Erratum: Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury: Erratum.

[This corrects the article DOI: 10.7150/thno.54550.].

Orientation transitions and chiral assemblies of para-terphenyl molecules on Cd(0001).

The interplay between orientation transition and chiral self-assemblies of para-terphenyl (P3P) molecules on the Cd(0001) surface has been investigated using low temperature scanning tunneling microscopy and density functional theory calculations. Three distinct molecular orientations have been discerned from the self-assembled thin films of P3P. At the low coverage, flat-lying molecules appear in the homochiral domains with the incommensurate registry to the substrate. With the coverage increasing, the incoming molecules are incorporated into the first layer with edge-on orientation and form the self-assembled zigzag chains. The alternative arrangement of zigzag chains with opposite chirality leads to the formation of a c(4 × 2) superstructure, in which the tilted molecules exhibit orientational frustration and fuzzy noises. The analysis of the tunneling spectra reveals that the electronic structure of P3P layers is contingent upon the hybridization between the electronic states of P3P molecules and the Cd(0001) surface. These results provide important insights into the interplay between orientational transition and chiral assembly of P3P molecules on metal substrates.

Roxadustat on Renal Anemia with Macroinflammation: A Retrospective Cohort Study.

Introduction: Roxadustat, the first-in-class drug for the treatment of renal anemia, has demonstrated efficacy in renal anemia with microinflammation. Additional data are needed regarding the efficacy of roxadustat on renal anemia with systemic macroinflammation. Methods: Three cohorts of renal anemia based on the basic level of high-sensitivity CRP were included. Patients with hsCRP ≤2 mg/L were selected as non-inflammation (NI) group; 2< hsCRP ≤10 mg/L as microinflammation (MI) group; hsCRP≥10 mg/L as macroinflammation (MA) group. Patients received oral roxadustat three times per week for 52 weeks. The primary end point was the hemoglobin level over weeks 12-52. The second end point was the cumulative proportion of patients achieving hemoglobin response by the end of week 12. Results: A total of 107 patients with chronic kidney diseases (CKDs) were enrolled. Overall, the baseline hemoglobin level of patients was 79.99 ± 11.20 g/L. Roxadustat could significantly increase the hemoglobin level in all of the three groups and did not show any significant difference (p > 0.05, respectively). Meanwhile, compared with that of the NI group, there was no significant difference in hemoglobin response rate in the MA group both at week 12 (p = 0.06; 95% confidence interval [CI], 0.9531-13.75) and week 52 (p = 0.37; 95% CI, 0.5080-7.937). Moreover, the hemoglobin response was independent of baseline hsCRP level (p = 0.72, 95% CI, -0.1139 to 0.0794). More importantly, roxadustat significantly reduced ferritin and serum iron levels and increased total iron-binding capacity in the three groups, which showed no significant differences among the three groups (p > 0.05, respectively). Conclusion: Roxadustat significantly improves anemia in CKD patients with systemic macroinflammation.

The role of minimal residual disease and serum free light chain ratio in the management of multiple myeloma.

Multiple myeloma (MM) denotes a cancerous growth characterized by abnormal proliferation of plasma cells. Growing evidence suggests that the complexity in addressing MM lies in the presence of minimal residual disease (MRD) within the body. MRD assessment is becoming increasingly important for risk assessment in patients with MM. Similarly, the levels of serum free protein light chain and their ratio play a crucial role in assessing the disease burden and changes in MM. In this paper, we review and explore the utilization of MRD and serum free light chain ratio in the treatment of MM, delving into their respective characteristics, advantages, disadvantages, and their interrelation.

CD8 T cells induce the peritubular capillary rarefaction during AKI to CKD transition.

Acute kidney injury (AKI) transformed to chronic kidney disease (CKD) is a critical clinical issue characterized by tubulointerstitial inflammation (TII) and fibrosis. However, the exact mechanism remains largely unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to obtain a high-resolution profile of T cells in AKI to CKD transition with a mice model of unilateral ischemia-reperfusion injury (uIRI). We found that T cells accumulated increasingly with the progression of AKI to CKD, which was categorized into 9 clusters. A notably increased proportion of CD8 T cells via self-proliferation occurred in the early stage of AKI was identified. Further study revealed that the CD8 T cells were recruited through CXCL16-CXCR6 pathway mediated by macrophages. Notably, CD8 T cells induced endothelial cell apoptosis via Fas ligand-Fas signaling. Consistently, increased CD8 T cell infiltration accompanied with peritubular capillaries (PTCs) rarefaction was observed in uIRI mice. More impressively, the loss of PTCs and renal fibrosis was remarkably ameliorated after the elimination of CD8 T cells. In summary, our study provides a novel insight into the role of CD8 T cells in the transition from AKI to CKD via induction of PTCs rarefaction, which could suggest a promising therapeutic target for AKI.

HIF-1α and adaptor protein LIM and senescent cell antigen-like domains protein 1 axis promotes tubulointerstitial fibrosis by interacting with vimentin in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Activation of the renin-angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen-like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)-induced hypertension and tubulointerstitial fibrosis was investigated. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) renal tubular-specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II-induced renal interstitial fibrosis. In vitro, HIF-1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. KEY RESULTS: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II-induced hypertension model. Tubular-specific knockdown of LIMS1 ameliorated Ang II-induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF-1α in tubular cells and that tubular HIF-1α knockout ameliorates LIMS1-mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II-induced tubulointerstitial fibrosis by interacting with vimentin. CONCLUSION AND IMPLICATIONS: We conclude that HIF-1α transcriptionally regulated LIMS1 plays a central role in Ang II-induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II-induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.

Renal cell carcinoma in an adult-onset ESRD patient with nephronophthisis harboring NPHP3 deletion: A case report.

Background: Nephronophthisis (NPHP) is a rare autosomal recessive inherited tubulointerstitial nephropathy, the most prevalent genetic cause of end-stage renal disease (ESRD) in children. Convincing evidence indicated that the overall prevalence of NPHP in adult-onset ESRD is very likely to be an underestimation. Therefore, understanding the genetic background and clinicopathologic features of adult-onset NPHP is warranted. Case presentation: we reported one intriguing case with concurrent NPHP3 c.2694-2_2694-1delAG (splicing) variant and c.1082C > G (p.S361C) variant. A 48-year-old male was admitted to our hospital, complained about renal dysfunction for 10 years, and found right renal space-occupying lesion for 1 week. One of the most interesting clinical features is adult-onset ESRD, which differs from previous cases. Another discovery of this study is that the NPHP harboring NPHP3 deletion may be associated with clear cell renal cell carcinoma. Conclusion: In conclusion, we report two mutations in the NPHP3 gene that cause NPHP with adult-onset ESRD and renal clear cell carcinoma in a Chinese family, enriching the clinical features of NPHP.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Optimal intraventricular hemorrhage volume cutoff for predicting poor outcome in patients with intracerebral hemorrhage.

BACKGROUND AND OBJECTIVES: The prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. METHODS: We analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. RESULTS: The receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. CONCLUSIONS: Optimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.

CDK12 is a potential biomarker for diagnosis, prognosis and immunomodulation in pan-cancer.

Cell cycle-dependent protein kinase 12 (CDK12) plays a key role in a variety of carcinogenesis processes and represents a promising therapeutic target for cancer treatment. However, to date, there have been no systematic studies addressing its diagnostic, prognostic and immunological value across cancers. Here, we found that CDK12 was significantly upregulated in various types of cancers, and it expression increased with progression in ten cancer types, including breast cancer, cholangiocarcinoma and colon adenocarcinoma. Moreover, the ROC curves indicated that CDK12 showed diagnostic value in eight cancer types. High CDK12 expression was associated with poor prognosis in eight types of cancer, including low-grade glioma, mesothelioma, melanoma and pancreatic cancer. Furthermore, we conducted immunoassays to explore the exact mechanisms underlying CDK12-induced carcinogenesis, which revealed that increased expression of CDK12 allowed tumours to evade immune surveillance and upregulate immune checkpoint genes. Additionally, mutational studies have shown that amplification and missense mutations are the predominant mutational events affecting CDK12 across cancers. These findings establish CDK12 as a significant biological indicator of cancer diagnosis, prognosis, and immunotherapeutic targeting. Early surveillance and employment of CDK12 inhibitors, along with concomitant immunotherapy interventions, may enhance the clinical outcomes of cancer patients.

Locating Target Regions for Image Retrieval in an Unsupervised Manner.

Image retrieval performance can be improved by training a convolutional neural network (CNN) model with annotated data to facilitate accurate localization of target regions. However, obtaining sufficiently annotated data is expensive and impractical in real settings. It is challenging to achieve accurate localization of target regions in an unsupervised manner. To address this problem, we propose a new unsupervised image retrieval method named unsupervised target region localization (UTRL) descriptors. It can precisely locate target regions without supervisory information or learning. Our method contains three highlights: 1) we propose a novel zero-label transfer learning method to address the problem of co-localization in target regions. This enhances the potential localization ability of pretrained CNN models through a zero-label data-driven approach; 2) we propose a multiscale attention accumulation method to accurately extract distinguishable target features. It distinguishes the importance of features by using local Gaussian weights; and 3) we propose a simple yet effective method to reduce vector dimensionality, named twice-PCA-whitening (TPW), which reduces the performance degradation caused by feature compression. Notably, TPW is a robust and general method that can be widely applied to image retrieval tasks to improve retrieval performance. This work also facilitates the development of image retrieval based on short vector features. Extensive experiments on six popular benchmark datasets demonstrate that our method achieves about 7% greater mean average precision (mAP) compared to existing state-of-the-art unsupervised methods.

Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.

Sacubitril/valsartan ameliorates tubulointerstitial fibrosis by restoring mitochondrial homeostasis in diabetic kidney disease.

BACKGROUND: Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear. METHODS: Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro. RESULTS: We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor. CONCLUSIONS: Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.

Mitochondrial fumarate promotes ischemia/reperfusion-induced tubular injury.

AIM: Mitochondrial dysfunction, a characteristic pathological feature of renal Ischemic/reperfusion injury (I/RI), predisposes tubular epithelial cells to maintain an inflammatory microenvironment, however, the exact mechanisms through which mitochondrial dysfunction modulates the induction of tubular injury remains incompletely understood. METHODS: ESI-QTRAP-MS/MS approach was used to characterize the targeted metabolic profiling of kidney with I/RI. Tubule injury, mitochondrial dysfunction, and fumarate level were evaluated using qPCR, transmission electron microscopy, ELISA, and immunohistochemistry. RESULTS: We demonstrated that tubule injury occurred at the phase of reperfusion in murine model of I/RI. Meanwhile, enhanced glycolysis and mitochondrial dysfunction were found to be associated with tubule injury. Further, we found that tubular fumarate, which resulted from fumarate hydratase deficiency and released from dysfunctional mitochondria, promoted tubular injury. Mechanistically, fumarate induced tubular injury by causing disturbance of glutathione (GSH) hemostasis. Suppression of GSH with buthionine sulphoximine administration could deteriorate the fumarate inhibition-mediated tubule injury recovery. Reactive oxygen species/NF-κB signaling activation played a vital role in fumarate-mediated tubule injury. CONCLUSION: Our studies demonstrated that the mitochondrial-derived fumarate promotes tubular epithelial cell injury in renal I/RI. Blockade of fumarate-mediated ROS/NF-κB signaling activation may serve as a novel therapeutic approach to ameliorate hypoxic tubule injury.

A Nutrient-Deficient Microenvironment Facilitates Ferroptosis Resistance via the FAM60A-PPAR Axis in Pancreatic Ductal Adenocarcinoma.

Ferroptosis, a nonapoptotic form of cell death, is an emerging potential therapeutic target for various diseases, including cancer. However, the role of ferroptosis in pancreatic cancer remains poorly understood. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis and chemotherapy resistance, attributed to its high Kirsten rats arcomaviral oncogene homolog mutation rate and severe nutritional deficits resulting from a dense stroma. Several studies have linked rat sarcoma (RAS) mutations to ferroptosis, suggesting that inducing ferroptosis may be an effective strategy against oncogenic RAS-bearing tumors. We investigated the role of Family With Sequence Similarity 60 Member A (FAM60A) in this study, a protein closely associated with a poor prognosis and highly expressed in PDAC and tumor tissue from KrasG12D/+;Trp53R172H/+; Pdx1-Cre mice, in regulating ferroptosis, tumor growth, and gemcitabine sensitivity in vitro and in vivo. Our results demonstrate that FAM60A regulates 3 essential metabolic enzymes, ACSL1/4 and GPX4, to protect PDAC cells from ferroptosis. Furthermore, we found that YY1 transcriptionally regulates FAM60A expression by promoting its transcription, and the Hippo-YY1 pathway is restricted in the low-amino-acid milieu in the context of nutrient deprivation, leading to downstream suppression of peroxisome proliferator-activated receptor and ACSL1/4 and activation of GPX4 pathways. Importantly, FAM60A knockdown sensitized PDAC cells to gemcitabine treatment. A new understanding of FAM60A transcriptional regulation pattern in PDAC and its dual function in ferroptosis reliever and chemotherapy resistance is provided by our study. Targeting FAM60A may therefore offer a promising therapeutic approach for PDAC by simultaneously addressing 2 major features of the disease (high RAS mutation rate and tumor microenvironment nutrient deficiency) and preventing tumor cell metabolic adaptation.

Clinicopathological, immunohistochemical and molecular features of acinic cell carcinoma of the breast.

Breast acinic cell carcinoma (ACC) is a rare subtype of breast cancer. Accurate diagnosis of ACC using core needle biopsy (CNB) is pivotal for the use of effective treatments and patient prognosis. In the present study, a detailed analysis of the morphological, immunohistochemical and gene mutation features of 2 cases of ACC was performed. CNB was performed prior to surgical excision. The breast ACC in the present cases exhibited overt burrowing labyrinthine networks or 'hand-holding-hand' features. The tumor cells in both of the present cases expressed cytokeratin (CK)7, S100 and CK5/6, but were negative for p63, estrogen receptor and progesterone receptor. GATA binding protein 3 was positive in case 1 but negative in case 2. Fluorescence in situ hybridization indicated no ETS variant transcription factor 6 break-apart probe detection. Next-generation sequencing results revealed the same mutation and a similar abundance in exon 27 (NM_005120.2; c.3817G>T; p.A1273S) of the mediator of RNA polymerase II transcription, subunit 12 homolog (MED12) gene in both patients. To conclude, the findings of the present study suggested that recognition of this rare 'hand-holding-hand' structure could potentially be beneficial for avoiding patient misdiagnosis. In addition, it could be suggested that a mutation in the MED12 exon 27 was associated with the formation of a burrowing labyrinthine network or 'hand-holding-hand' feature.

Prevalence of small vessel disease and incidental DWI-positive lesions in patients with aneurysmal subarachnoid hemorrhage versus intracerebral hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) and intracerebral hemorrhage (ICH) are main forms of hemorrhagic stroke. Data regarding cerebral small vessel disease (SVD) burden and incidental small lesions on diffusion-weighted imaging (DWI) following aSAH are sparse. PATIENTS AND METHODS: We retrospectively analyzed a prospective cohort of aSAH and ICH patients with brain MRI within 30 days after onset from March 2015 to January 2023. White matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed (CMB), total SVD score, and incidental DWI lesions were assessed and compared between aSAH and ICH. Clinical and radiological characteristics associated with small DWI lesions in aSAH were investigated. RESULTS: We included 180 patients with aSAH (median age [IQR] 53 [47-61] years) and 299 with ICH (63 [53-73] years). DWI lesions were more common in aSAH than ICH (47.8% vs 14.4%, p < 0.001). Higher total SVD score was associated with ICH versus aSAH irrespective of hematoma location, whereas DWI lesions and strictly lobar CMBs were correlated with aSAH. Multivariable analysis showed that shorter time from onset to MRI, anterior circulation aneurysm rupture, CMB ⩾ 5, and total SVD score were associated with DWI lesions in aSAH. DISCUSSION AND CONCLUSION: Incidental DWI lesions and strictly lobar CMBs were more frequent in aSAH versus ICH whereas ICH had higher SVD burden. Incidental DWI lesions in aSAH were associated with multiple clinical and imaging factors. Longitudinal studies to investigate the dynamic change and prognostic value of the covert hemorrhagic and ischemic lesions in aSAH seem justified.

Clinical, Imaging Characteristics and Outcome of Intracerebral Hemorrhage Caused by Structural Vascular Lesions.

BACKGROUND: The objective of this study was to investigate the clinical, imaging, and outcome characteristics of intracerebral hemorrhage (ICH) caused by structural vascular lesions. METHODS: We retrospectively analyzed data from a prospective observational cohort study of patients with spontaneous ICH admitted to the First Affiliated Hospital of Chongqing Medical University between May 2016 and April 2021. Good outcome was defined as modified Rankin Scale score of 0-3 at 3 months. The clinical and imaging characteristics were compared between primary ICH and ICH caused by structural vascular lesions. Multivariable logistic regression analysis was performed to test the associations of etiology with clinical outcome. RESULTS: All patients enrolled in this study were Asian. Compared with patients with primary ICH, those with structural vascular lesions were younger (48 vs. 62 years, P < 0.001), had a lower incidence of hypertension (26.4% vs. 81.7%, P < 0.001) and diabetes (7.4% vs. 16.2%, P = 0.003), and had mostly lobar hemorrhages (49.1% vs. 22.8%). ICH from structural vascular lesions had smaller baseline hematoma volume (8.4 ml vs. 13.8 ml, P = 0.010), had lower mortality rate at 30 days and 3 months (5.8% vs. 12.0%, P = 0.020; 6.7% vs. 14.8%, P = 0.007), and are associated with better functional outcome at 3 months (88% vs.70.3%, P < 0.001). CONCLUSIONS: Compared with primary ICH, ICH due to vascular lesions has smaller hematoma volume and less severe neurological deficit at presentation and better functional outcomes.

Impact of early cognitive impairment on outcome trajectory in patients with intracerebral hemorrhage.

OBJECTIVE: To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short-term recovery trajectories among ICH patients with early cognitive impairment. METHODS: We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini-mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. RESULTS: Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1-year increase, 1.037; 95% confidence interval [CI], 1.003-1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1-point increase, 1.146; 95% CI, 1.065-1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810-12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133-0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503-12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). INTERPRETATION: Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short-term functional recovery.

Micro-elimination of hepatitis C virus infection in the hemodialysis population / 临床肝胆病杂志

The hemodialysis population is increasing year by year in China. Due to the specific nature of hemodialysis treatment， the prevalence and incidence rates of hepatitis C virus （HCV） infection in hemodialysis patients are much higher than the general population. In order to achieve the WHO’s initiative to eliminate HCV by 2030 and realize the micro-elimination of HCV in the hemodialysis population， standard infection control and hand hygiene procedures should be implemented to cut off the route of iatrogenic infection， especially to prevent the outbreak of HCV infection in hemodialysis centers. Screening for HCV infection should be conducted for patients newly admitted to the hemodialysis center or transferred to another hemodialysis center， and regular screening should be conducted for patients receiving maintenance hemodialysis to identify new HCV infections in the early stage. It is also necessary to collaborate with specialists and provide direct-acting antiviral therapy for hemodialysis patients with HCV infection.