Serum uric acid levels and health outcomes in CKD: a prospective cohort study.

BACKGROUND: Hyperuricemia is prevalent in individuals with chronic kidney disease (CKD). Elevated serum uric acid (SUA) concentrations have been considered an independent risk factor for the onset of CKD. However, the relationship between SUA concentrations and long-term health outcomes among patients with CKD remains unclear. METHODS: We performed a prospective cohort study with nationally representative sample to investigate the relationship between SUA concentrations and mortality risk including all-cause, cardiovascular disease (CVD) and cancer mortality, among patients with CKD. The weighted restricted cubic spline analyses combined with the multivariate-adjusted Cox proportional hazard models were used to test the nonlinearity of relationship. RESULTS: The 6642 patients participating in National Health and Nutrition Examination Survey 1999-2018 were enrolled. During 656 885 person-months of follow-up time, 2619 all-cause deaths were recorded, including 1030 CVD deaths and 458 cancer deaths. Our study presented J-shaped non-linear relationships between SUA concentrations and all-cause and CVD mortality with inflection points at 311.65 µmol/L and 392.34 µmol/L, respectively. When SUA concentration was higher than those inflection points, every increase of 50 µmol/L SUA was associated with 11.7% and 17.0% greater multivariable-adjusted hazard ratio of all-cause and CVD mortality, respectively. In addition, a negative linear correlation with cancer mortality was detected. CONCLUSION: These findings suggested that maintaining appropriate SUA concentrations may improve long-term health outcomes among CKD patients. The corresponding inflection points of J-shaped non-linear relationships were 311.65 and 392.34 µmol/L for all-cause and CVD mortality. Further clinical trials are required to investigate uric acid-lowering targets.

Tolerability, safety and efficacy of a novel phosphate binder VS-505 (AP301): a Phase 2 dose-escalation and dose-ranging study in patients undergoing maintenance hemodialysis.

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1-2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2) and -1.4 (-2.2, -0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. CLINICAL TRIAL REGISTRATION NUMBER: NCT04551300 .

Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment.

Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays a crucial role in remodeling the tumor microenvironment (TME). Here, through the integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups of CAFs and described their spatial distribution characteristics. Additionally, the analysis of single-cell RNA sequencing (scRNA-seq) data from three additional common cancer types and two newly generated scRNA-seq datasets of rare cancer types, namely epithelial-myoepithelial carcinoma (EMC) and mucoepidermoid carcinoma (MEC), expanded our understanding of CAF heterogeneity. Cell-cell interaction analysis conducted within the spatial context highlighted the pivotal roles of matrix CAFs (mCAFs) in tumor angiogenesis and inflammatory CAFs (iCAFs) in shaping the immunosuppressive microenvironment. In patients with breast cancer (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity in facilitating cancer cell proliferation, promoting epithelial-mesenchymal transition (EMT), and contributing to the establishment of an immunosuppressive microenvironment. Furthermore, a scoring system based on iCAFs showed a significant correlation with immune therapy response in melanoma patients. Lastly, we provided a web interface ( https://chenxisd.shinyapps.io/pancaf/ ) for the research community to investigate CAFs in the context of pan-cancer.

LC-MS/MS method for determination of r-RGD-hirudin in human plasma and its application in pharmacokinetic study.

OBJECTIVE: This study aimed to develop a simple, sensitive, and selective Liquid chromatography with a Mass spectroscopic method for simultaneous quantification of a recombinant bifunctional hirudin (r-RGD-Hirudin, Bifunctional Hirudin, BFH) in human plasma and verify its effectiveness. METHODS: The analytes and the internal standards from human plasma were extracted using the solid-phase extraction technique. The reconstituted samples were chromatographed on Waters C18 column (BEH 50 × 2.1 mm, 1.7 µm) using a mixture of 0.1% formic acid/acetonitrile (85%/15%, v/v) with gradient elution as the initial mobile phase at a flow rate of 0.3 mL/min. RESULTS: The effectiveness of the proposed method was verified over the concentration range of 10-2000 ng/mL for r-RGD-Hirudin. A linear calibration curve was obtained. The precision and accuracy of BFH in the intra- and inter-day runs fell within the range of ±15% at LQC, GMQC, MQC and HQC concentrations. The extraction recoveries and matrix effect at two quality control (QC) levels for BFH were confirmed to conform to the relevant requirement. CONCLUSION: The proposed method was successfully adapted to examine the pharmacokinetics of BFH in 40 Chinese healthy volunteers, respectively.

Neuroprotection of exercise: P2X4R and P2X7R regulate BDNF actions.

The neurotrophin brain-derived neurotrophic factor (BDNF), which acts as a transducer, is responsible for improving cerebral stroke, neuropathic pain, and depression. Exercise can alter extracellular nucleotide levels and purinergic receptors in central nervous system (CNS) structures. This inevitably activates or inhibits the expression of BDNF via purinergic receptors, particularly the P2X receptor (P2XR), to alleviate pathological progression. In addition, the significant involvement of sensitive P2X4R in mediating increased BDNF and p38-MAPK for intracerebral hemorrhage and pain hypersensitivity has been reported. Moreover, archetypal P2X7R blockade induces mouse antidepressant-like behavior and analgesia by BDNF release. This review summarizes BDNF-mediated neural effects via purinergic receptors, speculates that P2X4R and P2X7R could be priming molecules in exercise-mediated changes in BDNF, and provides strategies for the protective mechanism of exercise in neurogenic disease.

Randomized controlled trial of nalfurafine for refractory pruritus in hemodialysis patients.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods: In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 µg, 2.5 µg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results: A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 µg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 µg and placebo group was 8.81 mm, but not statistically significantly different. Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5µg, 38.6% in 2.5 µg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions: Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

Extracorporeal Treatment for Gabapentin and Pregabalin Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup.

Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as "dialyzable" for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence).

Glucose-induced decrease of cystathionine ß-synthase mediates renal injuries.

Exogenous hydrogen sulfide (H2 S) protects kidneys from diabetic injuries in animal models. In order to explore the role of endogenous H2 S in diabetic nephropathy, we determined the renal H2S producing enzymes in vivo and in vitro. In diabetic mice, H2 S levels in blood and kidney were decreased while cystathionine ß-synthase (CBS), mainly located in mouse renal proximal convoluted tubules (PCT), was reduced selectively. In cultured mouse PCT cells treated with high glucose, CBS protein and activity was reduced while ubiquitinated CBS was increased, which was abolished by a proteasome inhibitor MG132 at 1 hour; high glucose drove CBS colocalized with proteasome 26S subunit ATPase6, indicating an involvement of ubiquitination proteasome degradation. At 48 hours, high glucose also selectively decreased CBS protein, concentration-dependently, but increased the ubiquitination of CBS; silence of CBS by siRNA increased nitrotyrosine, a marker for protein oxidative injury. Nitrotyrosine was also increased by high glucose treatments. The increases of nitrotyrosine either by cbs-siRNA or by glucose were restored by GYY4137, indicating that the H2 S donor may protect kidney from oxidative injury induced by CBS deficiency. In diabetic kidneys, ubiquitinated CBS and nitrotyrosine were increased but restored by GYY4137. The treatment also ameliorated albuminuria and renal morphologic changes in diabetic mice. Our findings suggest that high glucose induces reduction of renal CBS protein and activity in vivo and in vitro that is critical to the pathogenesis of diabetic kidney disease.

Uremic toxin indoxyl sulfate induces dysfunction of vascular smooth muscle cells via integrin-ß1/ERK signaling pathway.

BACKGROUND: Protein-bound uremic toxins (PBUTs) are reported to be one of the major culprits in chronic kidney disease-cardiovascular disease (CKD-CVD) development, yet its mechanism is not fully clear. Our previous study confirmed elevated expression of integrin-ß1 (ITGß1) in vascular smooth muscle cells of uremic patients. Thus, this study aimed to explore the relationship between PBUTs and ITGß1 in uremic vasculature injury. METHODS: Human umbilical vein smooth muscle cells (HUVSMCs) and endothelial cells (HUVECs) were treated with two representative PUBTs, indoxyl sulfate (IS) and p-cresyl sulfate (PC). Both cells were measured for the expression of ITGß1 and downstream signaling pathways and assayed for proliferation, migration, adhesion and apoptosis. RESULTS: The IS treatments were observed with significantly up-regulated ITGß1 in HUVSMCs but not in HUVECs, while PC did not induce ITGß1 alteration in either HUVSMCs or HUVECs. Furthermore, overexpression of ITGß1 revealed activated downstream signal-regulated kinase (ERK) signaling pathway with promoted focal adhesion, migration, proliferation but no apoptosis in HUVSMCs by IS. These functional and pathway alterations could be significantly suppressed by RNA interference of ITGß1. More importantly, the application of ERK1/2 inhibitor significantly suppressed the focal adhesion, migration and proliferation of HUVSMCs. CONCLUSION: We first demonstrated that ITGß1/ERK signaling pathway mediated abnormal focal adhesion, migration and proliferation of vascular smooth muscle cells stimulated by IS. ITGß1/ERK signaling may serve as a novel therapeutic target for CKD-CVD.

Incidences and reasons of postoperative surgical site infection after lumbar spinal surgery: a large population study.

PURPOSE: The purpose of this study was to determine the incidences of postoperative acute surgical site infection (SSI) after lumbar spinal surgery and its possible reasons in our hospital during the past 9 years. METHODS: This is a retrospective study with a large sample size. The medical records of all included patients were reviewed, and patients with acute SSI were identified. The incidence and possible reasons of SSI were determined. RESULTS: A total of 7240 patients who underwent posterior lumbar spinal surgery were included in this study, and the total incidence of postoperative SSI was 1.53% (111/7240). Gram-negative bacteria were found to be dominant in postoperative wound infections after lumbar spinal surgery. And Escherichia coli were the most common pathogen in patients with SSI. The rate of postoperative SSI following lumbar spinal surgery was increased at first and then decreased during the past 9 years. Additionally, from 2011 to 2014, it was mainly deep infection in these patients, and then was mainly superficial infection from 2015 to 2019. Patients with lumbar spinal stenosis had the highest incidence of postoperative SSI (2.39%, P < 0.001). There was also a significant difference for the number of SSI cases among different surgeons. CONCLUSION: Based on a large population analysis, Gram-negative bacteria were the most common pathogen in postoperative SSI after lumbar spinal surgery. And patients with lumbar spinal stenosis had the highest incidence of SSI. Increasing the intervention of Gram-negative may be an important step to reduce the postoperative SSI after lumbar spinal surgery.

Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK.

A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and molecular levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1, and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. Also, 14(15)-EET (a major substrate of sEH), but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1, and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may positively regulate Ampk transcriptionally in mRMCs. This study provides insights into and therapeutic target for the HFD-mediated renal injury.

Water-Soluble, Alanine-Modified Fullerene C60 Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells.

As carbon-based nanomaterials, water-soluble C60 derivatives have potential applications in various fields of biomedicine. In this study, a water-soluble fullerene C60 derivative bearing alanine residues (Ala-C60) was synthesized. The effects of Ala-C60 on neural stem cells (NSCs) as seed cells were explored. Ala-C60 can promote the proliferation of NSCs, induce NSCs to differentiate into neurons, and inhibit the migration of NSCs. Most importantly, the Ala-C60 can significantly increase the cell viability of NSCs treated with hydrogen peroxide (H2O2). The glutathioneperoxidase (GSH-Px) and superoxide dismutase (SOD) activities and glutathione (GSH) content increased significantly in NSCs treated even by 20 µM Ala-C60. These findings strongly indicate that Ala-C60 has high potential to be applied as a scaffold with NSCs for regeneration in nerve tissue engineering for diseases related to the nervous system.

The Effect of RADA16-I and CDNF on Neurogenesis and Neuroprotection in Brain Ischemia-Reperfusion Injury.

Scaffold materials, neurotrophic factors, and seed cells are three elements of neural tissue engineering. As well-known self-assembling peptide-based hydrogels, RADA16-I and modified peptides are attractive matrices for neural tissue engineering. In addition to its neuroprotective effects, cerebral dopamine neurotrophic factor (CDNF) has been reported to promote the proliferation, migration, and differentiation of neural stem cells (NSCs). However, the role of RADA16-I combined with CDNF on NSCs remains unknown. First, the effect of RADA16-I hydrogel and CDNF on the proliferation and differentiation of cultured NSCs was investigated. Next, RADA16-I hydrogel and CDNF were microinjected into the lateral ventricle (LV) of middle cerebral artery occlusion (MCAO) rats to activate endogenous NSCs. CDNF promoted the proliferation of NSCs, while RADA16-I induced the neural differentiation of NSCs in vitro. Importantly, both RADA16-I and CDNF promoted the proliferation, migration, and differentiation of endogenous NSCs by activating the ERK1/2 and STAT3 pathways, and CDNF exerted an obvious neuroprotective effect on brain ischemia-reperfusion injury. These findings provide new information regarding the application of the scaffold material RADA16-I hydrogel and the neurotrophic factor CDNF in neural tissue engineering and suggest that RADA16-I hydrogel and CDNF microinjection may represent a novel therapeutic strategy for the treatment of stroke.

Inhibition of Quorum-Sensing Regulator from Pseudomonas aeruginosa Using a Flavone Derivative.

Quorum sensing (QS) is a cell-to-cell communication process that controls bacterial collective behaviors. The QS network regulates and coordinates bacterial virulence factor expression, antibiotic resistance and biofilm formation. Therefore, inhibition of the QS system is an effective strategy to suppress the bacterial virulence. Herein, we identify a phosphate ester derivative of chrysin as a potent QS inhibitor of the human pathogen Pseudomonas aeruginosa (P. aeruginosa) using a designed luciferase reporter assay. In vitro biochemical analysis shows that the chrysin derivative binds to the bacterial QS regulator LasR and abrogates its DNA-binding capability. In particular, the derivative exhibits higher anti-virulence activity compared to the parent molecule. All the results reveal the potential application of flavone derivative as an anti-virulence compound to combat the infectious diseases caused by P. aeruginosa.

Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricaemia: a randomized controlled phase II study.

OBJECTIVE: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. METHODS: This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. RESULTS: 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P < 0.05 for 5 mg and 10 mg SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg SHR4640 and benzbromarone, respectively, vs placebo (5.9%; P < 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. CONCLUSIONS: The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.

Quantitative proteomics by iTRAQ-PRM based reveals the new characterization for gout.

BACKGROUND: Gout is a common and complex form of immunoreactive arthritis based on hyperuricemia, while the symptoms would turn to remission or even got worse. So, it is hard to early identify whether an asymptomatic hyperuricemia (AHU) patient will be susceptible to get acute gout attack and it is also hard to predict the process of gout remission to flare. Here, we report that the plasma proteins profile can distinguish among acute gout (AG), remission of gout (RG), AHU patients, and healthy controls. METHODS: We established an isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM) based method to measure the plasma proteins for AG group (n = 8), RG group (n = 7), AHU group (n = 7) and healthy controls (n = 8). RESULTS: Eleven differentially expressed proteins such as Histone H2A, Histone H2B, Thrombospondin-1 (THBS1), Myeloperoxidase (MPO), Complement C2, Complement component C8 beta chain (C8B), Alpha-1-acid glycoprotein 1 (ORM1), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Carbonic anhydrase 1 (CA1), Serum albumin (ALB) and Multimerin-1 (MMRN1) were identified. Histone H2A, Histone H2B and THBS1 might be the strongest influential regulator to maintain the balance and stability of the gout process. The complement and coagulation cascades is one of the main functional pathways in the mechanism of gout process. CONCLUSIONS: Histone H2A, Histone H2B and THBS1 are potential candidate genes for novel biomarkers in discriminating gout attack from AHU or RG, providing new theoretical insights for the prognosis, treatment, and management of gout process. TRIAL REGISTRATION: This study is not a clinical trial.

Online education at the medical School of Tongji University during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: The global reputation of coronavirus disease (COVID-19) has led universities in China to conduct online teaching. However, the actual feedback from medical teachers and students regarding online education remains unclear. METHODS: A prospective questionnaire survey examined the current opinions of online education from teachers and students at the Medical School of Tongji University. RESULTS: A total of 488 valid questionnaires were collected (223 males, 45.7%; 265 females, 54.3%), including 394 students (80.7%) and 94 teachers (19.3%). Most teachers and students were "in favor of online teaching," had "positive views for online education," were "satisfied with online teaching," and "expected for regular online education," although students thought that "too much learning tasks had been assigned" (90.4% teachers vs. 43.1% students, P < 0.001) and "less teaching effect than in offline classes" (68.1% teachers vs. 43.4% students). Compared to female counterpart, male students had higher "learning interest" (27.6% vs. 14.9%), "learning attention" (29.2% vs. 14.4%), "learning efficiency" (30.2% vs. 16.7%), and "better learning effect" (27.6% vs. 15.3%). Furthermore, male students had a significantly rise in attendance rate. Compared with male teachers, female teachers had less "experience in online educational course recording" (25.9% vs. 50%) and "past training for online teaching" (53.7% vs. 77.5%). Furthermore, they tended to be more "resistant to online teaching" (44.4% vs. 22.5%) and less "ready for online teaching" (70.4% vs. 87.5%). There was no significant difference in the acceptance of online teaching among teachers in different age groups. CONCLUSIONS: Most teachers and students supported and were satisfied with the implementation of online education during the pandemic. Although teachers were less adaptable to online education, they still had positive opinions. Sex influenced the acceptance of online teaching. Male teachers and students showed better adaptability than their female counterparts. Although online teaching has advantages, it still cannot completely replace traditional offline teaching. As online education is a trend for future learning, universities should make more efforts to improve it, especially to provide more attention to female teachers and students.

Atypical teratoid/rhabdoid tumor in adult: case series and an integrated survival analysis.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is well documented in children but less so in adults because of its rarity. METHOD: We report a series of five cases, a literature review and quantitative analysis of the survival outcome of adult AT/RT patients. RESULTS: Seventy-four patients including our five cases (male: female = 16: 58) were evaluated, whose median age was 32.5 years (18-80 years). The commonest location was the sellar region. Median overall survival (OS) was 12.5 months (0.5-204.00 months). Chemotherapy was associated with OS (HR: 0.349, 95%CI: 0.176-0.694, p = 0.003), while other factors did not influence OS. From Kaplan-Meier analysis, surgery combining postoperative chemotherapy and radiotherapy was associated with better prognosis (Log Rank: χ2 = 14.662, p = 0.001). CONCLUSIONS: Adult AT/RT is commoner in females and tends to recur rapidly after surgical resection. Chemotherapy may provide a survival benefit. Surgery combined with postoperative chemotherapy and radiotherapy was associated with better prognosis for adult AT/RT patients, though the overall prognosis was still poor.

Efficient Synthesis of Phosphonamidates through One-Pot Sequential Reactions of Phosphonites with Iodine and Amines.

A one-pot sequential strategy to construct phosphonamidates has been developed by generating phosphonites in situ from arylmagnesium bromides and triethyl phosphite followed by treatment with iodine and amines. A variety of phosphonamidates were obtained with good to excellent yields at room temperature from easily available materials.

Lithium targeting of AMPK protects against cisplatin-induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells.

Autophagy has been demonstrated to be vital for kidney homeostasis and is centrally implicated in the pathogenesis of cisplatin-induced acute kidney injury (AKI). Lithium is a potent autophagy inducer in a number of cell types. However, it remains uncertain whether its autophagic activity is associated with a beneficial effect on renal tubular cells in AKI. This study aimed to examine the effect of lithium on renal autophagy in cisplatin-induced AKI. Mice or renal proximal tubular epithelial cells in culture were exposed to cisplatin-induced acute injury in the presence or absence of lithium treatment. AKI or tubular cell injury was evaluated, and cell signaling associated with autophagy was examined. Lithium pretreatment prominently ameliorated acute renal tubular damage in mice exposed to cisplatin insult, associated with enhanced autophagy in renal tubules, as assessed by measuring microtubule-associated protein 1A/1B-light chain 3 (LC3)BII/I expression and autophagosome formation. Consistently, in cisplatin-injured renal tubular cells in vitro, lithium enhanced autophagic activities, improved cell viability, and attenuated cell death. Mechanistically, lithium triggered AMPK-α phosphorylation and activation, which in turn positively correlated with the induced expression of autophagy-related molecules, like mammalian target of rapamycin and LC3BII/I. AMPK-α activation is likely required for lithium-induced tubular cell autophagy and protection in cisplatin-induced AKI because blockade of AMPK-α phosphorylation by compound C markedly abrogated lithium-induced autophagosome formation and mitigated the protective effect of lithium on AKI. Our findings suggest that lithium represents a promising therapeutic strategy for protecting renal tubular cells against cisplatin-induced AKI by enhancing autophagy via AMPK-α activation.-Bao, H., Zhang, Q., Liu, X., Song, Y., Li, X., Wang, Z., Li, C., Peng, A., Gong, R. Lithium targeting of AMPK protects against cisplatin-induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells.