Deubiquitinase USP18 inhibits hepatic stellate cells activation and alleviates liver fibrosis via regulation of TAK1 activity.

BACKGROUND & AIMS: Activation of hepatic stellate cells (HSCs) is the key process underlying liver fibrosis. Unveiling its molecular mechanism may provide an effective target for inhibiting liver fibrosis. Protein ubiquitination is a dynamic and reversible process. Deubiquitinases (DUBs) catalyze the removal of ubiquitin chains from substrate proteins, thereby inhibiting the biological processes regulated by ubiquitination signals. However, there are few studies revealing the role of deubiquitination in the activation of HSCs. METHODS & RESULTS: Single-cell RNA sequencing (scRNA-seq) revealed significantly decreased USP18 expression in activated HSCs when compared to quiescent HSCs. In mouse primary HSCs, continuous activation of HSCs led to a gradual decrease in USP18 expression whilst restoration of USP18 expression significantly inhibited HSC activation. Injection of USP18 lentivirus into the portal vein of a CCl4-induced liver fibrosis mouse model confirmed that overexpression of USP18 can significantly reduce the degree of liver fibrosis. In terms of mechanism, we screened some targets of USP18 in mouse primary HSCs and found that USP18 could directly bind to TAK1. Furthermore, we demonstrated that USP18 can inhibit TAK1 activity by interfering with the K63 ubiquitination of TAK1. CONCLUSIONS: Our study demonstrated that USP18 inhibited HSC activation and alleviated liver fibrosis via modulation of TAK1 activity; this may prove to be an effective target for inhibiting liver fibrosis.

Genome-wide sRNA and mRNA transcriptomic profiling insights into carbapenem-resistant Acinetobacter baumannii.

Introduction: Acinetobacter baumannii (AB) is rising as a human pathogen of critical priority worldwide as it is the leading cause of opportunistic infections in healthcare settings and carbapenem-resistant AB is listed as a "super bacterium" or "priority pathogen for drug resistance" by the World Health Organization. Methods: Clinical isolates of A. baumannii were collected and tested for antimicrobial susceptibility. Among them, carbapenem-resistant and carbapenem-sensitive A. baumannii were subjected to prokaryotic transcriptome sequencing. The change of sRNA and mRNA expression was analyzed by bioinformatics and validated by quantitative reverse transcription-PCR. Results: A total of 687 clinical isolates were collected, of which 336 strains of A. baumannii were resistant to carbapenem. Five hundred and six differentially expressed genes and nineteen differentially expressed sRNA candidates were discovered through transcriptomic profile analysis between carbapenem-resistant isolates and carbapenem-sensitive isolates. Possible binding sites were predicted through software for sRNA21 and adeK, sRNA27 and pgaC, sRNA29 and adeB, sRNA36 and katG, indicating a possible targeting relationship. A negative correlation was shown between sRNA21 and adeK (r = -0.581, P = 0.007), sRNA27 and pgaC (r = -0.612, P = 0.004), sRNA29 and adeB (r = -0.516, P = 0.020). Discussion: This study preliminarily screened differentially expressed mRNA and sRNA in carbapenem-resistant A. baumannii, and explored possible targeting relationships, which will help further reveal the resistance mechanism and provide a theoretical basis for the development of drugs targeting sRNA for the prevention and treatment of carbapenem-resistant A. baumannii infection.

Computational identification of novel potential genetic pathogenesis and otherwise biomarkers in acute liver allograft rejection.

Acute cellular rejection (ACR) is a prevalent postoperative complication following liver transplantation (LT), exhibiting an increasing incidence of morbidity and mortality. However, the molecular mechanisms of ACR following LT remain unclear. To explore the genetic pathogenesis and identify biomarkers of ACR following LT, three relevant Gene Expression Omnibus (GEO) datasets consisting of data on ACR or non-ACR patients after LT were comprehensively investigated by computational analysis. A total of 349 upregulated and 260 downregulated differentially expressed genes (DEGs) and eight hub genes (ISG15, HELZ2, HNRNPK, TIAL1, SKIV2L2, PABPC1, SIRT1, and PPARA) were identified. Notably, HNRNPK, TIAL1, and PABPC1 exhibited the highest predictive potential for ACR with AUCs of 0.706, 0.798, and 0.801, respectively. KEGG analysis of hub genes revealed that ACR following LT was predominately associated with ferroptosis, protein processing in the endoplasmic reticulum, complement and coagulation pathways, and RIG-I/NOD/Toll-like receptor signaling pathway. According to the immune cell infiltration analysis, γδT cells, NK cells, Tregs, and M1/M2-like macrophages had the highest levels of infiltration. Compared to SIRT1, ISG15 was positively correlated with γδT cells and M1-like macrophages but negatively correlated with NK cells, CD4+ memory T cells, and Tregs. In conclusion, this study identified eight hub genes and their potential pathways, as well as the immune cells involved in ACR following LT with the greatest levels of infiltration. These findings provide a new direction for future research on the underlying mechanism of ACR following LT.

Carbon capture in power sector of China towards carbon neutrality and its comparison to renewable power.

CO2 capture from coal power plants is an important and necessary solution to realizing carbon neutrality in China, but CCS demonstration deployment in power sector is far behind expectations. Hence, the reduction potential of energy consumption and cost for CCS and its competitiveness to renewable powers are very important to make roadmaps and policies toward carbon neutrality. Unlike the popular recognition that capturing CO2 from flue gases is technically and commercially mature, this paper notes that it has been proved to be technically feasible but far beyond technology maturity and high energy penalty leads to its immaturity and therefore causes high cost. Additionally, the potential energy penalty reduction of capture is investigated thermodynamically, and future CO2 avoidance cost is predicted and compared to renewable power (solar PV and onshore wind power). Results show that energy penalty for CO2 capture can be reduced by 48%-57%. When installation capacity reaches a similar scale to that of solar PV in China (250 GW), CO2 capture cost in coal power plants can be reduced from the current 28-40 US$/ton to 10-20 US$/ton, and efficiency upgrade contributes to 67%-75% in cost reduction for high coal price conditions. In China, CO2 capture in coal power plants can be cost competitive with solar PV and onshore wind power. But it is worth noting that the importance and share of CCS role in CO2 emission reduction is decreasing since renewable power is already well deployed and there is still a lack of large-scale CO2 capture demonstrations in China. Innovative capture technologies with low energy penalties need to be developed to promote CCS. Results in this work can provide informative references for making roadmaps and policies regarding CO2 emission reductions that contribute towards carbon neutrality.

[Causes of missed diagnosis of clinically significant prostate cancer by targeted biopsy].

OBJECTIVE: To retrospectively analyze the causes of missed diagnosis of clinically significant PCa (csPCa) by targeted biopsy (TB). METHODS: This retrospective study included 652 males aged (71.32 ± 16.53) years with elevated PSA and abnormal MRI signals detected in our hospital from June 2018 to December 2020. We further examined the patients by transperineal prostatic TB and systematic biopsy (SB), analyzed the detection rates of PCa and csPCa by TB and SB, and investigated the causes of missed diagnosis of csPCa in TB using the fishbone diagram. RESULTS: The total detection rate of PCa and csPCa by TB combined with SB was 45.7% (298/652), and that of csPCa was 37.4% (244/652), with 38 cases of csPCa missed in TB, including 23 cases of negative TB and 15 cases of low ISUP grade. The causes of missed diagnosis of csPCa by TB included low MRI image quality, PSA density ≤0.15 ng/ml/cm3, target area <10 mm, and PI-RADS 2 score ≤3. The detection rate of csPCa by TB alone was 31.6%, which was increased by 5.8% (P = 0.027) when TB combined with SB. CONCLUSION: TB combined with SB yields a higher detection rate of csPCa than either used alone. Missed diagnosis of csPCa by TB is closely related to the characteristics of tumor and MR image of the target area.

Mito-LND and (E)-Akt inhibitor-IV: novel compounds inducing endoplasmic reticulum stress and ROS accumulation against hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. Although multi-kinase inhibitors can prolong the overall survival of late-stage HCC patients, the emergence of drug resistance diminishes these benefits, ultimately resulting in treatment failure. Therefore, there is an urgent need for novel and effective drugs to impede the progression of liver cancer. METHODS: This study employed a concentration gradient increment method to establish acquired sorafenib or regorafenib-resistant SNU-449 cells. Cell viability was assessed using the cell counting kit-8 assay. A library of 793 bioactive small molecules related to metabolism screened compounds targeting both parental and drug-resistant cells. The screened compounds will be added to both the HCC parental cells and the drug-resistant cells, followed by a comprehensive assessment. Intracellular adenosine triphosphate (ATP) levels were quantified using kits. Flow cytometry was applied to assess cell apoptosis and reactive oxygen species (ROS). Real-time quantitative PCR studied relative gene expression, and western blot analysis assessed protein expression changes in HCC parental and drug-resistant cells. A xenograft model in vivo evaluated Mito-LND and (E)-Akt inhibitor-IV effects on liver tumors, with hematoxylin and eosin staining for tissue structure and immunohistochemistry staining for endoplasmic reticulum stress protein expression. RESULTS: From the compound library, we screened out two novel compounds, Mito-LND and (E)-Akt inhibitor-IV, which could potently kill both parental cells and drug-resistant cells. Mito-LND could significantly suppress proliferation and induce apoptosis in HCC parental and drug-resistant cells by upregulating glycolytic intermediates and downregulating those of the tricarboxylic acid (TCA) cycle, thereby decreasing ATP production and increasing ROS. (E)-Akt inhibitor-IV achieved comparable results by reducing glycolytic intermediates, increasing TCA cycle intermediates, and decreasing ATP synthesis and ROS levels. Both compounds trigger apoptosis in HCC cells through the interplay of the AMPK/MAPK pathway and the endoplasmic reticulum stress response. In vivo assays also showed that these two compounds could significantly inhibit the growth of HCC cells and induce endoplasmic reticulum stress. CONCLUSION: Through high throughput screening, we identified that Mito-LND and (E)-Akt inhibitor-IV are two novel compounds against both parental and drug-resistant HCC cells, which could offer new strategies for HCC patients.

Selectively lighting up glyoxal in living cells using an o-phenylenediamine fused hemicyanine.

Glyoxal (GL) is a reactive α-dicarbonyl compound generated from glycated proteins in the Maillard reaction. It has attracted particular attention over the past few years because of its possible clinical significance in chronic and age-related diseases. In this work, a reaction-based red emission fluorescent probe GL1 has been synthesized successfully by grafting an alkyl group onto an amino group to regulate its selectivity for GL. Under physiological conditions, the fluorescence intensity of GL1 at 640 nm obviously increased with the increase of GL concentration, and it exhibited high selectivity for GL over other reactive carbonyl compounds, as well as a lower detection limit (0.021 µM) and a larger Stokes shift (112 nm). At the same time, GL1 can selectively accumulate in mitochondria and can be used to detect exogenous and endogenous GL in living cells with low cytotoxicity.

Deep active learning with high structural discriminability for molecular mutagenicity prediction.

The assessment of mutagenicity is essential in drug discovery, as it may lead to cancer and germ cells damage. Although in silico methods have been proposed for mutagenicity prediction, their performance is hindered by the scarcity of labeled molecules. However, experimental mutagenicity testing can be time-consuming and costly. One solution to reduce the annotation cost is active learning, where the algorithm actively selects the most valuable molecules from a vast chemical space and presents them to the oracle (e.g., a human expert) for annotation, thereby rapidly improving the model's predictive performance with a smaller annotation cost. In this paper, we propose muTOX-AL, a deep active learning framework, which can actively explore the chemical space and identify the most valuable molecules, resulting in competitive performance with a small number of labeled samples. The experimental results show that, compared to the random sampling strategy, muTOX-AL can reduce the number of training molecules by about 57%. Additionally, muTOX-AL exhibits outstanding molecular structural discriminability, allowing it to pick molecules with high structural similarity but opposite properties.

Odor Fingerprinting of Chitosan and Source Identification of Commercial Chitosan: HS-GC-IMS, Multivariate Statistical Analysis, and Tracing Path Study.

Chitosan samples were prepared from the shells of marine animals (crab and shrimp) and the cell walls of fungi (agaricus bisporus and aspergillus niger). Fourier-transform infrared spectroscopy (FT-IR) was used to detect their molecular structures, while headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) was employed to analyze their odor composition. A total of 220 volatile organic compounds (VOCs), including esters, ketones, aldehydes, etc., were identified as the odor fingerprinting components of chitosan for the first time. A principal component analysis (PCA) revealed that chitosan could be effectively identified and classified based on its characteristic VOCs. The sum of the first three principal components explained 87% of the total variance in original information. An orthogonal partial least squares discrimination analysis (OPLS-DA) model was established for tracing and source identification purposes, demonstrating excellent performance with fitting indices R2X = 0.866, R2Y = 0.996, Q2 = 0.989 for independent variable fitting and model prediction accuracy, respectively. By utilizing OPLS-DA modeling along with a heatmap-based tracing path study, it was found that 29 VOCs significantly contributed to marine chitosan at a significance level of VIP > 1.00 (p < 0.05), whereas another set of 20 VOCs specifically associated with fungi chitosan exhibited notable contributions to its odor profile. These findings present a novel method for identifying commercial chitosan sources, which can be applied to ensure biological safety in practical applications.

Thromboelastography-Guided Antiplatelet Therapy for Patients with Ischemic Cerebrocardiovascular Diseases: A Systematic Review and Meta-Analysis.

INTRODUCTION: The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. METHODS: Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. RESULTS: Ten studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR: 0.45, 95% CI: 0.27-0.75, p = 0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR: 0.26, 95% CI: 0.19-0.37; p < 0.00001), ischemic events (OR: 0.28, 95% CI: 0.19-0.41; p < 0.00001), and bleeding events (OR: 0.31, 95% CI: 0.16-0.62; p = 0.0009) in patients with IS or CAD. CONCLUSION: TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.

Constructibility of AdS Supergluon Amplitudes.

We prove that all tree-level n-point supergluon (scalar) amplitudes in AdS_{5} can be recursively constructed, using factorization and flat-space limit. Our method is greatly facilitated by a natural R-symmetry basis for planar color-ordered amplitudes, which reduces the latter to "partial amplitudes" with simpler pole structures and factorization properties. Given the n-point scalar amplitude, we first extract spinning amplitudes with n-2 scalars and one gluon by imposing "gauge invariance," and then use a special "no-gluon kinematics" to determine the (n+1)-point scalar amplitude completely (which in turn contains the n-point single-gluon amplitude). Explicit results of up to 8-point scalar amplitudes and up to 6-point single-gluon amplitudes are included as Supplemental Material.

Dual antiplatelet therapy for ischemic stroke with intracranial arterial stenosis: a systematic review and meta-analysis.

Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious. Aims: This study evaluates DAPT's effectiveness and safety for these patients. Methods: This review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4. Results: Analysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46-0.59, p < 0.001) and recurrent stroke (RR = 0.37; 95% CI: 0.30-0.44, p < 0.001) compared to SAPT. There was no significant increase in bleeding events (RR = 1.34; 95% CI: 0.97-1.85, p = 0.07) or cerebral hemorrhage (RR = 0.47; 95% CI: 0.17-1.31, p = 0.15). Conclusion: DAPT proveed to be effective and safe for ischemic stroke patients with ICAS and significantly reduced stroke and the composite endpoint of ischemic and bleeding events without elevating bleeding risks.

PCSK9 inhibitor added to high-intensity statin therapy to prevent cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention: a randomized, double- blind, placebo-controlled, multicenter SHAWN study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

A highly sensitive ratiometric fluorescence probe for sensing and imaging sulfite in food samples and living cells.

In this work, a ratiometric and chromogenic fluorescent probe 1 was synthesized for the detection of SO32-. The probe 1 at PBS (10 mM, pH = 7.4) presented a marked emission band at 661 nm. Upon addition of SO32- ions, a highly emissive adduct with a marked fluorescence at 471 nm were obtained through a Michael addition. The probe 1 displayed a noticeable fluorescence ratiometric response with a large shift (190 nm) in emission wavelength. The probe can quantitatively detect SO32- with high specificity, fast response (within 130 s) as well as low detection limit (13 nM), and a large Stokes shift (139 nm). Fluorescence imaging of HeLa cells indicated that 1 could be used for monitoring the intrinsically generated intracellular SO32- in living cells by ratiometric fluorescence imaging. Furthermore, 1 could be application in real water and sugar samples with high sensitivity and good recoveries.

Current treatment of biliary Sphincter of Oddi Dysfunction.

The sphincter of Oddi is a delicate neuromuscular structure located at the junction of the biliary-pancreatic system and the duodenum. Sphincter of Oddi Dysfunction (SOD) can result in various clinical manifestations, including biliary-type pain and recurrent idiopathic pancreatitis. The management of SOD has been challenging. With the publication of the landmark Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial and the Rome IV consensus, our clinical practice in the treatment of SOD has changed significantly in recent years. Currently, the management of type II SOD remains controversial and there is a lack of non-invasive therapy options, particularly for patients not responding to endoscopic treatment. In this mini review, we aimed to discuss the current knowledge on the treatment of biliary SOD.

Re-discovery and taxonomic clarification of Oreocharisleveilleana (Gesneriaceae) in Guizhou, China, over 100 years.

Oreocharisleveilleana Fedde was collected in Ta-pin in 1910 and published in 1911. The collected location was verified within western Luodian County, Guizhou Province, China. However, there have been no records of the species' collection for more than 100 years since then. After extensive investigations by our research team on the type locality and its surrounding areas, we found that it is widely distributed in western Luodian County and eastern Wangmo County, Guizhou Province, China. During further research on the original literature, type specimens and type locality of O.leveilleana, the taxonomic position of O.leveilleana, which was once treated as a synonym of O.auricula (S.Moore) C.B.Clarke, was found to have a taxonomic problem. Through morphological research combined with geographical distribution analysis, it has been determined that it should belong to the genus Petrocodon Hance and it is the same species as P.coccineus (C.Y.Wu ex H.W.Li) Yin Z.Wang. According to the regulations and suggestions of the 2018 "International Code of Nomenclature for Algae, Fungi, and Plants (Shenzhen Code)", we propose and confirm a new combination - Petrocodonleveilleanus (Fedde) X.X.Bai & F.Wen and treat P.coccineus as a synonym of the new combination. Due to its unique bright red flowers within Petrocodon, its original Chinese name has been retained.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Case report: Primary myelofibrosis presenting with portal hypertension mimicking cirrhosis.

Primary myelofibrosis (PMF) is an infrequent etiology of noncirrhotic portal hypertension (PH). In clinical settings, non-cirrhotic PH is often misdiagnosed as cirrhotic PH. This case report details a patient who exhibited recurrent esophageal variceal hemorrhage and was initially misdiagnosed with cirrhosis. Initially poised for liver transplantation, the patient's liver biopsy revealed no significant cirrhosis but showed signs of extramedullary hematopoiesis (EMH). Following the accurate diagnosis of PMF, the patient underwent standard treatment, leading to an absence of recurrent gastrointestinal hemorrhage due to esophageal varices for nearly three years.

Clinical prediction factors of nonchronic total occlusion lesion progression in patients with unstable angina receiving percutaneous coronary intervention for chronic total occlusion lesions.

Background: In this study, we investigated clinical prediction factors of nonchronic total occlusion lesion (NCTOL) progression in patients who underwent percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions. Methods: In total, 450 patients with unstable angina (mean age = 57.1 ± 9.2 years) who underwent PCI for CTO lesions between January 2016 and December 2018 at Beijing Anzhen Hospital were enrolled in this study. A clinical and angiographic follow-up examination was performed 12 months postoperatively. The patients were divided into NCTOL progression (145 cases) and control (305 cases) groups based on the outcome of the 12-month angiographic follow-up. The clinical and angiographic features of the participants were analyzed. Results: The adenosine diphosphate-induced platelet aggregation (ADP-IPA) rate and levels of lipoprotein (a) (Lp(a)) in the NCTOL progression group were significantly higher than those in the control group (51.89 ± 14.81 vs. 39.63 ± 17.12, P < 0.01; 0.22 ± 0.26 vs. 0.14 ± 0.18, P < 0.05, respectively). Logistic regression showed that the ADP-IPA rate (odds ratio = 1.047, 95 % confidence interval: 1.014-1.082, P = 0.005) and Lp(a) (odds ratio = 11.972, 95 % confidence interval: 1.230-116.570, P = 0.033) were independent predictors of NCTOL progression. Partial correlation analysis demonstrated that the ADP-IPA rate was positively correlated with NCTOL progression (r = 0. 351, P < 0.001). Receiver operating characteristic curve showed that the boundary point of the ADP-IPA rate to predict NCTOL progression was 30 % (sensitivity, 86.2 %; specificity, 68.9 %). Conclusions: NCTOL progression is an important cause of recurrent PCI in patients with coronary artery disease after PCI for CTO lesions. The ADP-IPA rate is a useful predictor for NCTOL progression in patients with unstable angina who undergo PCI for CTO lesions.