Suppressing memory associations impacts decision-making preference: Evidence from the think/no-think paradigm.

Recent research has suggested that episodic memory can guide our decision-making. Forgetting is one essential characteristic of memory. If certain memories are suppressed to be forgotten, decisions that rely on such memories should be impacted. So far, little research has examined whether suppression of episodic memory would impact decision-making. In the current pre-registered study, the effect of memory suppression on subsequent reinforcement decision-making was examined by combining the Think/No-think paradigm and a reinforcement decision-making task. We found that suppressing memories of learned associations significantly impaired recollected memories of those associations, and participants' decision bias disappeared after their memory associations were suppressed. Furthermore, the more memory associations participants recalled, the higher decision preferences they exhibited. Our findings provide additional support for the role of episodic memory in reinforcement decision-making, and suggest that suppressing memory associations can lead to behavioral consequences.

Inducing emotionally negative nonbelieved memories using negative pictures.

Memories that can be recalled but are no longer believed are termed nonbelieved memories. The current studies examined the creation of emotionally negative nonbelieved memories after viewing negatively valenced pictures. In both experiments, participants took part in two sessions. In Session 1, after being presented with a set of neutral and negative pictures, participants had to rate their emotional state. One week later, in Session 2, participants had to complete a recognition task to identify pictures that had appeared during the previous session. During this task, participants' memories for some pictures were challenged by telling them that their answers were incorrect in order to evoke nonbelieved memories. The experimental procedure was successful in creating nonbelieved memories in the participants. Specifically, in Experiment 1 (N = 35), we induced nonbelieved true memories for both negative and neutral pictures. We found a significant decrease in both belief and recollection after the challenge, with the change in belief being twice as large as the change in recollection. In Experiment 2 (N = 43), we successfully induced both nonbelieved true and false memories for negative pictures. Again, the reduction of belief was significantly greater than that of recollection. In general, participants evinced better memory for negative pictures, but following challenges people were just as likely to accept false social feedback and change their memories regarding other types of pictures. In both experiments, our challenges did not lead to notable changes in emotional state. In general, our findings show that emotionally negative nonbelieved memories can be successfully evoked in an experimental setting.

The effects of forewarning and divided attention on context retrieval in false recognition.

After studying a list of words that are semantically associated to a critical lure, participants are more likely to attribute a falsely recognised critical lure to the context of its strong than weak semantic associates. This is known as the source-strength effect. The current study investigated the roles of automatic and controlled processing in context retrieval in false recognition that is demonstrated by the source-strength effect. The results revealed that the source-strength effect was impervious to forewarning (Experiment 1) and remained intact when attentional resources at encoding were reduced (Experiment 2), suggesting that context retrieval in false recognition is based on automatic processes that are not amenable to conscious control and do not require many attentional resources. This interpretation is consistent with the associative activation theory, which proposes that context retrieval in false recognition is based on memory associations between contexts and critical lures that are automatically created when critical lures become automatically activated via spreading activation process.

Identification and Functional Mechanism Verification of Novel MicroRNAs Associated with the Fibrosis Progression in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a serious threat to human health worldwide, and its incidence is increasing annually. A growing amount of information is emerging about the role of micoRNAs (miRNAs) in the regulation of renal fibrosis, which has aroused interest in the development of drugs that block pathogenic miRNAs or restore protective miRNAs levels. To clarify the role of miRNAs in CKD, we selected patients with significant renal fibrotic disease (diabetic nephropathy (DN) and focal segmental glomerulosclerosis (FSGS)) as the disease group, and patients with little or no renal fibrotic disease (minimal change disease (MCD) and renal carcinoma adjacent to normal kidney) as controls. Significantly differentially expressed miRNAs were obtained by human kidney tissue sequencing, subsequently verified in mice models of DN and FSGS, and subsequently inhibited or overexpressed in human renal tubular epithelial cells (HK-2) stimulated by high glucose (HG) and TGF-ß1 in vitro. Therefore, the mechanism of its action in renal fibrosis was further elaborated. Finally, the downstream target genes of the corresponding miRNAs were verified by bioinformatics analysis, qRT-PCR, western blot and double luciferase report analysis. Two novel miRNAs, hsa-miR-1470-3p (miR-1470) and hsa-miR-4483-3p (miR-4483), were detected by renal tissue sequencing in the disease group with significant renal fibrosis (DN and FSGS) and the control group with little or no renal fibrosis (MCD and normal renal tissue adjacent to renal carcinoma). Subsequent human renal tissue qRT-PCR verified that the expression of miR-1470 was significantly increased, while the expression of miR-4483 was markedly decreased in the disease group (p < 0.05). Moreover, in vivo DN and FSGS mice models, the expression levels of miR-1470 and miR-4483 were consistent with the results of human kidney tissue. In vitro, miR-4483 was suppressed, whereas miR-1470 was induced by treatment with TGF-ß1 or HG. Inhibition of miR-1470 or overexpression of miR-4483 promoted HG or TGF-ß1-induced fibrosis in HK-2 cells. Further study revealed that MMP-13 and TIMP1 were the target genes ofmiR-1470 and miR-4483, respectively. Our study identifies newly dysregulated miRNA profiles related to fibrosis kidneys. miR-1470 and miR-4483 are demonstrated to participate in kidney fibrosis by regulation of MMP-13, TIMP1 respectively. Our results may represent a promising research direction for renal disorders and help identify new biomarkers and therapeutic targets for CKD.

Self-relevance enhances susceptibility to false memory.

Eyewitness testimony serves as important evidence in the legal system. Eyewitnesses of a crime can be either the victims themselves-for whom the experience is highly self-referential-or can be bystanders who witness and thus encode the crime in relation to others. There is a gap in past research investigating whether processing information in relation to oneself versus others would later impact people's suggestibility to misleading information. In two experiments (Ns = 68 and 122) with Dutch and Chinese samples, we assessed whether self-reference of a crime event (i.e., victim vs. bystander) affected their susceptibility to false memory creation. Using a misinformation procedure, we photoshopped half of the participants' photographs into a crime slideshow so that they saw themselves as victims of a nonviolent crime, while others watched the slideshow as mock bystander witnesses. In both experiments, participants displayed a self-enhanced suggestibility effect: Participants who viewed themselves as victims created more false memories after receiving misinformation than those who witnessed the same crime as bystanders. These findings suggest that self-reference might constitute a hitherto new risk factor in the formation of false memories when evaluating eyewitness memory reports.

Assessing the effects of drought on rainfed maize water footprints based on remote sensing approaches.

BACKGROUND: Drought affects the characteristics of water use during crop production and so quantitatively evaluating the impacts is important. However, it remains unclear how crop water use responds to drought. To address this gap, water footprint (WF) and standardized precipitation evapotranspiration index (SPEI) were calculated by remote sensing approaches to assess the effects of drought on crop water use. Rainfed maize is the most important crop in Jilin Province, and its growth and water use are more susceptible to drought. The present study explored not only the impact of growing season drought on the maize WF values in Jilin Province, but also the response of WF values to drought at different time scales. RESULTS: Spatially, 72.94% of the WFblue pixels showed a non-significant increase, and the WFgreen in 68% pixels decreased significantly, being mainly concentrated in the middle region. Furthermore, the pixels affected by monthly time scale drought were mainly in the middle region, whereas the pixels affected by annual time scale drought were mainly in the western region. CONCLUSION: Drought not only affected on the source and structure of agricultural water consumption, but also had different effects on WF values at different time scale. These effects had obvious spatial differences. The present study systematically explored the effects of drought on the WF values for rainfed maize in different climate regions and a consideration of these effects could provide valuable information on rainfed maize growth and the agricultural water use response to a changing climate. © 2023 Society of Chemical Industry.

Challenging memories reduces intrusive memories and the memory amplification effect.

This study scrutinizes the influence of attenuating beliefs about the veracity of traumatic experiences on the manifestation of intrusive recollections and the memory amplification effect. Participants were exposed to distress-inducing visual stimuli, subsequently rating their emotional status pre and post exposure. They engaged in a recognition task, identifying scenarios within the stimuli. Participants' recall was contested, casting doubt about the occurrence of certain scenes. Subsequently, they maintained a daily log of intrusive memories over a week. A second session reiterated the same process. This method effectively diminished the certainty in the participants' traumatic memories. Scenes whose occurrence was contested demonstrated a significant decline in both intrusive memories and memory amplification when juxtaposed with uncontested ones. Interestingly, no significant correlation emerged between the diminished belief in traumatic incidents and reductions in intrusive memory or memory amplification. Thus, this study advocates that interrogating the veracity of traumatic recollections can mitigate the prevalence of intrusive memories and the memory amplification effect, suggesting a novel potential therapeutic approach for trauma-related disorders.

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.

Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 µg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).

The role of microRNA-155 in glomerular endothelial cell injury induced by high glucose.

OBJECTIVE: To investigate the role of microRNA-155-5p on apoptosis and inflammatory response in human renal glomerular endothelial cells (HRGEC) cultured with high glucose. METHODS: The primary HRGEC were mainly studied, light microscopy was used to detect changes in cell morphology. Quantitative Real Time-Polymerase Chain Reaction, Western Blot, immunofluorescence were aimed to observe the mRNA and protein expression levels of target gene ETS-1, downstream factors VCAM-1, MCP-1 and cleaved caspase-3 in each group after high glucose treatment as well as transfection with miR-155 mimics or inhibitor. RESULTS: The expression of inflammatory factors and apoptosis of HRGEC cells increased under high glucose treatment. Compared with normal-glucose treatment, the expression of microRNA-155 markedly increased in HRGECs treated with high-glucose, as well as the mRNA and protein levels of ETS-1, VCAM-1, MCP-1 and cleaved caspase-3. Overexpression of microRNA-155 remarkably downregulated mRNA and protein levels of ETS-1, VCAM-1, MCP-1 and cleaved caspase-3, whereas miRNA-155 knockdown upregulated their levels. In addition, HRGEC cells were transfected with miR-155 mimics and ETS-1 siRNA with high glucose stimulation. The expression of ETS-1 was positively correlated with the expression of downstream factors VCAM-1 and MCP-1. These results suggest that ETS-1 can mediate endothelial cell inflammation by regulating VCAM-1 and MCP-1. CONCLUSION: MiR-155 can negatively regulate the expression of target gene ETS-1 and its downstream factors VCAM-1, MCP-1 and cleaved caspase-3, thus mediating the inflammatory response and apoptosis of HRGEC.

Randomized Control Study on Hemoperfusion Combined with Hemodialysis versus Standard Hemodialysis: Effects on Middle-Molecular-Weight Toxins and Uremic Pruritus.

INTRODUCTION: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. METHODS: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (ß2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of ß2M and PTH, while the secondary outcome was the reduction of the pruritus score. RESULTS: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of ß2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. CONCLUSION: The long-term HP + HD can reduce ß2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

MicroRNA-329 upregulation impairs the HMGB2/ß-catenin pathway and regulates cell biological behaviors in melanoma.

Melanoma is responsible for the majority of deaths caused by skin cancer. Antitumor activity of microRNA-329 (miR-329) has been seen in several human cancers. In this study, we identify whether miR-329 serves as a candidate regulator in melanoma. Melanoma-related differentially expressed genes were screened with its potential molecular mechanism predicted. Melanoma tissues and pigmented nevus tissues were collected, where the levels of miR-329 and high-mobility group box 2 (HMGB2) were determined. To characterize the regulatory role of miR-329 on HMGB2 and the ß-catenin pathway in melanoma cell activities, miR-329 mimics, miR-329 inhibitors, and siRNA-HMGB2 were transfected into melanoma cells. Cell viability, migration, invasion, cell cycle, and apoptosis were assessed. miR-329 was predicted to influence melanoma by targeting HMGB2 via the ß-catenin pathway. High level of HMGB2 and low miR-329 expression were observed in melanoma tissues. HMGB2 was targeted and negatively regulated by miR-329. In melanoma cells transfected with miR-329 mimics or siRNA-HMGB2, cell proliferation, migration, and invasion were impeded, yet cell cycle arrest and apoptosis were promoted, corresponding to decreased levels of ß-catenin, cyclin D1, and vimentin and increased levels of GSK3ß and E-cadherin. Collectively, our results show that miR-329 can suppress the melanoma progression by downregulating HMGB2 via the ß-catenin pathway.

Manipulating memory associations changes decision-making preferences in a preconditioning task.

Memories of past experiences can guide our decisions. Thus, if memories are undermined or distorted, decision making should be affected. Nevertheless, little empirical research has been done to examine the role of memory in reinforcement decision-making. We hypothesized that if memories guide choices in a conditioning decision-making task, then manipulating these memories would result in a change of decision preferences to gain reward. We manipulated participants' memories by providing false feedback that their memory associations were wrong before they made decisions that could lead them to win money. Participants' memory ratings decreased significantly after receiving false feedback. More importantly, we found that false feedback led participants' decision bias to disappear after their memory associations were undermined. Our results suggest that reinforcement decision-making can be altered by false feedback on memories. The results are discussed using memory mechanisms such as spreading activation theories.

A self-reference false memory effect in the DRM paradigm: Evidence from Eastern and Western samples.

It is well established that processing information in relation to oneself (i.e., self-referencing) leads to better memory for that information than processing that same information in relation to others (i.e., other-referencing). However, it is unknown whether self-referencing also leads to more false memories than other-referencing does. In the current two experiments with European and East Asian samples, we presented participants the Deese-Roediger-McDermott lists together with their own name or other people's name (i.e., "Trump" in Experiment 1 and "Li Ming" in Experiment 2). We found consistent results across the two experiments; that is, in the self-reference condition, participants had higher true and false memory rates compared with those in the other-reference condition. Moreover, we found that self-referencing did not exhibit superior mnemonic advantage in terms of net accuracy compared with other-referencing and neutral conditions. These findings are discussed in terms of theoretical frameworks such as spreading activation theories and the fuzzy-trace theory. We propose that our results reflect the adaptive nature of memory in the sense that cognitive processes that increase mnemonic efficiency may also increase susceptibility to associative false memories.

Proteomic Analysis of Normal Expression Differences Exist in Bacillus Subtilis 168 Cultivation.

Biological science discovery often involves comparing conditions to a normal state, but little is known about "normal." Therefore, we used proteomic strategy to compare data from replicate samples of Bacillus subtilis 168 which were grown under identical condition. The results show that 294 differentially expressed proteins were annotated in 88 Gene Ontology functional groups and enriched in 13 KEGG pathways. We assume that normal expression differences are associated with adaptation to diverse environments. Moreover, five proteins (CotY, ThiG, SspA, SspB, and SspE) and their related genes were identified as having significantly different expressions at translational and transcriptional levels. Most of them are related to stress resistance and germination, indicating that normal expression differences can be regarded as a rapid response mechanism for survival. However, unstable protein expression may cause some fermentative problems that were observed in histidine and sulfur metabolism pathways. Our study facilitates dissection of the influence of biological variance on cultivation safety and stability.

Exploring the consequences of nonbelieved memories in the DRM paradigm.

In the current experiments, we attempted to elicit nonbelieved memories (NBMs) using the Deese/Roediger-McDermott (DRM) false memory paradigm. Furthermore, by using this approach, we explored the consequences of nonbelieved true and false memories. In Experiments 1 and 2, participants received several DRM wordlists and were presented with a recognition task. After the recognition task, participants' statements were contradicted by giving them feedback about true and false items. In this way, we succeeded in eliciting nonbelieved true and false memories. In Experiment 2, participants were also involved in a modified perceptual closure task after receiving belief-relevant feedback. In this task, participants received degraded visual representations of words (e.g., false and true) that became clearer over time. Participants had to identify them as fast as possible. We also measured dissociation, compliance, and social desirability. We found that undermining belief had contrasting consequences for true and false memories. That is, nonbelieved true memories were identified more slowly whereas nonbelieved false memories were identified more quickly. We did not find any relation between our individual differences measures and the formation of NBMs.

Undermining belief in false memories leads to less efficient problem-solving behaviour.

Memories of events for which the belief in the occurrence of those events is undermined, but recollection is retained, are called nonbelieved memories (NBMs). The present experiments examined the effects of NBMs on subsequent problem-solving behaviour. In Experiment 1, we challenged participants' beliefs in their memories and examined whether NBMs affected subsequent solution rates on insight-based problems. True and false memories were elicited using the Deese/Roediger-McDermott (DRM) paradigm. Then participants' belief in true and false memories was challenged by telling them the item had not been presented. We found that when the challenge led to undermining belief in false memories, fewer problems were solved than when belief was not challenged. In Experiment 2, a similar procedure was used except that some participants solved the problems one week rather than immediately after the feedback. Again, our results showed that undermining belief in false memories resulted in lower problem solution rates. These findings suggest that for false memories, belief is an important agent in whether memories serve as effective primes for immediate and delayed problem-solving.

[MiR-155 Inhibits the Expression of MMPs in HK2 Cells by Targeting KLF4].

OBJECTIVES: To determine whether miR -155 inhibits the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in HK2 cells by targeting Kruppel-like factor 4 (KLF4). METHODS: MiR -155-mimic, miR -155-NC empty plasmid, and culture medium were transfected into renal tubular epithelial cells, respectively. Six hours later, the expression of miR -155 was detected by real time-PCR; the expressions of MMP-2, MMP-9 and KLF4 were detected by Western blot; and the activity of MMP-2 and MMP-9 in the cells was detected by gelatin zymography. Because KLF4 was predicted as the target gene of miR -155 by bioinformatics. The miR-155 overexpressed HK2 cells were transfected with KLF4 overexpression plasmid or empty plasmid. Six hours later, the expressions of MMP-2, MMP-9 and KLF4, and the activity of MMP-2 and MMP-9 were measured again. Finally, cells containing luciferase plasmids with KLF4-3!d-UTR wild type (WT) or mutant (MUT) sequence were constructed and transfected with miR -155-mimic or empty plasmid. Luciferase assay was used to confirm whether KLF4 -3!d-UTR was the binding site in targeting miR -155#. RESULTS: Compared with the cells transfected with empty plasmid, the expression of miR -155 was up-regulated and the expressions of MMP-2, MMP-9 and KLF4 were down-regulated in the cells transfected with miR -155-mimic. Compared with the cells transfected with miR -155 mimic or miR -155 mimic+empty plasmid, the expressions of MMP-2, MMP-9 and KLF4 were up-regulated in the KLF4+miR -155 transfected cells. Luciferase assays confirmed that miR -155 binds to KLF4 , and KLF4 -3!d-UTR is the target gene of miR -155. CONCLUSION: MiR-155 inhibits the expressions of MMP-2 and MMP-9 in HK2 cells by targeting KLF4 -3!d-UTR.

Acute kidney injury in China: a cross-sectional survey.

BACKGROUND: Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of AKI and assess the availability of diagnosis and treatment in China. METHODS: We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and National Bureau of Statistics. FINDINGS: Of 2,223,230 patients admitted to the 44 hospitals screened in 2013, 154,950 (7·0%) were suspected of having AKI by electronic screening, of whom 26,086 patients (from 374,286 total admissions) were reviewed with medical records to confirm the diagnosis of AKI. The detection rate of AKI was 0·99% (3687 of 374,286) by KDIGO criteria and 2·03% (7604 of 374,286) by expanded criteria, from which we estimate that 1·4-2·9 million people with AKI were admitted to hospital in China in 2013. The non-recognition rate of AKI was 74·2% (5608 of 7555 with available data). Renal referral was done in 21·4% (1625 of 7604) of the AKI cases, and renal replacement therapy was done in 59·3% (531 of 896) of those who had the indications. Delayed AKI recognition was an independent risk factor for in-hospital mortality, and renal referral was an independent protective factor for AKI under-recognition and mortality INTERPRETATION: AKI has become a huge medical burden in China, with substantial underdiagnosis and undertreatment. Nephrologists should take the responsibility for leading the battle against AKI. FUNDING: National 985 Project of China, National Natural Science Foundation of China, Beijing Training Program for Talents, International Society of Nephrology Research Committee, and Bethune Fund Management Committee.

Foci of Entotic Nuclei in Different Grades of Noninherited Renal Cell Cancers.

We report here an intriguing pattern in nuclear appearance of renal clear cell cancer. In low grade clear cell cancer, detailed examination showed that in many cells, two or more nuclei were within the confines of a single cell membrane. This likely resulted from a cell being contained within its neighboring cell. Consequently, this resulted in appearance of multicellularity. This appearance of the nuclei were not associated with mitotic figures, suggesting that these did not result from nuclear fission. Additionally, the cells containing this nuclei did not show any evidence of cytokinesis including equatorial tapering, suggesting that the process may have resulted from cytokinesis failure. In some sections of higher grade clear cell cancer, these appearance were higher, though we did not observe any frank syncytium formation. On careful observation, there were isolated events of fusion of nuclei within a single cell in different grades of renal cell cancers. There occurrence was more frequent in higher grades of clear cell renal cancer and metastatic clear cell carcinoma. These features were also demonstrable in multiple fields of lower grades of clear cell carcinoma. This phenomenon of entosis may contribute to aneuploidy and tumor progression to dysplastic stages and genomic instability in renal cancers. Future studies are aimed at delineating the cell-cell boundaries and the mechanism contributing to this observation, either from peripheral cell engulfing or failure of cytosolic division for cell separation.