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Yong Li,1,* Sheng-Chun Fang,2,* Lan Zhou,1 Xue-Mei Mo,3 Hao-Dong Guo,3 Yan-Bo Deng,3 Hong-Hao Yu,1 Wei-Yi Gong3 1College of Biotechnology, Guilin Medical University, Guilin, Guangxi, 541100, People’s Republic of China; 2Department of Anesthesiology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430015, People’s Republic of China; 3Department of Pain Management, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Hao Yu, College of Biotechnology, Guilin Medical University, Guilin, Guangxi, 541100, People’s Republic of China, Email geneyhh@126.com Wei-Yi Gong, Department of Pain Management, Affiliated Hospital of Guilin Medical University, Guilin, 541000, Guangxi, People’s Republic of China, Email 942261597@qq.comBackground: Neuropathic pain (NP) after spinal cord injury (SCI-evoked NP) is clinically challenging; the underlying mechanisms are not fully understood, leading to a lack of promising treatment options. NP occurs in only a subset of patients with SCI. The injured spinal cord exhibits a series of histopathological changes, and the complement system has been shown to play an important role in these processes. In addition, NMDA receptor subunit 2B (NR2B) is involved in the development and maintenance of NP. This preliminary study was performed to investigate the correlations of the complement receptor 3/complement component 3 (CR3/C3) pathway and NR2B with SCI-evoked NP.Methods: A trauma-induced SCI animal model was established and SCI-evoked NP was evaluated by behavioural analysis. Transcriptome analysis was performed to identify genes in the CR3/C3 pathway related to synaptic modification, while the expression and distribution of NR2B in the injured spinal cord, and the relation to NP, were examined by immunohistochemical analysis.Results: Nine of seventeen SCI rats (52.9%) developed NP. C3 mRNA expression was significantly decreased in SCI-evoked NP rats and significantly increased in the non-NP SCI rats. C1q mRNA and CR3 mRNA expression were significantly increased in all SCI rats, but higher levels of expression were observed in the non-NP SCI rats. NR2B mRNA expression was significantly increased in the SCI-evoked NP rats and significantly decreased in the non-NP SCI rats. In addition, significantly elevated expression of NR2B-positive cells was seen in lamina II of the superficial dorsal horn in SCI-evoked NP rats in comparison with non-NP SCI rats.Conclusion: NP occurred in only a subset of SCI rats, and the CR3/C3 pathway and NR2B were involved in SCI-evoked NP. Further studies are required to determine the mechanisms underlying the SCI-evoked NP associated with the CR3/C3 pathway and NR2B.Keywords: spinal cord injury, neuropathic pain, complement receptor 3, complement component 3, NMDA receptor 2B subunit

Background: Postoperative pain management remains a significant challenge for patients undergoing posterior urethroplasty (PU). In a previous study, we proposed a novel technique of combined pudendal nerve (PN) and spermatic cord (SC) block to manage pain after PU. The present trial was conducted to test the hypothesis that this technique is effective for pain control after PU and provides longer-lasting analgesia than caudal epidural block (CB)., Methods: Sixty patients undergoing PU were randomized into two groups: Group NB received combined PN and SC block, and Group CB received CB. General anesthesia with a laryngeal mask was performed. The primary outcome was the postoperative analgesic duration, and the secondary outcomes included the Numeric Rating Scale (NRS) scores for pain and the number of patients with different motor scores of the lower limb at 3, 6, 12, and 24 h postoperatively., Results: Two patients in Group CB were withdrawn due to block failure. The postoperative analgesic duration was statistically longer in Group NB compared with Group CB (mean difference [95% confidence interval], 115.78 min [17.80, 213.75]; P = 0.021). The NRS scores for pain at 12 and 24 h after surgery were statistically lower in Group NB compared with Group CB. Group NB had statistically more patients with motor score 0 at 3 h postoperatively than Group CB., Conclusions: PN combined with SC block is an effective technique for postoperative analgesia in PU. This technique can achieve a longer duration of analgesia and lower pain scores, especially 12 h after surgery, than a CB., Trial Registration: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2100042971, registration date on 2/2/2021)., (© 2024. The Author(s).)

Inositol-requiring enzyme 1 (IRE1), a mediator of the unfolded protein response, shows the highest degree of evolutionary conservation. Vertebrates express two IRE1 paralogs: IRE1α, which is universally expressed and IRE1β, which shows specific expression within mucus secreted cells in respiratory and gastrointestinal tracts. The biological properties and regulation of the two IRE1 duplicates show evolutionary differences. As recently suggested, IRE1β-deficient mice display impairment in secreted protein expression and mucosal homeostasis. Abnormal changes in IRE1β caused by external and internal factors can disrupt mucosal homeostasis and further lead to respiratory and gastrointestinal diseases. Here, we highlight the physiological functions of IRE1β in the respiratory and gastrointestinal tracts in response to environmental microbes, viruses, toxins, and food components., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Objective: To describe the prevalence of food allergy among children aged 0-5 years in China and to explore related influencing factors. Methods: Multistage stratified random sampling method was used to collect data from 275 surveillance sites of the China National Nutrition and Health Survey of Chinese children and lactating mothers programs in 31 provinces (autonomous regions and municipalities) of China in 2016-2017. A total of 70 107 participants aged 0-5 years were included in this study. The study collected information of participants' demographic characteristics and food allergies by face-to-face questionnaire. The prevalence of food allergy was analyzed, using the complex data weighting method. The logistic regression models were used to analyze the influencing factors related to food allergy. Results: The overall prevalence of self-reported food allergy among children aged 0-5 years was 4.81%. Prevalence rates in infants aged 0-5 months, and 6-23 months and preschool children aged 2-5 years were 0.81%, 4.68% and 5.26%, respectively. The results of logistic analysis showed that there was a significantly positive correlation between factors including children from 6 months to 5 years old, urban area, southwest area, first-born, mothers with college education or above, and the prevalence of food allergy in children. Shrimp, poultry eggs, crab shellfish, fruit, milk and fish appeared the common allergic foods in children aged 0-5 years, with prevalence rates of self-reported food allergy as 1.55%, 1.25%, 0.99%, 0.97%, 0.87% and 0.86%, respectively. The proportion of single food allergy in children with allergies was 69.85%. Conclusions: Among children aged 0-5 years, the prevalence of self-reported food allergy increases with age, in China. Foods that is prone to allergies include fish, shrimp, crab, shellfish, poultry eggs, milk and fruits, etc . Most allergies were only caused by single food in children, under observation.

This study aimed to compare the postoperative analgesic efficacy and motor recovery of a novel lumbar plexus block (LPB) with that of a femoral nerve block (FNB) after total knee arthroplasty (TKA). Forty patients who underwent TKA were randomised equally into an lumbar plexus and sciatic nerve (LS) group (receiving novel LPB) and an femoral and sciatic nerves (FS) group (receiving FNB). The assessed variables were the onset time of pain, time to the first analgesic request, pain scores, motor block at 6, 12, and 24 h after TKA, and the number of patients receiving successful blockade for each branch of the lumbar plexus. In the LS group, the femoral, lateral femoral cutaneous, genitofemoral, iliohypogastric, ilioinguinal, and obturator nerves were blocked in 18, 20, 16, 18, 15, and 19 patients. Compared to the FS group, the LS group had a significantly shorter onset time of pain and time to the first analgesic request, a significantly larger total postoperative dose of sufentanil, significantly higher numeric rating scale scores for both rest and dynamic pain at 6, 12, and 24 h, and faster motor recovery. Novel ultrasound-guided LPB has a high blocking success rate and provides inferior postoperative analgesia, but faster motor recovery after TKA than FNB., Competing Interests: Conflict of interest: The authors declare that they have no known conflict of interest or personal relationships that could have appeared to influence the work reported in this article., (© 2024 the author(s), published by De Gruyter.)

Ubiquitin fold modifier 1 is a small ubiquitin-like protein modifier that is essential for embryonic development of metazoans. Although UFMylation has been connected to endoplasmic reticulum homeostasis, the underlying mechanisms and the relevant cellular targets are largely unknown. Here, we show that HRD1, a ubiquitin ligase of ER-associated protein degradation (ERAD), is a novel substrate of UFM1 conjugation. HRD1 interacts with UFMylation components UFL1 and DDRGK1 and is UFMylated at Lys610 residue. In UFL1-depleted cells, the stability of HRD1 is increased and its ubiquitination modification is reduced. In the event of ER stress, the UFMylation and ubiquitination modification of HRD1 is gradually inhibited over time. Alteration of HRD1 Lys610 residue to arginine impairs its ability to degrade unfolded or misfolded proteins to disturb protein processing in ER. These results suggest that UFMylation of HRD1 facilitates ERAD function to maintain ER homeostasis., (© 2023 Federation of American Societies for Experimental Biology.)

Objective: To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-β1 (TGF-β1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs)., Methods: The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-β1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016., Results: LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-II (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of -8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1., Conclusion: RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Developing adequate regional anaesthesia for knee surgeries without affecting lower limb mobilization is crucial to perioperative analgesia. However, reports in this regard are limited. We proposed a technique for ultrasound-guided peripatellar plexus (PP) block. Compared with the femoral nerve (FN) block, we hypothesized that this technique would provide a noninferior block duration and a complete cutaneous sensory block in the peripatellar region without affecting lower limb mobilization. An investigation was conducted to verify our hypothesis in cadavers and volunteers., Methods: The study was designed in two parts. First, eight cadaveric lower limbs were dissected to verify the feasibility of PP block after methylene blue injection under ultrasound. Second, using a noninferiority study design, 50 healthy volunteers were randomized to receive either a PP block (PP group) or an FN block (FN group). The primary outcome was the duration of peripatellar cutaneous sensory block, with the prespecified noninferiority margin of -3.08 h; the secondary outcome was the area of peripatellar cutaneous sensory block; in addition, the number of complete anaesthesias of the incision line for total knee arthroplasty and the Bromage score 30 min after block were recorded., Results: The PP was successfully dyed, whereas the FN and saphenous nerve were unstained in all cadaveric limbs. The mean difference of the block duration between the two groups was - 1.24 (95% CI, -2.81 - 0.33) h, and the lower boundary of the two-sided 95% CI was higher than the prespecified noninferiority margin (P noninferiority = 0.023), confirming the noninferiority of our technique over FN block. The cutaneous sensory loss covered the entire peripatellar region in the PP group. PP block achieved complete anaesthesia of the incision line used for total knee arthroplasty and a Bromage score of 0 in 25 volunteers, which differed significantly from that of volunteers who underwent FN block., Conclusion: Ultrasound-guided PP block is a feasible technique. Compared with FN block, PP block provides noninferior block duration and complete blocking of the peripatellar region without affecting lower limb mobilization., Trial Registration: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2000041547, registration date 28/12/2020)., (© 2022. The Author(s).)

The renal medulla is a key site for the regulation of renal sodium excretion. However, the molecular mechanism remains unclear. Cyclooxygenase 2 (COX2) is specifically expressed in the renal medulla and contributes to the maintenance of the electrolyte/water balance in the body. Hypoxia-inducible factors (HIFs) have also been found to be expressed in the renal medulla, probably owing to the hypoxic conditions in the renal medulla. This study was designed to test the effects of HIF activation on renal sodium handling and renal medullary COX2 expression. Our data showed that HIF activation by the prolyl hydroxylase inhibitor (PHI) FG4592 enhanced natriuresis in mice challenged with a high-salt diet. In addition, FG4592 upregulated the expression of COX2 in the renal medulla. An in vitro study further supported the finding that HIF can induce the expression of COX2 and that this induction is mediated through direct binding to the promoter region of the Cox2 gene, facilitating its transcription. In addition, the COX2 inhibitor celecoxib diminished the natriuretic effect of FG4592. Together, these results suggest that HIF activation promotes sodium excretion through upregulation of COX2 in the renal medulla and therefore maintains sodium homeostasis in the body., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The relieving role of dezocine in pain after surgery was previously reported, while the potential mechanism was not completely clear. Therefore, the current research probed into the regulatory mechanism of dezocine in pain after surgery. A postoperative pain model was established by performing plantar incision surgery on the juvenile Sprague-Dawley rats. After the rats were treated with dezocine or SC79 (Akt1 activator), the paw withdrawal threshold and paw withdrawal latency of rats were detected to evaluate the mechanical allodynia and thermal hyperalgesia. After the plantar tissue, dorsal root ganglions, and spinal cord of rats were collected, the expressions of Akt1, p-Akt1, GSK-3β, and p-GSK-3β in the tissues were determined by western blot to evaluate the activation state of the Akt1/GSK-3β pathway. After surgery, the paw withdrawal threshold and paw withdrawal latency of rats were lessened, whereas the ratios of p-Akt1/Akt1 and p-GSK-3β/GSK-3β were augmented in rat plantar tissue, dorsal root ganglions, and spinal cord. After treatment with dezocine alone, the paw withdrawal threshold and paw withdrawal latency of postoperative rats were elevated, but ratios of p-Akt1/Akt1 and p-GSK-3β/GSK-3β were reduced. After co-treatment with dezocine and SC79, SC79 reversed the effects of dezocine on elevating the paw withdrawal threshold and paw withdrawal latency, and reducing the ratios of p-Akt1/Akt1 and p-GSK-3β/GSK-3β in postoperative rats. Dezocine ameliorated the postoperative hyperalgesia in rats via repressing the hyper-action of Akt1/GSK-3β pathway., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sleep deprivation (SD) has many deleterious health effects, including cognitive decline, work ability decline, inadequate alertness, etc. Neuroinflammation plays an important role in sleep deprivation. However, the underlying mechanism is still unclear., Methods: In the present study, we detected the activation of microglia and apoptosis of nerve cells in sleep deprivation (SD) mice model using IHC, HE staining and TUNEL apoptosis assay. RT-PCR array data were used to detect the expression of inflammatory bodies in hippocampal CA1 region after sleep deprivation, to explore how NLRP3 inflammasome regulates neuronal apoptosis and how specific signaling pathways are involved in SD-induced activation of NLRP3/pyrosis axis., Results: We found the number of microglia significantly increased in SD mice, while this effect was blocked by sleep recovery. RT-PCR array data suggested that NLRP3 inflammasome, but not other inflammasomes, was obviously increased in hippocampus CA1 region after sleep deprivation. Mechanistically, we found that NLRP3 mediated the pyroptosis of neurocyte through GSDMD-dependent way , and P38 and ERK-MAPK signaling pathway is involved in SD-induced activation of NLRP3/pyroptosis axis. All these results suggested that MAPK/NLRP3 axis mediated SD-induced pyroptosis., Conclusion: NLRP3 plays an important role in SD-induced neuroinflammation. Thus, NLRP3 inflammasome is expected to be a potential therapeutic target for SD-induced neuroinflammation., Competing Interests: The authors declare there are no competing interests., (©2021 Fan et al.)

Alport syndrome (AS) is an inherited kidney disease caused by defects in type IV collagen, which is characterized by hematuria, progressive nephritis or end-stage renal disease (ESRD), hearing loss, and occasionally ocular lesions. Approximately 80% of AS cases are caused by X-linked mutations in the COL4A5 gene. This study explored novel deletion and missense mutations in COL4A5 responsible for renal disorder in two Han Chinese families. In pedigree 1, the five male patients all had ESRD at a young age, while the affected female members only presented with microscopic hematuria. Whole exome sequencing and Sanger sequencing identified a novel frameshift deletion mutation (c.422&#95;428del, p.Leu142Valfs∗11) in exon 7 of COL4A5 . In pedigree 2, the 16-year-old male proband had elevated serum creatinine (309  μ mol/L) without extrarenal manifestations, while his mother only manifested with hematuria. A missense mutation (c.476G>T, p.Gly159Val) was found in exon 9 of the COL4A5 gene. Neither of these mutations was present in the Exome Variant Server of the NHLBI-ESP database, nor was it found in the ExAC or 1000 Genomes databases. Through the literature review, it was found that male Chinese patients with X-linked AS carried COL4A5 deletion or missense mutations had a more severe phenotype than female patients, particularly in proteinuria and impaired renal function. Compared to male patients with missense mutations, patients in whom deletion mutations were found were more likely to progress to ESRD (15.4% vs. 36.0%, P = 0.041). This study identified two novel COL4A5 mutations in Chinese families with X-linked AS, expanded the mutational spectrum of the COL4A5 gene, and presented findings that are significant for the screening and genetic diagnosis of AS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wen-yu Gong et al.)

Objective: To investigate the effects of phytic acid derived bioactive P 2 O 5 -SiO 2 -CaO gel-glasses (PSC) on the proliferation, differentiation and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro ., Methods: HUVECs were cultured in PSC extracts, which were prepared with endothelial cell medium (ECM) at a gradient concentration of 0.01, 0.1, 1 and 2 g/L. Cells cultured in ECM were used as the control. The effect of PSC on HUVECs proliferation was assessed on the 1st, 3rd, 5th, 7th and 10th days with (4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide assay (MTT), and the optimum PSC concentration for HUVECs proliferation was used in the following experiments. The subsequent experiments were divided into two groups. The experimental group used PSC extracts to culture HUVECs (PSC group) and the control group used ECM to culture HUVECs (ECM group). Gene expression of angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), was detected on the 2nd, 4th and 7th days by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). The morphology and number of tubules formation were observed at the 4th and 10th hours. Image J software was used for counting and quantitative analysis., Results: The results of MTT assay showed that 0.1 g/L PSC group had the most significant effect on promoting HUVECs proliferation. The optical density values of 0.1 g/L PSC group on the 5th and 7th days were significantly higher than those of the other PSC groups and the control group ( P < 0.05). The result of real-time RT-PCR showed that 0.1 g/L PSC extract up-regulated the mRNA expression of VEGF and bFGF significantly ( P < 0.05). On the 4th day, the gene expressions of VEGF and bFGF in PSC group were 1.59 and 1.45 times higher than those in ECM group respectively, and on the 7th day, the gene levels of VEGF and bFGF in PSC group were 1.98 and 1.37 times higher than those in ECM group respectively. The tubule formation assay showed that the maturity and density of the tubules in 0.1 g/L PSC group was much better than that in the ECM group at the 10th hour. The quantitative analysis by Image J indicated that the tubules number in PSC group (29.63±2.29) was higher than in the ECM group (20.13±2.36), with statistical significance ( P < 0.05)., Conclusion: PSC showed significant promoting effects on HUVECs' proliferation, differentiation and angiogenesis in vitro .

Objective: To evaluate the clinical efficacy and influence factors of direct pulp capping using a bioactive ceramic in mature permanent teeth with carious pulp exposure, in order to explore the feasibility and indications of vital pulp therapy for such teeth. Methods: From January 2016 to September 2017, 57 patients (57 teeth) with carious pulp exposure in mature permanent teeth were selected from the Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology. All the teeth were preoperatively diagnosed as deep caries with normal pulp or reversible pulpitis. After rubber dam isolation, all the carious dentin was removed and the exposed pulp tissue was observed under microscope. Hemostasis should be achieved within 3 min by using 2.5% sodium hypochlorite cotton pellets with a gently press. A resin composite restoration was performed immediately or 2 weeks later after direct pulp capping by using a bioceramic material (iRoot BP Plus). The patients were re-examined 12 to 50 months after operation (average 30 months) and the outcomes were evaluated by symptoms, clinical examination and X-ray. Kaplan-Meier survival analysis was used to calculate the success rate and influence factors were analyzed by Log-Rank test. Results: Totally 50 patients [age (32±13) years old (13-68 years old), 12 males and 38 females] received the follow-up examination more than one year. The overall success rate was 90% (45/50) and the success rates at 1 year, 2 years, 3 years and more were 98%, 89% and 81%, respectively. Age, gender, symptom, tooth and cavity type, pulpal exposure size and coronal restoration material had no significant correlations with the treatment outcome ( P> 0.05). Conclusions: Direct pulp capping of mature permanent teeth with carious pulp exposure by using iRoot BP Plus might have high success rate. There's no significant correlations between the major clinical factors and the treatment outcome.

Background: About 18% to 40% of the survivors have moderate to severe neurological dysfunction. At present, studies on mean arterial pressure (MAP) and neurological function of patients survived after cardiopulmonary resuscitation (CPR) are limited and conflicted., Hypothesis: The higher the MAP of the patient who survived after CPR, the better the neurological function., Method: A retrospective cohort study was conducted to detect the relationship between MAP and the neurological function of patients who survived after CPR by univariate analysis, multivariate regression analysis, and subgroup analysis., Results: From January 2007 to December 2015, a total of 290 cases met the inclusion criteria and were enrolled in this study. The univariate analysis showed that MAP was associated with the neurological function of patients who survived after CPR; its OR value was 1.03 (1.01, 1.04). The multi-factor regression analysis also showed that MAP was associated with the neurological function of patients survived after CPR in the four models, the adjusted OR value of the four models were 1.021 (1.008, 1.035); 1.028 (1.013, 1.043); 1.027 (1.012, 1.043); and 1.029 (1.014, 1.044), respectively. The subgroups analyses showed that when 65 mm Hg ≤ MAP<100 mm Hg and when patients with targeted temperature management or without extracorporeal membrane oxygenation, with the increase of MAP, the better neurological function of patients survived after CPR., Conclusion: This study found that the higher MAP, the better the neurological function of patients who survived after CPR. At the same time, the maintenance of MAP at 65 to 100 mm Hg would improve the neurological function of patients who survived after CPR., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: To study the effect of bioactive glass (BG) on the dentin bond strength and the microleakage of hybrid layer., Methods: In the study, 30 dentin planes were prepared from the third molars with no caries and equally assigned to the control group, BG group, and sodium trimetaphosphate (STMP)-polyacrylic acid (PAA)-BG group (S-P-BG group), randomly. After etched with 35% phosphoric acid, the dentin planes of BG group were pretreated with 0.5 g/L BG, and the dentin planes of S-P-BG group were pretreated with 5% STMP, 5% PAA and 0.5 g/L BG. No additional pretreatment was done to the dentin planes of control group. Then the dentin planes were bonded using 3M Single Bond 2 adhesive to 3M Z350XT composite resin, and cut into 0.9 mm×0.9 mm column samples, which were stored at 37 ℃ artificial saliva (AS). After 24 hours, 1 month, and 3 months, the microtensile bond strength test was performed. The data were analyzed using one-way ANOVA and LSD method. The morphology of the bond fracture interface was observed with scanning electron microscope. Other 27 teeth were collected and the enamel layer and roots cut off, with the pulp chamber exposed. 0.1% rhodamine B was added to the 3M Single Bond 2 adhesive, and then the adhesive was applied to complete the bonding procedures as above. The teeth were stored in 37 ℃ AS for 24 hours, 1 month, 3 months, and then 0.1% sodium fluorescein solution was placed in the chambers and stained for 1 hour. Confocal laser scanning microscopy was used to observe the interface morphology and microleakage of the hybrid layer., Results: At the end of 24 hours and 1 month, there was no significant difference in the microtensile bond strength among the three groups ( P >0.05). After 3 months of soaking, the S-P-BG group [(36.91±7.07) MPa] had significantly higher microtensile bond strength than the control group [(32.73±8.06) MPa] ( P =0.026); For the control group and the BG group, the microtensile bond strength significantly decreased at the end of 3 months compared with 24 hours (control group: P =0.017, BG group: P =0.01); The microtensile bond strength of S-P-BG group af the end of 3 months had no significant difference in compared with 24 hours [(37.99±7.98) MPa] ( P >0.05). Observation of the fracture surface at the 24 hours showed no obvious mineralization in all the three groups. After 1 and 3 months, mineral formation was observed in BG group and S-P-BG group, and no obvious collagen exposure was observed in S-P-BG group. Confocal laser scanning microscopy revealed no obvious differences in the morphology and quantity of the resin tag in the control group, BG group and S-P-BG group. At the end of 24 hours, leakage was found in all the three groups. The microleakage of the control group increased at the end of 3 months, while the microleakage of the BG and S-P-BG groups decreased., Conclusion: BG pretreatment of dentin bonding interface can induce mineralization at the bonding interface and reduce the microleakage of the hybrid layer; pretreating the dentin bonding interface with STMP, PAA and BG may enhance the maintaining of the dentin bonding durability.

Background: "Neuronal precursor cell expressed developmentally down-regulated 4-like" (NEDD4L) is considered a candidate gene for hypertension-both functionally and genetically-through the regulation of the ubiquitination of the epithelial sodium channel (ENaC). This study explores the relationship between genetic variation in NEDD4L and hypertension with chronic kidney disease (CKD) in the southeastern Han Chinese population., Methods: We recruited 623 CKD patients and measured ambulatory blood pressure monitoring (ABPM), and the rs4149601 and rs2288774 polymorphisms in NEDD4L were genotyped using quantitative polymerase chain reaction., Results: For rs4149601, significant differences in genotype frequencies in an additive model (GG vs. GA vs. AA) were observed between normotensive patients and hypertensive patients when hypertension was classified into ambulatory hypertension, clinical hypertension, and ambulatory systolic hypertension (P = 0.038, 0.005, and 0.006, respectively). In a recessive model (GG + GA vs. AA), the frequency of the AA genotype of rs4149601 in the hypertension groups was all higher than that in the normotensive groups. The genotype distribution of rs2288774 did not differ significantly between the normotensive and hypertensive patients. In both the full cohort and the propensity score matching (PSM) cohort, the AA genotype of rs4149601 (compared with the GG + GA genotype group) was independently correlated with ambulatory hypertension, clinical hypertension, and ambulatory systolic hypertension by multivariate logistic regression analysis., Conclusions: The present study indicates that the AA genotype of rs4149601 associates with hypertension in CKD. Consequently, the rs4149601 A allele might be a risk factor for hypertension with CKD., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives and importance: Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm with a high prevalence (>80%) of mutations in the colony-stimulating factor 3 receptor (CSF3R); these mutations activate the receptor, leading to the proliferation of neutrophils that are a hallmark of CNL. Clinical presentation: We present a male patient who presented peripheral blood leukocytosis. On the basis of his morphological appearances and molecular findings he was determined to have a diagnosis of chronic neutrophilic leukemia. At a follow-up at 7 months, in addition to the CSF3R c.2373G > A (p.W791*) truncated mutation, another CSF3R mutation appeared as c.1853C > T(p.T618I). Discussion and conclusion: We present the first patient with a diagnosis of chronic neutrophilic leukemia with a c.2373G > A (p.W791*) truncated mutation of CSF3R. These findings elucidate a novel paradigm of CNL pathogenesis and explain how mutations drive the development of the disease. The order of acquisition of CSF3R mutations relative to mutations in epigenetic modifiers and the spliceosome have been determined only in isolated case reports; thus, further work is needed to understand the impact of mutation chronology on the clonal evolution and progression of CNL.

Public water supply facilities are vulnerable to intentional intrusion. In particular, Water Distribution Network (WDN) has become one of the most important public facilities that are prone to be attacked because of its wide coverage and constant open operation. In recent years, water contamination incidents happen frequently, causing serious losses and impacts to the society. Various measures have been taken to tackle this issue. Pollution or contamination isolation by localizing the contamination via sensors and scheduling certain valves have been regarded as one of the most promising solutions. The main challenge is how to schedule water valves to effectively isolate contamination and reduce the residual concentration of contaminants in WDN. In this paper, we are motivated to propose a reinforcement learning based method for valve real time scheduling by treating the sensing data from the sensors as state, and the valve scheduling as action, thus we can learn scheduling policy from uncertain contamination events without precise characterization of contamination source. Simulation results show that our proposed algorithm can effectively isolate the contamination and reduce the risk exclosure to the customers.

Background: The serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China., Methods: We recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR)., Results: We found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis., Conclusions: The present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.

Background: Uremic encephalopathy (UE), a toxic metabolic encephalopathy, is an uncommon complication resulting from endogenous uremic toxins in patients with severe renal failure. UE syndrome can range from mild inattention to coma. The imaging findings of UE include cortical or subcortical involvement, basal ganglia involvement and white matter involvement. The basal ganglia type is uncommon, although previous cases have reported that Asian patients with diabetes mellitus (DM) are usually affected., Case Presentation: A 32 year-old woman with a history of non-diabetic hemodialysis for 3 years suffered from severe involuntary movement, and brain magnetic resonance imaging showed symmetrical T2-weighted imaging (T2WI) and T2/fluid-attenuated inversion recovery (T2FLAIR) hyperintense nonhemorrhagic lesions in the bilateral basal ganglia. She was diagnosed with UE as syndrome of bilateral basal ganglia lesions, due to a combined effect of uremic toxins and hyperthyroidism. After treatment with high frequency and high flux dialysis, hyperbaric oxygen therapy and declining parathyroid hormone, the patient achieved complete remission with normal body movement and was discharged., Conclusion: UE with basal ganglia involvement is uncommon, although generally seen in Asian patients with DM. Our case reported a hemodialysis patient that had non-diabetic UE with typical bilateral basal ganglia lesions, presenting with involuntary movement.

Background: Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated., Methods: Human THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM-promoted tumor migration was detected using western blotting., Results: Here we found that AS-IV significantly inhibited IL-13 and IL-4-induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM-induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV., Conclusions: AS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV's ability to inhibit the metastasis of lung cancer.

Objective: To compare the osteogenic effects of a nano-sized 58S bioactive glass (nano-58S BG) and a traditional 45S5 bioactive glass(45S5 BG) in penetrating parietal critical bone defects., Methods: Critical bone defect with 9 mm diameter was created in the parietal bone of New Zealand rabbits. The bone defects were then filled with either nano-58S BG, or 45S5 BG, or nothing but the newly-formed blood clot as the blank control at random. For histological observation, specimens were gained 4 and 8 weeks after the surgery, sectioned and stained by HE. The amount of collagen type I was observed with Picric-Sirius Red staining through polarimetry. To observe the new bone formation with fluorescence under the laser confocal microscope, we injected fluorescent markers 14, 28, and 42 days after the surgery. The markers were tetracycline hydrochloride, alizarin red and calcin individually in chronological order. Image J software was used to quantify the bone regeneration., Results: HE staining showed that BG particulates were integrated with the surrounding tissue without any inflammatory cells infiltration 4 weeks after surgery. New bone regeneration was observed both from the border and in the center of the defects in both BG groups. No bone regeneration in defect center was observed in control group. At the end of 8 weeks, there was more bone regeneration in nano-58S group compared with 45S5 group and control group. The structure of the new bone in BG groups was hollow, which was similar to the natural normal parietal bone. No hollow structure was observed in the new bone of control group. Picric-sirius Red polarimetry showed that more amount of collagen type I was found in nano-58S group than in either 45S5 or control group. The fluorescent observation of the hard tissue slices at the end of 8 weeks showed statistically larger scope and faster new bone formation in nano-58S group with (29.4±4.48) μm thickness from 4-6 weeks and (35.3±3.74) μm from 6-8 weeks compared with 45S5 group [(13.43±3.44) μm and (17.64±4.13) μm] and control group [(5.88±2.92) μm and (6.07±3.02) μm, P<0.01]., Conclusion: Compared with the traditional 45S5 bioactive glass, 58S nano-sized bioactive glass showed better osteogenic effect in bone regeneration in parietal bones of rabbits.

Objective: Glucose transporter-1 (GLUT-1) as the major glucose transporter present in human cells is found overexpressed in a proportion of human malignancies. This meta-analysis is attempted to assess the prognostic significance of GLUT-1 for survival in various cancers., Materials and Methods: We conducted an electronic search using the databases PubMed, Embase and Web of Science, from inception to Oct 20th, 2016. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated., Results: Fourty-one studies with a total of 4794 patients were included. High GLUT-1 expression was significantly associated with poorer prognosis [overall survival: HR = 1.833 (95% CI: 1.597-2.069, P < 0.0001); disease-free survival: HR = 1.838 (95% CI: 1.264-2.673, P < 0.0001); progression-free survival: HR = 2.451 (95% CI: 1.668-3.233, P < 0.0001); disease specific survival: HR = 1.96 (95% CI: 1.05-2.871, P < 0.0001)]., Conclusions: High GLUT-1 expression may be an independent prognostic marker to predict poor survival in various types of cancers. Further clinical trials with high quality need to be conducted to confirm our conclusion., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing interests in relation to the work described.

Background: Patients with thoracic neuropathic pain often do not respond to medication and physical therapy. Coblation technology has been demonstrated to have potential for pain management., Methods: Fifteen patients underwent computed tomography-guided percutaneous coblation to ablate the thoracic paravertebral nerve for their medication-resistant thoracic neuropathic pain. The pain intensity was assessed by visual analog scale (VAS) 1 day before surgery and 1 week and 1, 3, and 6 months after surgery, and the difference between preoperative and postoperative VAS values was determined to evaluate the pain relief effectiveness. Patients who achieved > 50% pain relief were defined as responders, and the ratio in all patients was calculated. The number of patients who reported mild pain (VAS ≤ 3) was recorded, and the ratio in all responders was calculated. In addition, adverse effects were also recorded to investigate the security of procedure., Results: Twelve (80%) responders achieved > 50% pain relief. The VAS score of responders significantly decreased from 7.42 ± 1.38 before surgery to 2.17 ± 1.11 (P = 0.000), 1.92 ± 1.16 (P = 0.000), 1.75 ± 0.97 (P = 0.000), and 1.58 ± 1.08 (P = 0.000) at 1 week, 1, 3, and 6 months after surgery, respectively. The number of responders with mild pain was 10 (83.3%), 11 (91.7%), 12 (100%), and 12 (100%) at 1 week, 1, 3, and 6 months after surgery, respectively. All responders and 1 nonresponder reported slight numbness after the surgery., Conclusion: Percutaneous thoracic paravertebral nerve coblation guided by computed tomography is a potential method for the treatment of thoracic neuropathic pain., (© 2016 World Institute of Pain.)