Perinatal exposure to bisphenol A impairs cognitive function via the gamma-aminobutyric acid signaling pathway in male rat offspring.

Bisphenol A (BPA) is a common synthetic endocrine disruptor that can be utilized in the fabrication of materials such as polycarbonates and epoxy resins. Numerous studies have linked BPA to learning and memory problems, although the precise mechanism remains unknown. Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the vertebrate central nervous system, and it is intimately related to learning and memory. This study aims to evaluate whether altered cognitive behavior involves the GABA signaling pathway in male offspring of rats exposed to BPA during the prenatal and early postnatal periods. Pregnant rats were orally given BPA (0, 0.04, 0.4, and 4 mg/kg body weight (BW)/day) from the first day of pregnancy to the 21st day of breastfeeding. Three-week-old male rat offspring were selected for an open-field experiment and a new object recognition experiment to evaluate the effect of BPA exposure on cognitive behavior. Furthermore, the role of GABA signaling markers in the cognition affected by BPA was investigated at the molecular level using western blotting and real-time polymerase chain reaction (RT-PCR). The research demonstrated that BPA exposure impacted the behavior and memory of male rat offspring and elevated the expression of glutamic acid decarboxylase 67 (GAD67), GABA type A receptors subunit (GABAARα1), and GABA vesicle transporter (VGAT) in the hippocampus while decreasing the expression levels of GABA transaminase (GABA-T) and GABA transporter 1 (GAT-1). These findings indicate that the alteration in the expression of GABA signaling molecules may be one of the molecular mechanisms by which perinatal exposure to BPA leads to decreased learning and memory in male rat offspring.

Needle-Perc-Assisted Endoscopic Surgery in Treatment with Renal Staghorn Stones: A Prospective Randomized Controlled Study from a Large-Volume Stone Center.

INTRODUCTION: The goal of this study was to evaluate the efficacy and safety of needle-perc-assisted endoscopic surgery (NAES) in the treatment of staghorn renal stones via a single-center prospective randomized controlled study. METHODS: A total of 219 patients with partial or complete staghorn renal stones were prospectively randomized into two groups between January 2020 and April 2022. In group A (n = 112), patients were treated with traditional standard access, multiple if necessary, and in group B (n = 107), only one standard access was made, and needle-perc was assisted to remove the residual stones in the same stage. All procedures were guided under ultrasound totally. Stone size, operating time, blood loss, pain score, complications, and other related characteristics were monitored and analyzed. RESULTS: Procedures were successful in all patients. The baseline characters were similar between the groups. The mean stone size was comparable (4.5 ± 1.4 vs. 4.7 ± 1.7, p = 0.35). The 1-month stone-free status was achieved in 85 patients (75.9%) in group A and 80 (74.8%) patients in group B (p = 0.72). The operation time was shorter in group A than B (75.1 ± 28.1 min vs. 97.2 ± 20.4 min, p = 0.02). A less blood loss (p = 0.01), shorter hospital stay (p = 0.04), lower pain score (p = 0.04), and lower severe complication rates (p = 0.03) were observed in group B. CONCLUSION: NAES reveals better postoperative recurrence compared with traditional multiple tracts method for treating staghorn renal stones. The stone-free rate was comparable between the two groups.

Needle-perc-assisted endoscopic surgery (NAES) for patients with complicated solitary kidney stones: a prospective randomized study from a single center.

PURPOSE: The goal of this study is to compare traditional percutaneous nephrolithotomy (PCNL) and needle-perc-assisted endoscopic surgery (NAES) in the treatment of complicated solitary kidney stones via a single-center randomized controlled prospective study. METHODS: A total of patients with complex (Guy's score II-IV) solitary kidney stones between July 2019 to June 2022 were enrolled in the study. Participants were stratified into two groups: needle-perc-assisted endoscopic surgery group (group A) and traditional PCNL group (group B). All procedures were finished by X-ray free technique. The clinical characteristics and outcomes were analyzed. RESULTS: A total of 90 (44 in Group A and 46 in Group B) patients were finally included in our study. There were no statistically differences in terms of gender, age, body mass index (BMI), stone burden between two groups. The mean operative duration of Group A was significant higher than group B (95.1 ± 21.4 min vs 72.5 ± 29.5 min, p=0.02). The 1-month stone-free rate (SFR) was significant higher in Group A than B (90.9% vs 73.9%, p=0.03). A less hemoglobin drop (p=0.01), shorter postoperative in-hospital day (p=0.04), and lower severe complication (Clavien-Dindo III and above) rates (p=0.03) were observed in Group A. CONCLUSION: For patients with solitary kidney stones, NAES technique provides a higher one-session SFR, a better renal function recovery and compared with traditional PCNL.

Cuticular competing endogenous RNAs regulate insecticide penetration and resistance in a major agricultural pest.

BACKGROUND: The continuously developing pesticide resistance is a great threat to agriculture and human health. Understanding the mechanisms of insecticide resistance is a key step in dealing with the phenomenon. Insect cuticle is recently documented to delay xenobiotic penetration which breaks the previous stereotype that cuticle is useless in insecticide resistance, while the underlying mechanism remains scarce. RESULTS: Here, we find the integument contributes over 40.0% to insecticide resistance via different insecticide delivery strategies in oriental fruit fly. A negative relationship exists between cuticle thickening and insecticide penetration in resistant/susceptible, also in field strains of oriental fruit fly which is a reason for integument-mediated resistance. Our investigations uncover a regulator of insecticide penetration that miR-994 mimic treatment causes cuticle thinning and increases susceptibility to malathion, whereas miR-994 inhibitor results in opposite phenotypes. The target of miR-994 is a most abundant cuticle protein (CPCFC) in resistant/susceptible integument expression profile, which possesses capability of chitin-binding and influences the cuticle thickness-mediated insecticide penetration. Our analyses find an upstream transcriptional regulatory signal of miR-994 cascade, long noncoding RNA (lnc19419), that indirectly upregulates CPCFC in cuticle of the resistant strain by sponging miR-994. Thus, we elucidate the mechanism of cuticular competing endogenous RNAs for regulating insecticide penetration and demonstrate it also exists in field strain of oriental fruit fly. CONCLUSIONS: We unveil a regulatory axis of lnc19419 ~ miR-994 ~ CPCFC on the cuticle thickness that leads to insecticide penetration resistance. These findings indicate that competing endogenous RNAs regulate insecticide resistance by modulating the cuticle thickness and provide insight into the resistance mechanism in insects.

Identification, expression profiles and involvement in insecticides tolerance and detoxification of carboxylesterase genes in Bactrocera dorsalis.

Carboxylesterases (CarEs) are a multifunctional superfamily of enzymes and play an important role in detoxification of various insecticides in insects. The oriental fruit fly, Bactrocera dorsalis, is one of the most destructive agricultural pests and has developed different degrees of resistance to organophosphates in field. However, the involvement of BdCarEs in tolerance or resistance to other alternative insecticides are still unclear. In the present study, 33 BdCarEs genes were identified based on the genome database of B. dorsalis. Phylogenetic analysis demonstrated that they were classified into nine clades, with abundance of α-esterases. Meanwhile, the sequence characterization and the chromosome distribution were also analyzed. The spatiotemporal expression analysis of BdCarEs genes suggested that the diversity of potential function in different physiological processes. With the exception of BdCarE21, all BdCarEs genes responded to at least one insecticide exposure, and BdCarE20 was found to be up-regulated after exposure to all five tested insecticides individually. Eight BdCarEs genes were overexpressed in MR strain when compared to that in SS strain. Subsequently, knockdown the expression of representative BdCarEs genes significantly increased the susceptibility of the oriental fruit fly to corresponding insecticides, which indicated that the tested BdCarEs genes contributed to one or multiple insecticide detoxification. These findings provide valuable insights into the potential role in respond to tolerance or resistance to insecticides with different mode of action, and will facilitate development of efficiency management strategy for B. dorsalis.

Development and validation of an endoplasmic reticulum stress long non-coding RNA signature for the prognosis and immune landscape prediction of patients with lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD), the most common histotype of lung cancer, may have variable prognosis due to molecular variations. This work investigated long non-coding RNA (lncRNA) related to endoplasmic reticulum stress (ERS) to predict the prognosis and immune landscape for LUAD patients. Methods: RNA data and clinical data from 497 LUAD patients were collected in the Cancer Genome Atlas database. Pearson correlation analysis, univariate Cox regression, least absolute shrinkage and selection operator regression analyses, as well as the Kaplan-Meier method, were used to screen for ERS-related lncRNAs associated with prognosis. The risk score model was developed using multivariate Cox analysis to separate patients into high- and low-risk groups and a nomogram was constructed and evaluated. Finally, we explore the potential functions and compared the immune landscapes of two groups. Quantitative real-time PCR was used to verify the expression of these lncRNAs. Results: Five ERS-related lncRNAs were shown to be strongly linked to patients' prognosis. A risk score model was built by using these lncRNAs to categorize patients based on their median risk scores. For LUAD patients, the model was found to be an independent prognostic predictor (p < 0.001). The signature and clinical variables were then used to construct a nomogram. With 3-year and 5-year OS' AUC of 0.725 and 0.740, respectively, the nomogram's prediction performance is excellent. The 5-lncRNA signature was associated with DNA replication, epithelial-mesenchymal transition, and the pathway of cell cycle, P53 signaling. Between the two risk groups, immune responses, immune cells, and immunological checkpoints were found to be considerably different. Conclusion: Overall, our findings indicate that the 5 ERS-related lncRNA signature was an excellent prognostic indicator and helped to predict the immunotherapy response for patients with LUAD.

Is the Supine Position Suitable for Ultrasound-Guided Percutaneous Nephrolithotomy in Patients with Complex Renal Stones?

INTRODUCTION: The aim of the study was to assess the safety and efficacy of ultrasound (US)-guided percutaneous nephrolithotomy (PCNL) for complex renal stones when performed in a modified supine position. METHODS: We retrospectively reviewed the charts of patients who underwent PCNL for complex renal stones at our institution between August 2018 and December 2021. During this time, 188 consecutive patients underwent US-guided PCNL in the prone position (P group, n = 129) or in the flank-free modified supine position (S group, n = 59). Patient demographics and intraoperative and postoperative data were analyzed. RESULTS: Successful renal access was achieved in all patients. The baseline demographics were comparable between the two groups. The numbers of renal access were significantly higher (2.1 ± 0.4 vs. 1.2 ± 0.2, p = 0.002), and the operation time was comparable (79.1 ± 14.6 min vs. 96.2 ± 19.6 min, p = 0.06) between the two groups. The postoperative hospital stay was also shorter in the P group (6.2 ± 1.5 d vs. 10.2 ± 1.7 d, p = 0.008). The postoperative hemoglobin loss was similar between the P and S groups (1.7 ± 0.4 g/dL vs. 1.8 ± 0.3 g/dL, p = 0.12). The stone-free rate was significantly lower in the S group (57.5% vs. 82.7%, p < 0.001). There were no embolization or septic complications. Twelve patients (20.3%) in the S group underwent simultaneous or staged retrograde flexible ureteroscopy to remove residual stones. CONCLUSION: US-guided PCNL in the modified supine position was a safe treatment for complex renal stones. However, the single-session stone clearance rate was not ideal. The supine flank-free position may be unsuitable for US-guided PCNL in patients with complex renal stones according to our preliminary findings.

The relationship between non-alcoholic fatty liver disease and incidence of chronic kidney disease for diabetic and non-diabetic subjects: A meta-analysis.

INTRODUCTION: The prevalence of chronic kidney disease (CKD) rises with age and co-morbid diseases such as liver diseases. OBJECTIVES: The main aim of the current meta-analysis is to assess the relationship between Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease incidence in both diabetic and non-diabetic subjects compared with control. MATERIAL AND METHODS: A systematic literature search of papers published from January 1, 2005, till April 30, 2022, found 19 studies including 1,111,046 subjects; 310,804 were diagnosed with NAFLD, and 800,242 were non-NAFLD. The measured outcome was the incidence of CKD among NAFLD subjects compared to non-NAFLD subjects in diabetic and non-diabetic subjects. Dichotomous analysis methods were used within the random effects model to calculate the odds ratio (OR) with 95% confidence intervals (95% CIs). RESULTS: The incidence of CKD is highly significant in NAFLD subjects compared with controls (OR: 1.95; 95% CI: 1.65-2.31). The diabetic non-NAFLD subjects showed a significantly increased incidence of CKD compared to the non-diabetic subjects with NAFLD (OR: 1.79; 95% CI: 1.35-2.38).. In addition, the incidence of CKD was significantly higher in the NAFLD group compared with the non-NAFLD non-diabetic subjects (OR: 2.52; 95% CI: 1.91-3.32). Diabetes acts as an independent risk factor for CKD, as proven by a significant increase in incidence of diabetic subjects compared to non-diabetic NAFLD subjects (OR: 1.82; 95% CI: 1.15-2.88). CONCLUSION: Non-alcoholic fatty liver disease is significantly related to an increased incidence of CKD, which is significantly higher in diabetic subjects.

Ultrasound-guided renal access and balloon dilation for PCNL in the prone position: results of a multicenter prospective observational study.

PURPOSE: To investigate the safety and efficacy of ultrasound-guided renal access and tract dilation using balloon dilators, as well as to identify suitable patients for this technique. METHODS: Consecutive patients undergoing ultrasound-guided PCNL using balloon dilators between December 2019 and June 2020 in seven large medical centers from China were prospectively enrolled. Demographic and perioperative parameters of the patients were collected. Logistic regression analysis was used to analyze factors that would affect the success rate of tract establishment using ultrasound-guided renal access and balloon dilation. RESULTS: A total of 170 patients were included in this study, among whom, 91.18% of the (155/170) patients had a successful tract establishment under ultrasound guidance on the first attempt. The stone-free rate was 83.5% and postoperative complications occurred in 14 patients (8.23%). In univariate analysis, history of ipsilateral surgery (p = 0.026), and stone diameter (p = 0.01) were significantly associated with tract establishment failure, while a larger width of the target calyx (p = 0.016) and the presence of hydronephrosis (p = 0.001) were significantly associated with a successful tract establishment. In multivariate analysis, only hydronephrosis in target calyx (p = 0.027) was a favorable factor for successful tract establishment, and the history of ipsilateral renal surgery (p = 0.012) was the only independent risk factor for failure of tract establishment. CONCLUSION: It was safe and effective to establish percutaneous renal access with balloon dilation under whole-process ultrasound monitoring during PCNL. Furthermore, patients with a hydronephrotic target calyx and without history of ipsilateral renal surgery were most suited to this technique. Trial registration CHiCTR1800014448.

Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF-κB Signaling Pathway.

Objective: To research the influence of Chinese medicine Jiedu Huayu granules (JDHY) on the immune response and inflammatory response of rats with acute liver failure (ALF) and investigate its related mechanism. Methods: Rats were randomly divided into 4 groups: control group (n = 6) were injected with the same amount of normal saline; ALF group (n = 10) were injected intraperitoneally with D-GaIN (700 mg/kg) and LPS (10 µg/kg); ALF+JDHY group (n = 10) were given JDHY 57.55 g/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose; and ALF+BAY group (n = 10) were given BAY 10 mg/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose. Changes in liver function and coagulation function were examined in rat serum; the pathological varieties of liver tissues were verified by HE staining; immunohistochemistry was utilized to determine the ratio of PCNA and F4/80 in liver tissues; the flow cytometry was applied to determine the ratio of CD4+/CD8+ cells in peripheral blood mononuclear cells (PBMCs); ELISA and qRT-PCR were utilized to check the level of IL-10, IL-6, IL-13, IL-1ß, TNF-α, IFN-γ, and CD163 in serum and liver cells. Western blot was adopted to check the expression of apoptotic protein and expression and NF-κB pathway-related protein expression. Results: JDHY and BAY could decline the expression of AST, ALT, ALP, and TBiL in ALF rat serum significantly (P < 0.01), increase PTA and PLT (P < 0.01), and mitigate liver tissue damage. Besides, JDHY and BAY could reduce the apoptosis and improve the proliferation of the liver cells in rats with ALF; meanwhile, the ratio of CD4+ cells and F4/80 cells was reduced while CD8+ cells were increased (P < 0.01). Further, JDHY and BAY could reduce the level of IFN-γ, IL-6, IL-1ß, and TNF-α while increasing the level of IL-10 and IL-13 (P < 0.01). Additionally, the expression of sCD163 in serum and CD163 expression in liver tissues increased (P < 0.01). The result of western blot confirmed that JDHY could inhibit the phosphorylated expression of NF-κB, IKßα, and IKKß in the ALF rat tissues. Conclusions: JDHY can upregulate the level of CD163/sCD163 by the NF-κB signaling pathway, thereby regulating immune response, inhibiting inflammatory response, and ultimately improving ALF in the rats.

The Clinical Efficacy of Double Plasma Molecular Absorption System Combined with Plasma Exchange in the Treatment of Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis.

Objective: This study aims to investigate the clinical efficacy of plasma exchange in treating acute-on-chronic liver failure (ACLF) through meta-analysis. Method: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched using a computer for all relevant Chinese and English literature from 2000 to 2021 in each database. At the same time, a large number of related papers and materials were manually consulted. Randomized controlled trials of plasma exchange (PE, control group) and combined double plasma molecular absorption system (DPMAS + PE, observation group) for the treatment of ACLF were collected. Meta-analysis was performed with Stata16.0 software. Result: A total of 474 articles were retrieved, and 11 papers were finally included for research after screening. Meta-analysis results showed that the effective rate of treatment in the experimental group was significantly higher than that in the control group. At the same time, the observation group's prothrombin activity (PTA) level was better than that of the control group after treatment. After treatment, there was no significant difference in prothrombin time (PT) and international normalized ratio (INR) between the two groups. In addition, after treatment, the alanine aminotransferase (ALT) level of the observation group was significantly lower than that of the control group. However, TBIL levels and albumin (ALB) levels did not change significantly between the two groups. Regarding blood routine indexes, there were no significant changes in creatinine (Cr) levels and platelet counts (PLT) in the two groups after treatment, but hemoglobin (HGB) levels in the observation group were significantly lower than those in the control group. Conclusion: DPMAS combined with plasma exchange therapy can improve liver function, coagulation function, and blood routine level of ACLF patients and increase the effective rate of treatment. It is an effective treatment for acute-on-chronic liver failure.

Detoxification II Prescription Suppresses the Th-17/IL-17 Inflammatory Axis to Improve the Liver Function of ACLF-Rats via Inactivating the P38MAPK Pathway.

Hepatitis is a metabolic system disease which is a serious challenge to the medical and healthcare system of the world. This study attempted to investigate the therapeutic effect and illustrate the regulation pharmacological mechanism of Detoxification II Prescription on ACLF. In this study, the rats were injected with D-galactosamine to establish ACLF-rat models, and the levels of cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBiL) were measured with the related kits to reflect the liver functions of the rats. The levels of IL-17, IL-6, and IFN-γ in the serums of the rats were detected by qRT-PCR, and the percentages of Th-17 cells in CD4+ cells of the rats were measured by flow cytometry assay. In the results, the increased ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ and decreased ALB and CHE were found in the serums of the ACLF-rats, while Detoxification II Prescription could partly reverse those indexes of the ACLF-rats. Moreover, it was also found that Detoxification II Prescription could inhibit the expression of P38MAPK, and P38MAPK downregulation obviously improved the liver function indexes of the ACLF-rats including the levels of ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ cells. In conclusion, this study suggested that Detoxification II Prescription could suppress the Th-17/IL-17 inflammatory axis to improve the liver function of ACLF-rats via inhibiting the activity of the P38MAPK pathway.

Genome-wide identification of long non-coding RNAs (lncRNAs) associated with malathion resistance in Bactrocera dorsalis.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in the regulation of biological processes and have been identified in many species including insects. However, the association between lncRNAs and pesticide resistance in insect species such as Bactrocera dorsalis is unknown. RESULTS: RNA-seq was performed on malathion resistant (MR1) and susceptible (MS) strains of B. dorsalis and a total of 6171 lncRNAs transcripts were identified. These included 3728 lincRNAs, 653 antisense lncRNAs, 1402 intronic lncRNAs, and 388 sense lncRNAs. A total of 40 and 52 upregulated lncRNAs were found in females and males of the MR1 strain compared to 54 and 49 in the same sexes of the MS strain, respectively. Twenty-seven of these lncRNAs showed the same trend of expression in both females and males in the MR1 strain, in which 15 lncRNAs were upregulated and 12 were downregulated. RT-qPCR results indicated that the differentially expressed lncRNAs were associated with malathion resistance. The lnc15010.10 and lnc3774.2 were highly expressed in the cuticle of the MR1 strain, indicating that these two lncRNAs may be related to malathion resistance. RNAi of lnc3774.2 and a bioassay showed that malathion resistance was possibly influenced by changes in the B. dorsalis cuticle. CONCLUSION: LncRNAs of B. dorsalis potentially related to the malathion resistance were identified. Two lncRNAs appear to influence malathion resistance via modulating the structure, or components, of the cuticle. © 2021 Society of Chemical Industry.

Outcomes of ultrasound-guided percutaneous nephrolithotomy for the treatment of large stones within non-functioning atrophic kidneys.

OBJECTIVES: To evaluate outcomes in patients who underwent total ultrasound-guided percutaneous nephrolithotomy for the management of large stones (>2 cm) within non-functioning atrophic kidneys, and to identify risk factors associated with postoperative persistence of urinary tract infection symptoms in such patients. METHODS: Between December 2014 and May 2019, 56 patients with large stones within non-functioning atrophic kidneys were treated at Beijing Tsinghua Changgung Hospital, Beijing, China, with total ultrasound-guided percutaneous nephrolithotomy. Factors including age, sex, previous medical history, stone burden, stone composition, stone-free rate, complication rate and postoperative urinary tract infection symptoms were retrospectively evaluated. Uni- and multivariate analyses were carried out to identify risk factors that predict persistence of urinary tract infection symptoms after percutaneous nephrolithotomy in such patients. RESULTS: The final stone-free rate after auxiliary treatments was 87.5%. The overall complication rate was 17.9%. After a median follow-up period of 12 months (range 6-40 months), three patients (5.4%) ultimately underwent nephrectomy. A total of 44 patients (78.6%) had no symptoms of urinary tract infection during follow up, whereas 63.6% of patients with diabetes continued to show persistent urinary tract infection symptoms at the latest follow up. Five patients (8.9%) showed improved total renal function, while most patients (83.9%) showed a stable estimated glomerular filtration rate. Diabetes was the only factor showing statistical significance in both univariate and multivariate analyses that predicted persistence of urinary tract infection symptoms after treatment with percutaneous nephrolithotomy. CONCLUSIONS: Ultrasound-guided percutaneous nephrolithotomy is a safe and feasible procedure that can be carried out in patients with large stones within non-functioning atrophic kidneys. However, for such patients with diabetes, percutaneous nephrolithotomy is not recommended.

Percutaneous Nephrolithotomy Under X-Ray-Free Technique in Upper Urinary Stone Patients with Autosomal Dominant Polycystic Kidney Disease: Experience from a Large-Volume Stone Management Center.

Objectives: To present our large single-center experience in the management of autosomal dominant polycystic kidney disease (ADPKD) with total ultrasound (US)-guided percutaneous nephrolithotomy (PNL) and to evaluate the role of PNL under US in these patients. Patients and Methods: We retrospectively reviewed the charts of patients with ADPKD who underwent PNL from August 2011 to December 2019. A total of 56 patients were included in this study; all procedures were completed by the total US-guided technique. Demographic characteristics, operative parameters, and postoperative data were collected and analyzed. Results: Effective renal access was achieved in all patients. The mean stone size was 3.1 cm (range 1.7-6.5 cm). The initial stone-free rate was 70.6% (36/51); five patients underwent second-look PNL to remove residual stones. The other patients underwent oral medication therapy. No severe intraoperative complications occurred; one patient received selective embolization for bleeding on the contralateral side and one patient needed percutaneous drainage for perinephric abscess. Clavien I or II complications were seen in nine patients. Renal function was improved or stable in most patients; the condition of only one patient deteriorated after surgery. Conclusion: Total US-guided PNL is a safe and efficient treatment for kidney stones in patients with ADPKD; perioperative renal function was not adversely affected and complications were acceptable compared with patients in the general population.

A glutathione S-transferase (BdGSTd9) participates in malathion resistance via directly depleting malathion and its toxic oxide malaoxon in Bactrocera dorsalis (Hendel).

BACKGROUND: The oriental fruit fly, Bactrocera dorsalis (Hendel), is a widespread agricultural pest that has evolved resistance to many commonly used insecticides including malathion. Glutathione S-transferases (GSTs) are multifunctional enzymes that metabolize insecticides directly or indirectly. The specific mechanism used by GSTs to confer malathion resistance in B. dorsalis is unclear. RESULTS: BdGSTd9 was identified from B. dorsalis and was expressed at twice the level in a malathion-resistant strain (MR) than in a susceptible strain (MS). By using RNAi of BdGSTd9, the toxicity of malathion against MR was increased. Protein modelling and docking of BdGSTd9 with malathion and malaoxon indicated key amino acid residues for direct binding in the active site. In vitro assays with engineered Sf9 cells overexpressing BdGSTd9 demonstrated lower cytotoxicity of malathion. High performance liquid chromatography (HPLC) analysis indicated that malathion could be broken down significantly by BdGSTd9, and it also could deplete the malathion metabolite malaoxon, which possesses a higher toxicity to B. dorsalis. Taken together, the BdGSTd9 of B. dorsalis could not only deplete malathion, but also react with malaoxon and therefore enhance malathion resistance. CONCLUSION: BdGSTd9 is a component of malathion resistance in B. dorsalis. It acts by depleting both malathion and malaoxon. © 2020 Society of Chemical Industry.

Identification of a novel lncRNA GABPB1-IT1 that is downregulated and predicts a poor prognosis in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Previous studies have demonstrated that long non-coding RNAs (lncRNAs) serve important roles in diverse biological processes. However, the molecular function and prognostic value of the majority of lncRNAs in non-small cell lung cancer (NSCLC) remain unknown. The present study investigated the expression of the lncRNA GABPB1 intronic transcript (GABPB1-IT1) in NSCLC tissues using publicly available databases. Subsequently, protein-protein interaction (PPI) and co-expression networks were constructed to identify key targets of lncRNA GABPB1-IT1. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the potential roles of lncRNA GABPB1-IT1. The current study identified that the expression of GABPB1-IT1 was significantly downregulated in NSCLC samples compared with normal samples. Furthermore, the expression levels of GABPB1-IT1 were lower in high grade NSCLC samples compared with low grade NSCLC samples. Additionally, overexpression of GABPB1-IT1 in cancer samples was associated with improved survival of patients with NSCLC. GABPB1-IT1 was revealed to be involved in the regulation of cell cycle-associated biological processes, including sister chromatid cohesion, mitotic nuclear division, DNA replication, chromosome segregation, G1/S transition of mitotic cell cycle, mitotic cytokinesis and cell division. Finally, a GABPB1-IT1-associated protein-protein interaction network was constructed for NSCLC. To the best of our knowledge, the present study was the first to demonstrate that GABPB1-IT1 is associated with the prognosis of NSCLC. The current study provides useful information to assist with the investigation of potential candidate biomarkers for diagnosis, prognosis and drug targets for NSCLC.

Cdh1-Mediated Metabolic Switch from Pentose Phosphate Pathway to Glycolysis Contributes to Sevoflurane-Induced Neuronal Apoptosis in Developing Brain.

Cdh1 is a regulatory subunit of the anaphase promoting complex/cyclosome (APC/C), known to be involved in regulating neuronal survival. The role of Cdh1 in volatile anesthetics-induced neuronal apoptosis in the developing brain is unknown. In this study, we used postnatal day 7 (P7) and day 21 (P21) mice exposed to 2.3% sevoflurane for 6 h to investigate at which age and duration of exposure sevoflurane affects the expression of Cdh1 and glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and that of the pentose phosphate pathway (PPP) enzyme, glucose-6-phosphate dehydrogenase (G6PD). Furthermore, we tested whether the cyclin-dependent kinases (cdks) inhibitor roscovatine could counteract the effects caused by exposure to sevoflurane. Finally, we applied the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3-PO), G6PD inhibitor dehydroepiandrosterone (DHEA), and exogenous reduced glutathione to examine the contribution of the glycolysis pathway and PPP to sevoflurane-induced neuroapoptosis. We found that prolonged sevoflurane anesthesia significantly reduces the Cdh1 level in P7 mice compared to in the P21 ones; moreover, the decrease in Cdh1 level results in a switch in glucose metabolism from the PPP to neuronal glycolysis. This leads to an imbalance between reactive oxygen species production and reduced glutathione level in the developing brain, which is more susceptible to oxidative stress. As a result, sevoflurane induces neuroapoptosis through Cdh1-mediated glucose metabolism reprogramming. Our study demonstrates a critical role of Cdh1 in sevoflurane-induced neuroapoptosis by shifting PPP to the glycolytic pathway in the developing brain. These findings suggest that Cdh1 may be a novel target for preventing volatile anesthetics-induced neurotoxicity and memory impairment.

Long-term outcomes of ultrasound-guided percutaneous nephrolithotomy in patients with solitary kidneys: a single-center experience.

PURPOSE: To report our experience with total ultrasound-guided percutaneous nephrolithotomy (PCNL) in the management of patients with solitary kidney, and evaluate the safety and feasibility of this technique. MATERIALS AND METHODS: Between October 2014 and December 2016, 48 patients with solitary kidneys underwent total ultrasound-guided PCNL at our institution. Stone-free rate (SFR), auxiliary procedures, and complications were recorded. Changes in renal function were evaluated by comparing preoperative and postoperative estimated glomerular filtration rates (eGFRs). Perioperative factors that may affect renal function were analyzed to define factors predicting renal function improvement on long-term follow-up. Of 48 patients, 44 were followed at least 6 months, whereas four patients were lost to follow-up. RESULTS: Among all patients, staghorn calculi were found in 18 (37.5%) patients. 14 (29.2%) patients required a two-stage PCNL. Struvite was found in six (12.5%) patients. Complications were reported in eight (16.7%) patients. Severe bleeding was noticed in three patients; no angioembolization was required. After a median follow-up of 12 (6-26) months, the final SFR was 81.8% after auxiliary treatments. There was a significant improvement of eGFR from 53.9 ± 24.0 to 61.3 ± 25.4 mL/min/1.73 m2 (P < 0.01). Renal function was stable, improved and worse in 65.9% (n = 29), 27.3% (n = 12), and 6.8% (n = 3) of patients, respectively, compared with preoperative levels. CONCLUSIONS: Ultrasound-guided PCNL is a safe and feasible procedure with an acceptably low complication rate in patients with solitary kidneys. At long-term follow-up, the renal function in more than 90% of the patients with solitary kidneys can be improved or stabilized after ultrasound-guided PCNL.