Recurrence in isolated distal DVT after anticoagulation: a systematic review and meta-analysis of axial and muscular venous thrombosis.

OBJECTIVE: To identify recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with isolated distal deep vein thrombosis based on its anatomic localization (axial or muscular veins). METHODS: Data were sourced from PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases in the time period up to October 2023. The study followed PRISMA guidelines using a registered protocol (CRD42023443029). Studies reporting recurrent VTE in patients with axial or muscular DVT were included in the analysis. RESULTS: Five studies with a total of 1,403 participants were evaluated. The results showed a pooled odds ratio of 1.12 (95% confidence interval 0.77-1.63) between axial and muscular DVT. Heterogeneity was low (I2 = 0%, p = 0.91) and there was no significant difference in the rate of recurrent VTE between axial and muscular DVT in each subgroup. CONCLUSIONS: Muscular and axial DVT showed comparable recurrent VTE rates after anticoagulation. However, uncertainties regarding the possibility of recurrence affecting the popliteal vein or resulting in pulmonary embolism following muscular DVT anticoagulation persisted. Randomized trials in patients with isolated distal DVT are still needed to clarify its prognosis for different anatomical thrombus locations.

Validation of a pulmonary embolism risk assessment model in gynecological inpatients : Clinical trial: A single-center, retrospective study.

OBJECTIVE: To compare the predictive efficacy of the PADUA and Caprini models for pulmonary embolism (PE) in gynecological inpatients, analyze the risk factors for PE, and validate whether both models can effectively predict mortality rates. METHODS: A total of 355 gynecological inpatients who underwent computed tomography pulmonary angiography (CTPA) were included in the retrospective analysis. The comparative assessment of the predictive capabilities for PE between the PADUA and Caprini was carried out using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify risk factors associated with PE. Additionally, Kaplan-Meier survival analysis plots were generated to validate the predictive efficacy for mortality rates. RESULTS: Among 355 patients, the PADUA and Caprini demonstrated the area under the curve (AUC) values of 0.757 and 0.756, respectively. There was no statistically significant difference in the AUC between the two models (P = 0.9542). Multivariate logistic analysis revealed immobility (P < 0.001), history of venous thromboembolism (VTE) (P = 0.002), thrombophilia (P < 0.001), hormonal treatment (P = 0.022), and obesity (P = 0.019) as independent risk factors for PE. Kaplan-Meier survival analysis demonstrated the reliable predictive efficacy of both the Caprini (P = 0.00051) and PADUA (P = 0.00031) for mortality. ROC for the three- and six-month follow-ups suggested that the Caprini model exhibited superior predictive efficacy for mortality. CONCLUSIONS: The PADUA model can serve as a simple and effective tool for stratifying high-risk gynecological inpatients before undergoing CTPA. The Caprini model demonstrated superior predictive efficacy for mortality rates.

Clinical Guidelines on Compression Therapy in Venous Diseases.

BACKGROUND: In recent years, compression therapy has attracted gradually increasing clinical attention in lower extremity venous diseases. However, basic concepts and clear nomenclature, standard treatment methods, and consistent product standards for pressure equipment are lacking. Therefore, developing clinical guidelines for compression therapy is essential to improving the treatment of venous diseases. METHODS: Our panel generated strong (Grade I), moderate (Grade IIa and IIb), and weak (Grade III) recommendations based on high quality (Class A), moderate quality (Class B), and low quality (Class C) evidence, using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach and the European Society of Cardiology (ESC) grading system. RESULTS: The panels made 30 recommendations from current evidence, focusing on seven fields of lower extremity venous disease (venous thromboembolism, post-thrombotic syndrome, chronic venous insufficiency, varicose veins, hemangioma and vascular malformations, lymphedema, and venous ulcers) and 18 topics. CONCLUSIONS: Of the 30 recommendations made across the 18 topics, 7 were strong (Grade I) and 17 were based on high quality (Class A) evidence, highlighting the need for further research of the use of compression therapy for .

Clinical Outcomes of Drug-Coated Balloon Angioplasty in Peripheral Artery Disease Patients With End-Stage Renal Disease.

PURPOSE: The objective was to determine the effectiveness and safety of paclitaxel-coated balloon angioplasty in hemodialysis patients with diabetic nephropathy (DN). MATERIALS AND METHODS: The outcomes of end-stage renal disease (ESRD) patients with peripheral artery disease (PAD) and treated with drug-coated balloon (DCB) angioplasty were retrospectively evaluated. The effectiveness outcomes were clinical improvement of the Rutherford classification and target lesion revascularization (TLR). Safety outcomes were all-cause mortality and amputation. RESULTS: Ninety-seven patients were treated with DCB angioplasty between December 2018 and December 2020. 87 (63.8±10.1 years) achieved technical success. Most patients had a Rutherford classification of at least grade 4. The mean lesion length was 169.8±73.8 mm, almost all had arterial calcification, and 31.0% had annular calcification. Wounds were present in 73.6% of the target limbs. The mean follow-up in this cohort was 13.4±7.4 months. The wound healing rate was 61.5% at the 12-month follow-up. All-cause mortality during 12 months of follow-up was 35.6%, amputation-free survival was 58.6%, and TLR was observed in 13 (15.3%) patients. At 3 and 12 months of follow-up, the Rutherford grade significantly improved (p<0.001). The Cox proportional hazards model revealed that wounds (hazard ratio [HR]=1.404, p=0.023) and annular calcification (HR=2.076, p=0.031) were independent predictors of amputation-free survival. CONCLUSIONS: Drug-coated balloon angioplasty in ESRD patients was effective and safe over the medium term. Wounds and annular calcification were independent predictors of amputation-free survival. CLINICAL IMPACT: The effectiveness of DCB angioplasty in ESRD patients and the factors affecting major outcome prognosis in this population remain limited. This study contributes valuable insights into the effectiveness and safety of paclitaxel-coated balloon angioplasty for PAD in hemodialysis patients. Medical professionals can now regard DCB angioplasty as a viable treatment. Identifying wound presence and annular calcification as predictors of amputation-free survival equips medical practitioners with a more tailored approach to patient management, potentially resulting in enhanced outcomes and more precise treatment strategies.

Combination of Percutaneous Rotational Thrombectomy and Drug-Coated Balloon for Treatment of Femoropopliteal Artery Nonembolic Occlusion: 12-Month Follow-up.

PURPOSE: To evaluate safety and efficacy of percutaneous mechanical thrombectomy using the Rotarex catheter combined with drug-coated balloon (DCB) in treatment of femoropopliteal artery occlusive disease. MATERIALS AND METHODS: Between January 2016 and February 2018, 81 patients with acute or subacute femoropopliteal artery occlusions were treated with the Rotarex catheter combined with DCB. Lesions were classified according to the onset of symptoms as acutely (< 14 d) or subacutely (14 d to 3 mo) occluded. The mean lesion length was 12.1 cm ± 6.7. The primary endpoint was target lesion patency at 1 year as evaluated by duplex ultrasound (peak systolic velocity ratio < 2.4) and freedom from clinically indicated target lesion revascularization. Amputation rate, major adverse events, and ankle-brachial index at 12 months were evaluated. RESULTS: Technical success rate was 100% (n = 81). Bailout stents were necessary in 14 patients owing to residual stenosis or flow-limiting dissection. Additional thrombolysis was applied in 10 interventions. No major adverse events occurred during hospital stay. There were 9 restenosis cases during the 12-month follow-up period. Primary patency rate was 87.3% (62/71), and freedom from target lesion revascularization rate was 90.1% (64/71). Ankle-brachial index significantly increased from 0.46 ± 0.15 to 0.77 ± 0.14 during follow-up. The amputation rate was 1.4% at 12 months. CONCLUSIONS: These initial data from 2 centers suggest that the combination of the Rotarex catheter and DCB may be safe and effective for treatment of acute or subacute thrombotic femoropopliteal occlusion with superior immediate and midterm results achieved.

Liquid chromatography mass spectrometry-based profiling of phosphatidylcholine and phosphatidylethanolamine in the plasma and liver of acetaminophen-induced liver injured mice.

BACKGROUND: Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice. METHODS: A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver. The expressions of phosphatidylcholine and phosphatidylethanolamine metabolism related genes in liver were detected by quantitative Reverse transcription polymerase chain reaction (qRT-PCR) and Western-blot. RESULTS: Following Acetaminophen treatment, the content of many PC and PE species in plasma increased from 1 h time point, peaked at 3 h or 6 h, and tended to return to baseline at 24 h time point. The relative contents of almost all PC species in liver decreased from 1 h, appeared to be lowest at 6 h, and then return to normality at 24 h, which might be partly explained by the suppression of phospholipases mRNA expressions and the induction of choline kinase (Chka) expression. Inconsistent with PC profile, the relative contents of many PE species in liver increased upon Acetaminophen treatment, which might be caused by the down-regulation of phosphatidylethanolamine N-methyltransferase (Pemt). CONCLUSIONS: Acetaminophen overdose induced dramatic change of many PC and PE species in plasma and liver, which might be caused by damaging hepatocytes and interfering the phospholipid metabolism in Acetaminophen -injured liver.

N-arachidonoylphenolamine alleviates ischaemia/reperfusion-induced cardiomyocyte necroptosis by restoring proteasomal activity.

Necroptosis and apoptosis contribute to the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury and subsequent heart failure. N-arachidonoylphenolamine (AM404) is a paracetamol lipid metabolite that has pleiotropic activity to modulate the endocannabinoid system. However, the protective role of AM404 in modulating I/R-mediated myocardial damage and the underlying mechanism remain largely unknown. A murine I/R model was generated by occlusion of the left anterior descending artery. AM404 (20 mg/kg) was injected intraperitoneally into mice at 2 and 24 h before the I/R operation. Our data revealed that AM404 administration to mice greatly ameliorated I/R-triggered impairment of myocardial performance and reduced infarct area, myocyte apoptosis, oxidative stress and inflammatory response accompanied by the reduction of receptor interacting protein kinase (RIPK)1/3- mixed lineage kinase domain-like (MLKL)-mediated necroptosis and upregulation of the immunosubunits (ß2i and ß5i). In contrast, administration of epoxomicin (a proteasome inhibitor) dramatically abolished AM404-dependent protection against myocardial I/R damage. Mechanistically, AM404 treatment increases ß5i expression, which interacts with Pellino-1 (Peli1), an E3 ligase, to form a complex with RIPK1/3, thereby promoting their degradation, which leads to inhibition of cardiomyocyte necroptosis in the I/R heart. In conclusion, these findings demonstrate that AM404 could prevent cardiac I/R damage and may be a promising drug for the treatment of ischaemic heart disease.

Digital ischemic necrosis in a patient with systematic lupus erythematosus patient after severe acute respiratory syndrome coronavirus 2 infection: a case report.

BACKGROUND: Patients with coronavirus disease 2019 have a high incidence of thrombosis that decreases after recovery. When coronavirus disease 2019 is accompanied by diseases prone to thrombosis, risk of post-infection thrombotic events may increase. CASE PRESENTATION: We report a case of digital ischemic gangrene in a 24-year-old Chinese female with systemic lupus erythematosus after recovery from coronavirus disease 2019. The pathogenesis was related to clinical characteristics of systemic lupus erythematosus, hypercoagulability caused by coronavirus disease 2019, and second-hit due to viral infection. CONCLUSION: Patients with autoimmune diseases should remain alert to autoimmune system disorders induced by severe acute respiratory syndrome coronavirus 2 and other viruses. Treatment for these patients should be strictly standardized, and appropriate anticoagulation methods should be selected to prevent thrombosis.

The mechanosensitive Piezo1 channel exacerbates myocardial ischaemia/reperfusion injury by activating caspase-8-mediated PANoptosis.

PANoptosis is a newly discovered type of cell death characterized by pyroptosis, apoptosis and/or necroptosis and has been implicated in the inflammatory response. Piezo1 is a mechanosensitive ion channel that plays important roles in physiological development and various diseases. However, whether cardiomyocytes undergo PANoptosis during myocardial ischaemia/reperfusion (I/R) injury and the role of Piezo1 in this process remain largely unexplored. In this study, our results revealed that the expression levels of the main components of the PANoptosome, including caspase-8, caspase-3, NLRP3, caspase-1, GSDMD, RIPK1, RIPK3 and MLKL, were significantly upregulated in I/R heart tissues over time, indicating the occurrence of PANoptosis in I/R hearts. Accordingly, Piezo1 expression was significantly upregulated in I/R-injured hearts and hypoxia/reoxygenation (H/R)-treated cardiomyocytes. In contrast, pharmacological inhibition of Piezo1 by the inhibitor GsMTx4 in mice markedly attenuated the I/R-mediated decline in cardiac contractile function and increases in infarct size, apoptosis, oxidative stress and inflammation accompanied by the inhibition of PANoptosis-related mediators in I/R hearts. Consistently, the effects of Piezo1 on calcium influx and PANoptosis were further verified by GsMTx4 and Piezo1 activator Yoda1 in H/R-treated cardiomyocytes in vitro. Moreover, caspase-8 rather than calcium influx was required for H/R-induced PANoptosis in vitro. Mechanistically, Piezo1 interacts with caspase-8, a key initial activator of the PANoptosome complex, which subsequently activates cardiomyocyte PANoptosis, leading to cardiac dysfunction. In summary, these data suggest that Piezo1 is a new cardiac mechanosensor that promotes cardiac I/R injury possibly through the caspase-8-mediated activation of cardiomyocyte PANoptosis and highlight that Piezo1 may represent a new target for treating ischaemic heart disease.

Nomogram for predicting pulmonary embolism in gynecologic inpatients with isolated distal deep venous thrombosis.

OBJECTIVE: To investigate the incidence of isolated distal deep venous thrombosis (IDDVT) concurrent with pulmonary embolism (PE) in gynecologic inpatients, analyze the risk factors for IDDVT with PE, and establish a nomogram model for IDDVT patients with PE. METHODS: A total of 260 patients were diagnosed with IDDVT between December 2017 and November 2020. The incidence of PE in these patients was determined using computed tomography pulmonary angiography. Logistic regression analysis was used to identify the related risk factors. On this basis, nomogram risk prediction models were established. RESULTS: Among 260 patients with IDDVT, 106 (40.8%) had concurrent PE, of whom 74 (28.5%) experienced silent PE. Univariate logistic analysis demonstrated statistical significance for body mass index (BMI; P = 0.044), glucocorticoid therapy (P = 0.009), hypertension (P < 0.001), and diabetes (P < 0.001). Multivariate logistic analysis revealed that these were independent risk factors for IDDVT with PE that retained statistical significance. A nomogram based on these factors was constructed to predict PE in patients with IDDVT. Its receiver operating characteristic (ROC) showed an area under the curve of 0.710 (95% confidence interval 0.642-0.779), with prediction sensitivity of 64.2% and prediction specificity of 76.6%. CONCLUSIONS: In the present study, a high prevalence of PE was found in gynecologic inpatients with IDDVT. Glucocorticoid therapy, hypertension, diabetes, and BMI were independent risk factors for IDDVT patients with PE. Taking these risk factors into account, a nomogram risk prediction model was developed to help facilitate early detection of concurrent PE.

A randomized controlled trial of standard vs customized graduated elastic compression stockings in patients with chronic venous disease.

OBJECTIVE: This study aimed to compare the efficacy of customized graduated elastic compression stockings (c-GECSs) based on lower leg parameter models with standard GECSs (s-GECSs) in patients with chronic venous disease (CVD). METHODS: In this randomized, single-blind, controlled trial, 79 patients with stage C2 or C3 CVD were assigned to one of two groups: c-GECSs or s-GECSs. The primary outcome was change to Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores at months 1, 3, and 6 as compared with baseline. Secondary outcomes included compliance with wearing ECSs, interface pressure at the smallest circumference of the ankle (point B) and the largest circumference of the calf (point C), and calf volume (CV). RESULTS: There were 13 pairs of s-GECS and 2 pairs of c-GECS that showed pressure values higher than the standard at either point B or C. The c-GECSs were significantly superior to s-GECSs in terms of score improvement at all three time points (month 1, 8.47 [95% confidence interval (CI), 7.47-9.45] vs 5.89 [95% CI, 5.00-6.78]; month 3, 9.60 [95% CI, 8.47-10.72] vs 6.72 [95% CI, 5.62-7.83]; month 6, 7.09 [95% CI, 5.93-8.24] vs 3.92 [95% CI, 2.67-5.18]; P < .0001). Besides, at month 1, the mean daily use time of the c-GECS and s-GECS groups was 10.7 and 9.5 hours, respectively (P < .05). Correlation analysis indicated a negative relationship between local high pressure and daily duration in the s-GECS group (rpb = -0.388; n = 38; P < .05). Variances in pressure were greater in the s-GECSs group. The c-GECSs showed advantage in maintaining pressure. Both c-GECSs and s-GECSs effectively reduced CV (mL), with no significant differences between groups (month 1, 90.0 [95% CI, 71.4-108.5] vs 85.0 [95% CI, 65.6-104.2]; month 3, 93.8 [95% CI, 69.7-117.8] vs 85.9 [95% CI, 65.5-106.2]; month 6, 70.8 [95% CI, 46.5-95.2]) vs 60.8 [95% CI, 44.1-77.5]). CONCLUSIONS: The c-GECSs based on individual leg parameter models significantly improved VEINES-QOL scores and provided stable and enduring pressure as compared with s-GECSs for patients with stage C2 or C3 CVD. Although both c-GECSs and s-GECSs effectively reduced CV, the superior fit and comfort of c-GECSs improved patient compliance. Hence, c-GECSs are a viable alternative for patients who have difficulty tolerating s-GECSs.

Development and validation of a graduated compression stockings adherence scale.

OBJECTIVE: Compression therapy with the use of graduated compression stockings (GCSs) is a common treatment strategy for chronic venous disease (CVD). However, there is no uniform and objective standard to assess adherence to the use of GCSs. The aim of this study is to develop and validate a GCS Compliance Scale (GCSAS) to fill gaps in internationally recognized comprehensive scales and provide a useful tool for future research. METHODS: The items included in the GCSAS were based on a review of the literature and open-ended interviews with experts, who screened the initial items using an item-level content validity index. Then, pilot tests were conducted three times with 50 participants. After exclusion of redundant and cross-loading items by exploratory factor analysis, 290 subjects were recruited to evaluate the reliability and validity of the proposed GCSAS. Analyses included internal consistency, test-retest reliability, split-half reliability, construct validity, criterion validity, convergent validity, and discriminant validity. RESULTS: The final GCSAS consisted of 17 items and 5 dimensions. The results of the exploratory factor analysis indicated that the variances of each factor explained were 22.03%, 14.85%, 14.74%, 14.16%, and 13.35%, and all 5 factors explained 79.13% of the variance among the 17 items. The factor loadings of all items were >0.7. Confirmatory factor analysis indicated that the indices were adequate. A significant positive correlation was found between the GCSAS and the Venous Insufficiency Epidemiological and Economic Study - Quality of Life questionnaire scores (r = 0.76, p < 0.001). The Cronbach's alpha coefficient was 0.90, test-retest reliability was 0.81, and split-half reliability was 0.92. CONCLUSIONS: The GCSAS showed good validity and reliability to assess compliance with the use of GCSs among patients with CVD.

Endovascular embolization of visceral artery aneurysm: a retrospective study.

To assess the safety and efficacy of endovascular embolization techniques, we compared the short- to medium-term prognosis of coil embolization for symptomatic visceral aneurysms (SVAA) and asymptomatic visceral aneurysms (ASVAA) to identify risk factors associated with 30-day mortality. Explore the symptom profile and intrinsic associations of SVAA. A retrospective study of 66 consecutive patients at two tertiary care hospitals from 2010 to 2020 compared the short- to mid-term outcomes of 22 symptomatic VAAs and 44 asymptomatic VAAs treated with coil embolization. Univariate and log-rank tests were used to analyze the prognostic impact of SVAA and ASVAA. SVAA group had significantly higher 30-day mortality than ASVAA group (2(9.1%) vs 0, P = 0.042), both patients who died had symptomatic pseudoaneurysms. Perioperative complications such as end-organ ischemia (P = 0.293) and reintervention (P = 1) were similar in both groups. No difference in event-free survival was identified between the two groups (P = 0.900), but we found that the majority of pseudoaneurysms were SVAA (4/5) and that they had a much higher event rate than true aneurysms. In addition, dyslipidemia may be an influential factor in the development of VAA (P = 0.010). Coil embolization is a safe and effective method of treatment for VAA. Most pseudoaneurysms have symptoms such as abdominal pain and bleeding, and in view of their risk, more attention should be paid to symptomatic patients and the nature of the aneurysm should be determined as soon as possible to determine the next stage of treatment.

Three-dimensional laser scanner as a new tool for measuring lower limb volume in patients with chronic venous diseases.

OBJECTIVE: Measurement of lower limb volume in patients with chronic venous disease (CVD) is necessary for assessing severity at the time of diagnosis and evaluating response to therapy administered. Existing methods have some limitations in clinical application and accuracy. The study aimed to investigate the reliability and validity of a three-dimensional laser scanner (3DLS) in measuring the lower limb volume of patients with CVD. METHODS: A total of 30 patients with CVD (mean age, 55.6 ± 8.07 years; mean body mass index, 24.61 ± 1.87) were recruited in a vascular surgery clinic. The lower limb volumes of all participants were measured using the 3DLS and circumferential method (CM). Statistical analysis was conducted to compare the 3DLS and CM. RESULTS: There was a strong correlation between the CM and 3DLS method (r2 = 0.9065). The 3DLS had a high intraoperator and interoperator reliability. A Bland-Altman plot showed satisfactory agreement between the two methods. The 3DLS demonstrated greater bilateral limb differences than CM. CONCLUSIONS: There was satisfactory agreement between the two investigated methods. The 3DLS method was confirmed to be accurate, repeatable, and rapid in measuring the lower limb volume in patients with CVD and is, therefore, suitable for clinical use.

Mesocavoatrial shunt for Budd-Chiari syndrome: a case report with long-term follow-up.

BACKGROUND: A case of mesocavoatrial shunting for the treatment of Budd-Chiari syndrome (BCS) with long-term follow-up is reported. METHODS: A 25-year-old man with stage II BCS was treated with a mesocavoatrial shunt to decompress the portal and IVC hypertension. During the 6-year follow-up, the patient was able to resume work as a salesperson and has since led a normal life. His graft remains patent. CONCLUSION: A mesocavoatrial shunt can simultaneously decompress portal and IVC hypertension and has satisfactory long-term patency. A mesocavoatrial shunt can be used to treat patients with severe BCS who could not be successfully treated with medical therapy and intervention.

Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability.

In our previous study, we reported that sirtuin5 (SIRT5), a member of the NAD+-dependent class III histone deacetylase family, is highly expressed in colorectal cancer (CRC). Herein we show that SIRT5 knockdown impairs the production of ribose-5-phosphate, which is essential for nucleotide synthesis, resulting in continuous and irreparable DNA damage and consequently leading to cell cycle arrest and enhanced apoptosis in CRC cells. These SIRT5 silencing-induced effects can be reversed by nucleoside supplementation. Mechanistically, SIRT5 activates transketolase (TKT), a key enzyme in the non-oxidative pentose phosphate pathway, in a demalonylation-dependent manner. Furthermore, TKT is essential for SIRT5-induced malignant phenotypes of CRC both in vivo and in vitro. Altogether, SIRT5 silencing induces DNA damage in CRC via post-translational modifications and inhibits tumor growth, suggesting that SIRT5 can serve as a promising target for CRC treatment.

Manganese-Catalyzed N-F Bond Activation for Hydroamination and Carboamination of Alkenes.

A visible-light-promoted method for generating amidyl radicals from N-fluorosulfonamides via a manganese-catalyzed N-F bond activation strategy is reported. This protocol employs a simple manganese complex, Mn2(CO)10, as the precatalyst and a cheap silane, (MeO)3SiH, as both the hydrogen-atom donor and the F-atom acceptor, enabling intramolecular/intermolecular hydroaminations of alkenes, two-component carboamination of alkenes, and even three-component carboamination of alkenes. A wide range of valuable aliphatic sulfonamides can be readily prepared using these practical reactions.

Management of complex patients with Budd-Chiari syndrome.

Therapy for patients with Budd-Chiari syndrome is well established. For those with commonly seen localized lesions, percutaneous transluminal angioplasty or stenting is the first-line treatment. Treatment methods for severely ill patients in whom intervention has failed, or those in a poor general condition, are worth exploring. From February 2002 to July 2008, 31 patients were referred to us. Eighteen patients had a failed intervention, 4 had undergone surgery, and 10 had conservative therapy. All had intractable ascites or/and hematemesis. The procedures carried out in this series included mesocavoatrial shunt in 10 patients, radical correction in 9, mesocavojugular shunt in 7 (including 2 mesojugular shunts), mesocaval shunt in 2, cavoatrial shunt in 2 (including a revision of cavoatrial shunt), and cavojugular shunt in 1. Surgical mortality and postoperative complications were both 3.2%. Twenty-eight patients had a mean follow-up of 40 months. Outcome of follow-up was measured as excellent, good, fair, poor, and death (28.6%, 53.6%, 10.7%, 3.6%, and 3.6%, respectively). The total mortality of the group is 6.5%. After appropriate preoperative evaluation and preparation, active and cautious treatment individualized to the underlying disease may help severely ill patients with Budd-Chiari syndrome.

JMJD2B-induced amino acid alterations enhance the survival of colorectal cancer cells under glucose-deprivation via autophagy.

Rationale: Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation. Methods: Non-target metabolic profiling was used to evaluate the roles of JMJD2B in CRC cell metabolism under glucose starvation. The roles of amino acid alterations induced by JMJD2B on CRC cell survival were determined by cell viability, immunoblotting, and clonogenic assays, and flow cytometry. The underlying mechanisms by which JMJD2B affected CRC cell metabolism were assessed using immunofluorescence staining, chromatin immunoprecipitation assays, electron microscopy in CRC cell lines, and using xenograft models. The correlation between JMJD2B and LC3B expression in human CRC specimens was assessed using immunohistochemistry. Results: Profound metabolic reprogramming was detected in JMJD2B knockdown CRC cells under glucose deficiency, especially those involving amino acid metabolites. Silencing of JMJD2B reduced the levels of certain amino acids that were induced by glucose deficiency. Among these amino acids, asparagine (Asn), phenylalanine (Phe), and histidine (His) promoted CRC cell survival under glucose starvation when JMJD2B was knocked down. Mechanistically, downregulation of JMJD2B inhibited autophagy in CRC cells through epigenetic regulation of microtubule associated protein 1 light chain 3 beta (LC3B), and subsequently decreased intracellular amino acid (Asn, Phe, His) levels under glucose deprivation, thus suppressing the survival of CRC cells. Using a nude mouse xenograft model, we verified that inhibiting JMJD2B could decrease the levels of amino acids (Asn, Phe, His). In addition, the inhibitory effects of JMJD2B-knockdown on tumor growth and amino acids level were rescued by overexpression of LC3B. Furthermore, we observed that the high expression of LC3B was more likely detected in tissuses with high expression of JMJD2B (P < 0.001) in 60 human CRC tissues. Conclusion: These results indicated that JMJD2B sustained the intracellular amino acids derived from autophagy in CRC cells upon glucose deficiency, partly through epigenetic regulation of LC3B, thus driving the malignancy of CRC.