Formulating N-Doped Carbon Hollow Nanospheres with Highly Accessible Through-Pores to Isolate Fe Single-Atoms for Efficient Oxygen Reduction.

It is challenging yet promising to design highly accessible N-doped carbon skeletons to fully expose the active sites inside single-atom catalysts. Herein, mesoporous N-doped carbon hollow spheres with regulatable through-pore size can be formulated by a simple sequential synthesis procedure, in which the condensed SiO2 is acted as removable dual-templates to produce both hollow interiors and through-pores, meanwhile, the co-condensed polydopamine shell is served as N-doped carbon precursor. After that, Fe─N─C hollow spheres (HSs) with highly accessible active sites can be obtained after rationally implanting Fe single-atoms. Microstructural analysis and X-ray absorption fine structure analysis reveal that high-density Fe─N4 active sites together with tiny Fe clusters are uniformly distributed on the mesoporous carbon skeleton with abundant through-pores. Benefitted from the highly accessible Fe─N4 active sites arising from the unique through-pore architecture, the Fe─N─C HSs demonstrate excellent oxygen reduction reaction (ORR) performance in alkaline media with a half-wave potential up to 0.90 V versus RHE and remarkable stability, both exceeding the commercial Pt/C. When employing Fe─N─C HSs as the air-cathode catalysts, the assembled Zn-air batteries deliver a high peak power density of 204 mW cm-2 and stable discharging voltage plateau over 140 h.

Low-Potential Iodide Oxidation Enables Dual-Atom CoFe─N─C Catalysts for Ultra-Stable and High-Energy-Efficiency Zn-Air Batteries.

The low energy efficiency and limited cycling life of rechargeable Zn-air batteries (ZABs) arising from the sluggish oxygen reduction/evolution reactions (ORR/OERs) severely hinder their commercial deployment. Herein, a zeolitic imidazolate framework (ZIF)-derived strategy associated with subsequent thermal fixing treatment is proposed to fabricate dual-atom CoFe─N─C nanorods (Co1 Fe1 ─N─C NRs) containing atomically dispersed bimetallic Co/Fe sites, which can promote the energy efficiency and cyclability of ZABs simultaneously by introducing the low-potential oxidation redox reactions. Compared to the mono-metallic nanorods, Co1 Fe1 ─N─C NRs exhibit remarkable ORR performance including a positive half-wave potential of 0.933 V versus reversible hydrogen electrode (RHE) in alkaline electrolyte. Surprisingly, after introducing the potassium iodide (KI) additive, the oxidation overpotential of Co1 Fe1 ─N─C NRs to reach 10 mA cm-2 can be significantly reduced by 395 mV compared to the conventional destructive OER. Theoretical calculations show that the markedly decreased overpotential of iodide oxidation can be ascribed to the synergistic effects of neighboring Co─Fe diatomic sites as the unique adsorption sites. Overall, aqueous ZABs assembled with Co1 Fe1 ─N─C NRs and KI as the air-cathode catalyst and electrolyte additive, respectively, can deliver a low charging voltage of 1.76 V and ultralong cycling stability of over 230 h with a high energy efficiency of ≈68%.

A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Development and validation of a prognostic model for 90-day survival in patients with alcohol-associated cirrhosis and acute decompensation.

BACKGROUND/PURPOSE: Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression. METHODS: We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90-day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C-index, area under the receiver operating curve, calibration curve, and decision curve analysis. RESULTS: Total bilirubin >10 upper limit of normal, high-density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90-day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C-index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high- and low-risk groups. Mortality was significantly higher in the high-risk group than in the low-risk group (p < 0.0001). CONCLUSION: The nomogram could accurately predict the 90-day mortality risk in patients with alcohol-associated cirrhosis and acute decompensation, helping to identify high-risk patients and personalize treatment at their first admission.

Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

Enantioselective formal total synthesis of dihydrospirotryprostatin B.

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

A combined diagnostic model based on circulating tumor cell in patients with solitary pulmonary nodules.

BACKGROUND: Although many prediction models in diagnosis of solitary pulmonary nodules (SPNs) have been developed, few are widely used in clinical practice. It is therefore imperative to identify novel biomarkers and prediction models supporting early diagnosis of SPNs. This study combined folate receptor-positive circulating tumor cells (FR+ CTC) with serum tumor biomarkers, patient demographics and clinical characteristics to develop a prediction model. METHODS: A total of 898 patients with a solitary pulmonary nodule who received FR+ CTC detection were randomly assigned to a training set and a validation set in a 2:1 ratio. Multivariate logistic regression was used to establish a diagnostic model to differentiate malignant and benign nodules. The receiver operating curve (ROC) and the area under the curve (AUC) were calculated to assess the diagnostic efficiency of the model. RESULTS: The positive rate of FR+ CTC between patients with non-small cell lung cancer (NSCLC) and benign lung disease was significantly different in both the training and the validation dataset (p < 0.001). The FR+ CTC level was significantly higher in the NSCLC group compared with that of the benign group (p < 0.001). FR+ CTC (odds ratio, OR, 95% confidence interval, CI: 1.13, 1.07-1.19, p < 0.0001), age (OR, 95% CI: 1.06, 1.01-1.12, p = 0.03) and sex (OR, 95% CI: 1.07, 1.01-1.13, p = 0.01) were independent risk factors of NSCLC in patients with a solitary pulmonary nodule. The area under the curve (AUC) of FR+ CTC in diagnosing NSCLC was 0.650 (95% CI, 0.587-0.713) in the training set and 0.700 (95% CI, 0.603-0.796) in the validation set, respectively. The AUC of the combined model was 0.725 (95% CI, 0.659-0.791) in the training set and 0.828 (95% CI, 0.754-0.902) in the validation set, respectively. CONCLUSIONS: We confirmed the value of FR+ CTC in diagnosing SPNs and developed a prediction model based on FR+ CTC, demographic characteristics, and serum biomarkers for differential diagnosis of solitary pulmonary nodules.

Self-Sacrificing Template Synthesis of Carbon Nanosheets Assembled Hollow Spheres with Abundant Active Fe-N4 O1 Moieties for Electrocatalytic Oxygen Reduction.

Single-atom Fe-N-C (Fe1 -N-C) materials represent the benchmarked electrocatalysts for oxygen reduction reaction (ORR). However, single Fe atoms in the carbon skeletons cannot be fully utilized due to the mass transfer limitation, severely restricting their intrinsic ORR properties. Herein, a self-sacrificing template strategy is developed to fabricate ultrathin nanosheets assembled Fe1 -N-C hollow microspheres (denoted as Fe1 /N-HCMs) by rational carbonization of Fe3+ chelating polydopamine coated melamine cyanuric acid complex. The shell of Fe1 /N-HCMs is constructed by ultrathin nanosheets with thickness of only 2 nm, which is supposed to be an ideal platform to isolate and fully expose single metal atoms. Benefiting from unique hierarchical hollow architecture with highly open porous structure, 2 nm-thick ultrathin nanosheet subunits and abundant Fe-N4 O1 active sites revealed by X-ray absorption fine structure analysis, the Fe1 /N-HCMs exhibit high ORR performance with a positive half-wave potential of 0.88 V versus the reversible hydrogen electrode and robust stability. When served as air-cathode catalysts with ultralow loading mass of 0.25 mg cm-2 , Fe1 /N-HCMs based Zn-air batteries present a maximum power density of 187 mW cm-2 and discharge specific capacity of 806 mA h gZn -1 in primary Zn-air batteries, all exceeding those of commercial Pt/C.

Assessment of arterial-phase hyperenhancement and late-phase washout of hepatocellular carcinoma-a meta-analysis of contrast-enhanced ultrasound (CEUS) with SonoVue® and Sonazoid®.

OBJECTIVES: The recognition of arterial phase hyperenhancement (APHE) and washout during the late phase is key for correct diagnosis of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS). This meta-analysis was conducted to compare SonoVue®-enhanced and Sonazoid®-enhanced ultrasound in the assessment of HCC enhancement and diagnosis. METHODS: Studies were included in the analysis if they reported data for HCC enhancement in the arterial phase and late phase for SonoVue® or in the arterial phase and Kupffer phase (KP) for Sonazoid®. Forty-two studies (7502 patients) with use of SonoVue® and 30 studies (2391 patients) with use of Sonazoid® were identified. In a pooled analysis, the comparison between SonoVue® and Sonazoid® CEUS was performed using chi-square test. An inverse variance weighted random-effect model was used to estimate proportion, sensitivity, and specificity along with 95% confidence interval (CI). RESULTS: In the meta-analysis, the proportion of HCC showing APHE with SonoVue®, 93% (95% CI 91-95%), was significantly higher than the proportion of HCC showing APHE with Sonazoid®, 77% (71-83%) (p < 0.0001); similarly, the proportion of HCC showing washout at late phase/KP was significantly higher with SonoVue®, 86% (83-89%), than with Sonazoid®, 76% (70-82%) (p < 0.0001). The sensitivity and specificity for the detection of APHE plus late-phase/KP washout detection in HCC were also higher with SonoVue® than with Sonazoid® (sensitivity 80% vs 52%; specificity 80% vs 73% in studies within unselected patient populations). CONCLUSION: APHE and late washout in HCC are more frequently observed with SonoVue® than with Sonazoid®. This may affect the diagnostic performance of CEUS in the diagnosis of HCCs. CLINICAL RELEVANCE STATEMENT: Meta-analysis data show the presence of key enhancement features for diagnosis of hepatocellular carcinoma is different between ultrasound contrast agents, and arterial hyperenhancement and late washout are more frequently observed at contrast-enhanced ultrasound with SonoVue® than with Sonazoid®. KEY POINTS: • Dynamic enhancement features are key for imaging-based diagnosis of HCC. • Arterial hyperenhancement and late washout are more often observed in HCCs using SonoVue®-enhanced US than with Sonazoid®. • The existing evidence for contrast-enhanced US may need to be considered being specific to the individual contrast agent.

Synthesis and Structure Revision of Naturally Occurring Homoisoflavane (+)-Dracaeconolide B.

Dracaeconolide B (1), a naturally occurring homoisoflavane, was isolated from the red resin of Dracaena cochinchinensis. Efforts have been made to elucidate the exact structure of compound 1 since it was confirmed that dracaeconolide B did not contain a 7-hydroxy-5,8-dimethoxy moiety. The structure of dracaeconolide B was revised by synthesis of three homoisoflavanes containing a 5,6,7-trioxygenated moiety each and analysis by NMR spectroscopy. The revised structure of dracaeconolide B was proposed as 3-(4-hydroxybenzyl)-7-hydroxy-5,6-dimethoxychromane. Noyori's Ru-catalyzed asymmetric transfer hydrogenation was used to synthesize (+)-dracaeconolide B. The absolute configuration of the compound was revised to S based on the results obtained by the electronic circular dichroism calculation. We examined the antiangiogenic activity of (S)- and (R)-dracaeconolide B and of synthetic 5,6,7- and 5,7,8-trioxygenated homoisoflavanes. The results can potentially help in the synthesis of related natural products and support drug discovery to treat neovascular eye diseases.

A Middle Eocene lowland humid subtropical "Shangri-La" ecosystem in central Tibet.

Tibet's ancient topography and its role in climatic and biotic evolution remain speculative due to a paucity of quantitative surface-height measurements through time and space, and sparse fossil records. However, newly discovered fossils from a present elevation of ∼4,850 m in central Tibet improve substantially our knowledge of the ancient Tibetan environment. The 70 plant fossil taxa so far recovered include the first occurrences of several modern Asian lineages and represent a Middle Eocene (∼47 Mya) humid subtropical ecosystem. The fossils not only record the diverse composition of the ancient Tibetan biota, but also allow us to constrain the Middle Eocene land surface height in central Tibet to ∼1,500 ± 900 m, and quantify the prevailing thermal and hydrological regime. This "Shangri-La"-like ecosystem experienced monsoon seasonality with a mean annual temperature of ∼19 °C, and frosts were rare. It contained few Gondwanan taxa, yet was compositionally similar to contemporaneous floras in both North America and Europe. Our discovery quantifies a key part of Tibetan Paleogene topography and climate, and highlights the importance of Tibet in regard to the origin of modern Asian plant species and the evolution of global biodiversity.

[Research progress on traditional Chinese medicine in treatment of neurodegenerative diseases by delaying neurovascular unit aging].

Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.

Transition Metal (Co, Ni, Fe, Cu) Single-Atom Catalysts Anchored on 3D Nitrogen-Doped Porous Carbon Nanosheets as Efficient Oxygen Reduction Electrocatalysts for Zn-Air Battery.

Exploring highly active and cost-efficient single-atom catalysts (SACs) for oxygen reduction reaction (ORR) is critical for the large-scale application of Zn-air battery. Herein, density functional theory (DFT) calculations predict that the intrinsic ORR activity of the active metal of SACs follows the trend of Co > Fe > Ni ≈ Cu, in which Co SACs possess the best ORR activity due to its optimized spin density. Guided by DFT calculations, four kinds of transition metal single atoms embedded in 3D porous nitrogen-doped carbon nanosheets (MSAs@PNCN, M = Co, Ni, Fe, Cu) are synthesized via a facile NaCl-template assisted strategy. The resulting MSAs@PNCN displays ORR activity trend in lines with the theoretical predictions, and the Co SAs@PNCN exhibits the best ORR activity (E1/2  = 0.851 V), being comparable to that of Pt/C under alkaline conditions. X-ray absorption fine structure (XAFS) spectra verify the atomically dispersed Co-N4 sites are the catalytically active sites. The highly active CoN4 sites and the unique 3D porous structure contribute to the outstanding ORR performance of Co SAs@PNCN. Furthermore, the Co SAs@PNCN catalyst is employed as cathode in Zn-air battery, which can deliver a large power density of 220 mW cm-2 and maintain robust cycling stability over 530 cycles.

Isolating Fe Atoms in N-Doped Carbon Hollow Nanorods through a ZIF-Phase-Transition Strategy for Efficient Oxygen Reduction.

Transition metal-nitrogen-carbon (TM-N-C) catalysts have been intensely investigated to tackle the sluggish oxygen reduction reactions (ORRs), but insufficient accessibility of the active sites limits their performance. Here, by using solid ZIF-L nanorods as self-sacrifice templates, a ZIF-phase-transition strategy is developed to fabricate ZIF-8 hollow nanorods with open cavities, which can be subsequently converted to atomically dispersed Fe-N-C hollow nanorods (denoted as Fe1 -N-C HNRs) through rational carbonization and following fixation of iron atoms. The microstructure observation and X-ray absorption fine structure analysis confirm abundant Fe-N4 active sites are evenly distributed in the carbon skeleton. Thanks to the highly accessible Fe-N4 active sites provided by the highly porous and open carbon hollow architecture, the Fe1 -N-C HNRs exhibit superior ORR activity and stability in alkaline and acidic electrolytes with very positive half-wave potentials of 0.91 and 0.8 V versus RHE, respectively, both of which surpass those of commercial Pt/C. Remarkably, the dynamic current density (JK ) of Fe1 -N-C HNRs at 0.85 V versus RHE in alkaline media delivers a record value of 148 mA cm-2 , 21 times higher than that of Pt/C. The assembled Zn-air battery using Fe1 -N-C HNRs as cathode catalyst exhibits a high peak power density of 208 mW cm-2 .

Plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy induced by type 2 diabetes mellitus.

The glymphatic system is a recently discovered glial-dependent macroscopic interstitial waste clearance system that promotes the efficient elimination of soluble proteins and metabolites from the central nervous system. Its anatomic foundation is the astrocytes and aquaporin-4 (AQP4) water channels on the endfeet of astrocytes. The aim of this study is to evaluate the plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy (PDN) induced by type 2 diabetes mellitus. PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. MRI was applied to observe the infiltration and clearance of contrast to indicate the functional variability of the glymphatic system at the spinal cord level. The paw withdrawal threshold was used to represent mechanical allodynia. The numerical change of glial fibrillary acidic protein (GFAP) positive astrocytes was assessed and the polarity reversal of AQP4 protein was measured by immunofluorescence. As a result, deceased contrast infiltration and clearance, enhanced mechanical allodynia, increased number of GFAP positive astrocytes, and reversed polarity of AQP4 protein were found in the PDN rats. The above molecular level changes may contribute to the impairment of the spinal glymphatic system in PDN rats. This study revealed the molecular and functional variations of the spinal glymphatic system in PDN rats and for the first time indicated that there might be a correlation between the impaired spinal glymphatic system and PDN rats.

Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway.

BACKGROUND: Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs. METHODS: The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model. RESULTS: αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment. CONCLUSION: This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU-induced augmentation of CSCs via the Notch signaling pathway.

Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study.

BACKGROUND & AIMS: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. METHODS: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted. RESULTS: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target. CONCLUSIONS: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.

Value of Conventional Ultrasound-based Scoring System in Distinguishing Adenomatous Polyps From Cholesterol Polyps.

BACKGROUND AND AIM: Ultrasound has increased the detection of gallbladder polyps, but it has limitations in evaluating the nature of gallbladder polyps, especially the maximum size of 1.0 to 1.5 cm. We assessed the value of ultrasound scoring system based on independent predictive parameters in distinguishing adenomatous polyps from cholesterol polyps with the maximum size of 1.0 to 1.5 cm. MATERIALS AND METHODS: We enrolled 163 patients with gallbladder polyps (1.0 to 1.5 cm) who underwent ultrasonography and cholecystectomy. Ultrasound image characteristics were compared between cholesterol polyps and adenomatous polyps in the training cohort from April 2018 to January 2020. An ultrasound scoring system was constructed in the training cohort, and its diagnostic performance was evaluated in the validation cohort from February 2020 to February 2021. RESULTS: Maximum size, height/width ratio, stone or sludge, vascularity, and hyperechoic spot were significantly different between cholesterol polyps and adenomatous polyps in the training cohort ( P <0.05). The independent predictive parameters for adenomatous polyps were lower height/width ratio, presence of vascularity and absence of hyperechoic spot. The total score was as follows: (height/width ratio, <0.9=4, ≥0.9=0) + (vascularity, present=3, absent=0) + (hyperechoic spot, absent=2, present=0). The sensitivity, specificity and accuracy of ultrasound scoring system ≥5 for diagnosis of adenomatous polyps in the validation cohort were 73.33%, 80.49%, and 78.57%, respectively. CONCLUSIONS: The ultrasound scoring system aids in distinguishing adenomatous polyps from cholesterol polyps, and effectively decreasing unnecessary cholecystectomy.

Renal pelvis mucosal artery hemorrhage after percutaneous nephrolithotomy: a rare case report and literature review.

BACKGROUND: Following a percutaneous nephrolithotomy (PCNL) procedure, the most common complications are considered to be intraoperative and postoperative bleeding. Many patients with postoperative bleeding can be treated conservatively, causing the perirenal hematoma to resolve spontaneously. The major causes of severe postoperative bleeding are pseudoaneurysms, arteriovenous fistula, and segmental arterial injury. Typically, the first choice of treatment to manage severe bleeding complications is selective angioembolization (SAE) because of the very high success rate associated with this procedure. CASE PRESENTATION: This clinical case involves a 56-year-old man who underwent dual-channel PCNL treatment after diagnosing a left kidney staghorn stone and urinary tract infection. The operation was successful, with no apparent signs of bleeding. Tests revealed continued decreasing hemoglobin levels following the procedure. After the conservative treatment failed, renal angiography was performed immediately, indicating renal pelvis mucosal artery hemorrhage. In the three hours post-surgery, the SAE still failed to prevent bleeding. Further discussions led to formulating a new surgical plan using a nephroscope to enter the initial channel where hemostasis began. The hemostasis origin was found precisely in the mucosal artery next to the channel during the operation and was successfully controlled. CONCLUSIONS: This case reveals there is poor communication and inadequate discussions about the potential failures of an SAE procedure. Swift clinical decision-making is imperative when dealing with high-level renal trauma to prevent delays in surgery that can threaten the safety of patients.

Post-hepatectomy liver failure prediction and prevention: Development of a nomogram containing postoperative anticoagulants as a risk factor.

INTRODUCTION AND OBJECTIVES: Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients' risk of developing PHLF. PATIENTS AND METHODS: A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index. RESULTS: Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711. CONCLUSION: Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.