dib and Sad, while the Spo might not be the target for MIH signal.

A modified technique of paraumbilical three-port laparoscopic dismembered pyeloplasty for infants and children.

BACKGROUND: Common causes of complications of laparoscopic pyeloplasty in children include anastomotic stricture, poor drainage due to high ureteropelvic anastomosis, and torsion of ureter. Herewith, we described our modified technique of paraumbilical three-port laparoscopic dismembered pyeloplasty (PTLDP) to minimize these complications. PATIENTS AND METHODS: Data from 62 patients (age: 1-180 months, median: 12 months) with ureteropelvic junction obstruction (UPJO) who underwent pyeloplasty using our modified technique of PTLDP between February 2014 and September 2014 at our institution were reviewed. The key steps of our modified method involve identifying the lowest point of the renal pelvis and the lateral aspect of the ureter to guarantee a low pelviureteric and correct orientation anastomosis, and using a 4-0 silk for assistant suturing to avoid crushing of the anastomotic tissue. RESULTS: All surgeries were successfully completed without conversion. Three patients required an accessory port for the anastomosis. All the patients achieved complete clinical or radiologic resolution after the operation. The mean operative time was 103.4 min, and mean estimated blood loss was 14.4 mL. Mean postoperative differential function of affected kidney was 43.0 ± 16.3 % (range 24-100 %), increased from 39.7 ± 18.0 % (range 18-100 %), preoperatively (p < 0.001). The success rate was 100 % at a mean follow-up of 18.3 ± 2.9 (range 13-25) months. CONCLUSIONS: Our modified technique of PTLDP is safe and feasible and to allow high success rate for the treatment of pelviureteric junction obstruction in children.

Myofibrillogenesis regulator-1 attenuated hypoxia/reoxygenation-induced apoptosis by inhibiting the PERK/Nrf2 pathway in neonatal rat cardiomyocytes.

The purpose of this study was to investigate the role of myofibrillogenesis regulator-1 (MR-1) in cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R), through protein kinase R-like ER kinase (PERK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. To address this aim, an H/R model of neonatal rat cardiomyocytes was used. MR-1 was overexpressed using an adenoviral vector system and knocked down using MR-1 specific siRNA. Apoptosis was assessed by using Annexin V/PI double staining, terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling assay, and the Bcl-2/Bax ratio. Western blotting was used to detect the protein levels of MR-1, glucose-regulated protein 78 (GRP78), total and phosphorylated PERK, Nrf2, activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), Bcl-2 and Bax. Immunofluorescence staining was used to assess the subcellular location of Nrf2. We found that H/R induced significant apoptosis in neonatal rat cardiomyocytes. MR-1 overexpression attenuated H/R-induced apoptosis, decreased GRP78 (P < 0.01) and CHOP expression (P < 0.05), and increased the Bcl-2/Bax ratio (P < 0.01). MR-1 overexpression suppressed H/R-induced PERK phosphorylation, Nrf2 nuclear translocation, and ATF4 expression (P < 0.01). While MR-1 knockdown aggravated H/R-induced apoptosis, increased expression of GRP78 and CHOP (P < 0.05), and decreased the Bcl-2/Bax ratio (P < 0.01). MR-1 knockdown significantly increased H/R-induced PERK phosphorylation (P < 0.05), Nrf2 nuclear translocation, and ATF4 expression (P < 0.01). These findings suggest that MR-1 alleviates H/R-induced cardiomyocyte apoptosis through inhibition of the PERK/Nrf2 pathway.

Panax quinquefolium saponin attenuates cardiomyocyte apoptosis and opening of the mitochondrial permeability transition pore in a rat model of ischemia/reperfusion.

AIMS: Opening of the mitochondrial permeability transition pore (mPTP) is a critical event during ischemia/reperfusion (I/R) injury. Recently, we showed that Panax quinquefolium saponin (PQS) alleviates apoptosis of cardiomyocytes by suppressing excessive endoplasmic reticulum stress (ERS) during I/R injury. Here, we hypothesized that this anti-apoptotic effect might be mediated through inhibition of mPTP and the mitochondrial apoptotic pathway. METHODS: Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham, I/R, I/R+PQS (200 mg/kg/d), Cyclosporine A (CsA, 10 mg/kg), I/R+CsA (10 mg/kg), and I/R+PQS+CsA. I/R was modeled in rats by ligating the left anterior descending artery (LAD) for 30 min followed by 120 min of reperfusion. To evaluate the cardioprotective function of PQS, we measured hemodynamics, serum content of creatine kinase-MB (CK-MB), myocardial infarct size, and myocardial apoptotic index (AI). We investigated the underlying mechanism by examining changes in the mitochondrial ultrastructure and membrane potential (ΔΨm), dynamics of mPTP opening, expression of cleaved caspase-3, cleaved caspase-9 in the myocardium, Bcl-2 and Bax in the mitochondria versus cytosol, and translocation of cytochrome c. RESULTS: Administration of PQS to I/R rats significantly reduced serum CK-MB level, infarct size and AI. In addition, PQS protected the mitochondrial structure, markedly inhibited mPTP opening and ΔΨm depolarization, led to upregulation of Bcl-2 and downregulation of Bax in the mitochondria compared to the cytosol, and suppressed the expression of cleaved caspase-9 and cleaved caspase-3, as well as I/R induced translocation of cytochrome c to the cytoplasm. CONCLUSION: Our results show that PQS can alleviate apoptosis of cardiomyocytes during I/R injury, possibly due to repressed mitochondrial apoptotic pathway associated with the opening of mPTP induced by myocardial I/R injury.

Cytosolic calreticulin inhibits microwave radiation-induced microvascular endothelial cell injury through the integrin-focal adhesion kinase pathway.

OBJECTIVE: To determine the effects of cytosolic CRT on MR-induced MMEC injury, and the underlying mechanism. METHODS: MMECs were randomized into eight groups: control, AdCRT (infected with pAdCMV/V5-DEST-CRT adenovirus), stCRT (transfected with rCRT-siRNAs), Mock (transfected with scrambled siRNAs), MR (exposed to MR for six minutes), AdCRT + MR, stCRT + MR, and Mock + MR. The magnitude of cell injury were assessed by Annexin V-PI staining, LDH activity in culture medium, MMEC migration ability, ultrastructure and cytoskeletal stability. Subcellular colocalization of CRT and ConA or integrin were evaluated by immunocytochemistry. The mRNA and protein expression levels of target genes were examined by qRT-PCR and western blotting, respectively. RESULTS: MR-induced cytotoxicity was dose-dependent. Overexpression of cytosolic CRT suppressed MR injury, shown as decreased cell apoptosis, reduced LDH activity, enhanced cell migration capability, and maintenance of ultrastructure and cytoskeleton integrity. Conversely, CRT deficiency aggravated MR-induced injury. Exposure of AdCRT MMECs to MR promoted membrane translocation of CRT and the interaction of CRT-integrin-α. Correlation analysis revealed that integrin-α expression or FAK phosphorylation was positively associated with cytosolic CRT expression. CONCLUSIONS: Cytosolic CRT inhibits MR-induced MMEC injury through activation of the integrin-FAK pathway.

Blockade of ICAM-1 improves the outcome of polymicrobial sepsis via modulating neutrophil migration and reversing immunosuppression.

Intercellular adhesion molecule-1 (ICAM-1) is a key adhesion molecule mediating neutrophil migration and infiltration during sepsis. But its role in the outcome of sepsis remains contradictory. The current study was performed to investigate the role of anti-ICAM-1 antibody in the outcome of polymicrobial sepsis and sepsis-induced immune disturbance. Effect of anti-ICAM-1 antibody on outcome of sepsis induced by cecal ligation and puncture (CLP) was evaluated by the survival analysis, bacterial clearance, and lung injury. Its influence on neutrophil migration and infiltration, as well as lymphocyte status, in thymus and spleen was also investigated. The results demonstrated that ICAM-1 mRNA was upregulated in lung, thymus, and spleen of CLP mice. Anti-ICAM-1 antibody improved survival and bacterial clearance in CLP mice and attenuated lung injury. Migration of neutrophils to peritoneal cavity was enhanced while their infiltration into lung, thymus, and spleen was hampered by ICAM-1 blockade. Anti-ICAM-1 antibody also prevented sepsis-induced apoptosis in thymus and spleen. Positive costimulatory molecules including CD28, CD80, and CD86 were upregulated, while negative costimulatory molecules including PD-1 and PD-L1 were downregulated following anti-ICAM-1 antibody administration. In conclusion, ICAM-1 blockade may improve outcome of sepsis. The rationale may include the modulated neutrophil migration and the reversed immunosuppression.

High-Performance Ni3(HHTP)2 Film-Based Flexible Field-Effect Transistor Gas Sensors.

Conductive metal-organic frameworks (MOFs) have received increasing attention in recent years and present high application potential as sensing elements in electronic sensors. In this study, flexible field-effect transistor (FET) sensors based on conductive MOF, i.e., Ni3(HHTP)2, have been constructed. This Ni3(HHTP)2 sensor has high sensitivity (detection limit of 56 ppb) as well as superior selectivity for NO2 detection at room temperature, which is demonstrated by accurate gas detection in a mixed gas atmosphere. Moreover, by employing six flexible substrates, i.e., polyimide (PI), tape (PET), facemask, paper cup, tablecloth, and take-out bag (textile), we successfully demonstrate the universality of the flexible sensor construction with conductive MOF as sensing film on various substrates. This study of conductive MOF-based flexible electronic sensors offers a new opportunity for a wide range of sensing applications with wearable and portable electronic devices.

Investigating the causal relationship and potential shared diagnostic genes between primary biliary cholangitis and systemic lupus erythematosus using bidirectional Mendelian randomization and transcriptomic analyses.

Background: The co-occurrence of primary biliary cholangitis (PBC) and systemic lupus erythematosus (SLE) has been consistently reported in observational studies. Nevertheless, the underlying causal correlation between these two conditions still needs to be established. Methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to assess their causal association. Five MR analysis methods were utilized for causal inference, with inverse-variance weighted (IVW) selected as the primary method. The Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and the IVW Radial method were applied to exclude outlying SNPs. To assess the robustness of the MR results, five sensitivity analyses were carried out. Multivariable MR (MVMR) analysis was also employed to evaluate the effect of possible confounders. In addition, we integrated transcriptomic data from PBC and SLE, employing Weighted Gene Co-expression Network Analysis (WGCNA) to explore shared genes between the two diseases. Then, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment methods to perform on the shared genes. The Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was utilized to identify potential shared diagnostic genes. Finally, we verified the potential shared diagnostic genes in peripheral blood mononuclear cells (PBMCs)-specific cell populations of SLE patients by single-cell analysis. Results: Our MR study provided evidence that PBC had a causal relationship with SLE (IVW, OR: 1.347, 95% CI: 1.276 - 1.422, P < 0.001) after removing outliers (MR-PRESSO, rs35464393, rs3771317; IVW Radial, rs11065987, rs12924729, rs3745516). Conversely, SLE also had a causal association with PBC (IVW, OR: 1.225, 95% CI: 1.141 - 1.315, P < 0.001) after outlier correction (MR-PRESSO, rs11065987, rs3763295, rs7774434; IVW Radial, rs2297067). Sensitivity analyses confirmed the robustness of the MR findings. MVMR analysis indicated that body mass index (BMI), smoking and drinking were not confounding factors. Moreover, bioinformatic analysis identified PARP9, ABCA1, CEACAM1, and DDX60L as promising diagnostic biomarkers for PBC and SLE. These four genes are highly expressed in CD14+ monocytes in PBMCs of SLE patients and potentially associated with innate immune responses and immune activation. Conclusion: Our study confirmed the bidirectional causal relationship between PBC and SLE and identified PARP9, ABCA1, CEACAM1, and DDX60L genes as the most potentially shared diagnostic genes between the two diseases, providing insights for the exploration of the underlying mechanisms of these disorders.

Robot-Assisted Ureteroplasty with Labial Mucosal Onlay Grafting for Long Left-Sided Proximal Ureteral Stenosis in Children and Adolescents: Technical Tips and Functional Outcomes.

Purpose: To evaluate functional outcomes of robot-assisted ureteroplasty with labial mucosa grafting for long proximal ureteral stenosis (LPUS) in children and adolescents. Methods: Included in this study were 15 patients who underwent robot-assisted ureteroplasty with labial mucosal grafting in our center between July 2017 and September 2021. The left affected stenotic ureter was repaired using labial mucosal grafting. If the ureter was simply strictured but not obliterated, the ureter was spatulated longitudinally along the ventral side and the labial mucosa graft was interposed and anastomosed in a continuous manner. Faced with the obliterated segment, it was excised and the spatulated portion re-anastomosed with a pelvic flap as the dorsal wall. The labial mucosa graft was placed as the ventral wall. The preoperative clinical data and follow-up outcomes were collected and evaluated. Results: Labial mucosa graft onlay ureteroplasty was well performed in all the 15 patients with no occurrence of intraoperative complications or surgical conversion. Five patients underwent an onlay ureteroplasty, and 10 patients underwent a dorsally augmented pelvic flap anastomotic ureteroplasty. The mean (range) stricture length was 7.1 (3-10) cm. The mean operative time was 371.2 (216-480) minutes, and the median blood loss was 40 mL. At the median follow-up of 35 months (range 12-58 months), the overall success rate was 93.3%. Conclusions: Labial mucosa grafting appears to be safe and feasible for repairing long ureteral strictures in pediatric and adolescent patients. Our experience may provide beneficial references and conveniences to solve complex problems in LPUS. This study was approved by the institutional review board, and written informed consent was obtained from each participant (ethics number: 2017-30).

Robotic-assisted laparoscopic surgery for the treatment of Wilms' tumor in children: single-center experience and medium-term outcomes.

To report our institutional experience and the medium-term outcomes of utilizing robotic-assisted laparoscopic surgery (RALS) in patients with Wilms' tumor (WT). The robotic surgical interventions include nephron-sparing surgery (RAL-NSS), radical nephrectomy (RAL-RN), and nephrectomy with inferior vena cava thrombectomy (RAL-N-IVCT). We retrospectively collected medical records of WT patients who underwent RALS in our center between August 2019 and February 2022. Patients' baseline demographics, preoperative parameters, and perioperative/postoperative data were recorded and analyzed. Follow-up results were collected to evaluate the oncological outcomes. A total of 12 patients (13 sides) with a median age of 30 (IQR: 19.5-45.5) months were included. All operations were successfully completed without conversion. Seven patients received preoperative chemotherapy. Distribution of surgical interventions was as follows: five patients underwent RAL-RN, five received RAL-NSS, one with bilateral WT underwent concurrent RAL-RN and RAL-NSS, and one received RAL-RN-IVCT post preoperative chemotherapy. Postoperative chemotherapy was conducted in ten patients. The estimated intraoperative blood loss was 27 ± 4.0 ml for the RAL-NSS group, 41.67 ± 12.13 ml for the RAL-RN group, and 350 ml for the RAL-RN-IVCT groups, respectively. The median perioperative serum creatinine levels were 32.5 (IQR: 30.75-39.5) µmol/l preoperatively and 35 (IQR: 31.75-38.5) µmol/l postoperatively, which showed no significant difference. No positive lymph nodes were detected. Postoperative chemotherapy was performed according to the tumor volume and pathological findings. The median follow-up time was 17.5 (15.8-22.3) months. During this interval, neither distant metastasis nor recurrence was identified. Based on our medium-term follow-up observations, RAL-NSS, RAL-RN, and RAL-RN-IVCT exhibit promising feasibility and safety profiles in the therapeutic landscape of WT.

Gastric mechanosensitive channel Piezo1 regulates ghrelin production and food intake.

Ghrelin, produced mainly by gastric X/A-like cells, triggers a hunger signal to the central nervous system to stimulate appetite. It remains unclear whether X/A-like cells sense gastric distention and thus regulate ghrelin production. Here we show that PIEZO1 expression in X/A-like cells decreases in patients with obesity when compared to controls, whereas it increases after sleeve gastrectomy. Male and female mice with specific loss of Piezo1 in X/A-like cells exhibit hyperghrelinaemia and hyperphagia and are more susceptible to overweight. These phenotypes are associated with impairment of the gastric CaMKKII/CaMKIV-mTOR signalling pathway. Activation of PIEZO1 by Yoda1 or gastric bead implantation inhibits ghrelin production, decreases energy intake and induces weight loss in mice. Inhibition of ghrelin production by Piezo1 through the CaMKKII/CaMKIV-mTOR pathway can be recapitulated in a ghrelin-producing cell line mHypoE-42. Our study reveals a mechanical regulation of ghrelin production and appetite by PIEZO1 of X/A-like cells, which suggests a promising target for anti-obesity therapy.

[Superhigh spectral resolution measurement of spectrometer].

The spectral resolution is one of the most important indexes of spectrometer. A new method is put forward for measuring the superhigh spectral resolution based on the Rayleigh criterion and the optical heterodyne, and the uncertainty of this method is analyzed. The spectral resolution of some spectrometer was measured using this method, and the experimental results show that the spectral resolution is higher than 18.9 pm, and the standard uncertainty is 2.3 pm. When showed using wave number, the spectral resolution is higher than 0.078 8 cm(-1), and the standard uncertainty is 0.009 6 cm(-1).

[Endoplasmic reticulum-mediated integrated stress response].

Integrated stress response (ISR) is a high conserved cell adaptive response, which is induced by oxidative stress, deprivation of acid aminos, and endoplasmic reticulum (ER) stress through eukaryotic translation initiator factor 2alpha (eIF2alpha) pathway. Recently, it is reported that protein kinase R-like ER kinase (PERK) , the upstream of eIF2alpha is the key molecule in ISR. PERK regulates protein synthesis, folding, autophagy and apoptosis through cross-talking with inositol-requiring enzyme-1 (IRE1) and activating transcription factor 6 (ATF6), another two signaling pathways in ER stress. We reviewed the factors induced ISR and its signaling pathways, summarized the physiological and pathophysiological role of endoplasmic reticulum-mediated integrated stress response.