Objective:To explore the efficacy and safety of endovascular intervention combined with preoperative laparoscopic exploration in the treatment of patients with acute mesenteric artery ischemia.Methods:This was a prospective cohort study (NCT04686981). The study enrolled 31 patients with acute mesenteric artery ischemia from Oct 1, 2020 to Oct 1, 2022. Among them, 26 patients (84%) were male, with a mean age of (67±13) years and a mean time to onset of (21±8) hours. All patients underwent laparoscopic exploration in the hybrid operating room. If the presence of intestinal necrosis or suspected necrosis was clearly determined, the patient would undergo open surgery (mesenteric artery embolization, intestinal resection and intestinal double stoma) as the treatment by gastrointestinal surgeon. If intestinal necrosis or suspected necrosis was not found by laparoscopy, the patient would undergo endovascular intervention by vascular surgeon. The primary observational endpoints of this study were the proportion of patients who were not dependent on total parenteral nutrition and all-cause mortality within 30 days after operation. The secondary observational endpoints were the rate of mesenteric vascular patency within 30 days and the proportion of interventions that were converted to open surgery.Results:Six patients underwent open surgery and 25 patients underwent endovascular intervention, including 13 cases of thrombus reduction alone, 3 cases of stent implantation during the same period after reduction, and 9 cases of stent implantation alone. Twenty-four patients (77%) were completely weaned from the TPN within 30 days after the procedure, and all-cause mortality was observed in 3 cases (9.7%). The patency rate of the mesenteric artery within 30 days after the procedure was 82.1%. The rate of conversion to open surgery after intervention was 16%.Conclusions:Endovascular intervention combined with preoperative laparoscopic exploration can clarify intestinal ischemia in acute mesenteric patients as early as possible, and individualized treatment strategies for each patient by multidisciplinary care team can potentially improve the prognosis of such patients.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Stroke is the second leading cause of death worldwide,and oxidative stress plays a crucial role.Celastrol exhibits strong antioxidant properties in several diseases;however,whether it can affect oxidation in cerebral ischemic-reperfusion injury(CIRI)remains unclear.This study aimed to determine whether celastrol could reduce oxidative damage during CIRI and to elucidate the underlying mechanisms.Here,we found that celastrol attenuated oxidative injury in CIRI by upregulating nuclear factor E2-related factor 2(Nrf2).Using alkynyl-tagged celastrol and liquid chromatography-tandem mass spectrometry,we showed that celastrol directly bound to neuronally expressed developmentally downregulated 4(Nedd4)and then released Nrf2 from Nedd4 in astrocytes.Nedd4 promoted the degradation of Nrf2 through K48-linked ubiquitination and thus contributed to astrocytic reactive oxygen species production in CIRI,which was significantly blocked by celastrol.Furthermore,by inhibiting oxidative stress and astrocyte activation,celastrol effectively rescued neurons from axon damage and apoptosis.Our study uncovered Nedd4 as a direct target of celastrol,and that celastrol exerts an antioxidative effect on as-trocytes by inhibiting the interaction between Nedd4 and Nrf2 and reducing Nrf2 degradation in CIRI.

Objective:To analyze the effect of endovascular therapy (including balloon dilation, debulking and anti-restenosis technique) for below-the-ankle atherosclerotic lesions in chronic limb threatening ischemic patients.Methods:A retrospective analysis was performed on the clinical data of 465 patients (570 limbs) with below-the-ankle atherosclerosis who were consecutively admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2018 to December 2021. All patients received balloon dilatation below the ankle artery as basic treatment, including 67 patients in debulking subgroup, 82 patients in anti-restenosis subgroup and 11 patients in the triple therapy subgroup. The reocclusion rate, target lesion reintervention rate at 1, 3, 6 and 12 months after surgery were compared; The wound healing rate at 3 months, limb salvage rate at 6 and 12 months and mortality at 12 months in the Global Limb Anatomic Staging System (GLASS) grading groups P0, P1 and P2 were compared.Results:The technical success rate of this group was 76.0%(433 limbs/570 limbs). The follow-up rates of 6 and 12 months after operation were 85.4%(370 limbs/433 limbs) and 75.3%(326 limbs/433 limbs), respectively. The length of treated lesions was (3.6±1.3)cm; The reocclusion rates were 5.5%(23 limbs/420 limbs), 8.2%(33 limbs/403 limbs), 14.9%(55 limbs/370 limbs) and 23.6%(77 limbs/326 limbs) at 1, 3, 6 and 12 months after operation; The reintervention rate of target lesions in 6, 12 months was 7.6%(28 limbs/370 limbs) and 12.0%(39 limbs/326 limbs) respectively; The wound healing rate in groups P0, P1 and P2 within 3 months was 87.3%(192 limbs), 70.5%(62 limbs) and 10.5%(2 limbs) respectively ( P<0.001), the limb salvage rate in 6 months was 96.2%(200 limbs), 84.7%(127 limbs) and 33.3%(4 limbs) respectively ( P<0.001), and the limb salvage rate in 12 months was 78.7%(170 limbs), 54.5%(55 limbs) and 22.2%(2 limbs) respectively ( P<0.001). The mortality was 6.9%(32/465) 12 months after operation. Conclusions:Endovascular therapy below-the-ankle is feasible and has high technical success rate. The constitute integrity of pedal-plantar loop in limb- threatening phase is related to 3-month wound healing rate and limb salvage rate.

The outbreak of coronavirus disease 2019 (COVID-19) was declared a global public health emergency on 31 January 2020. Emergency medicine procedures in Emergency Department should be optimized to cope with the current COVID-19 pandemic by providing subspecialty services, reducing the spread of nosocomial infections, and promoting its capabilities to handle emerging diseases. Thus, the Chinese Society of Emergency Medicine and Wuhan Society of Emergency Medicine drafted this consensus together to address concerns of medical staffs who work in Emergency Department. Based on in-depth review of COVID-19 diagnosis and treatment plans, literatures, as well as management approval, this consensus proposes recommendations for improving the rationalization and efficiency of emergency processes, reducing the risk of nosocomial infections, preventing hospital viral transmission, and ensuring patient safety.

Chronic limb threatening ischemia (CLTI) is a severe condition of peripheral artery disease with high amputation and mortality. Pain and infection cause insufficient nutrient intake and protein loss in CLTI patients,while malnutrition is very prevalent in patients with CLTI and associated with poor prognosis.More and more studies have shown that malnutrition increases the risk of amputation and mortality,delays the time of wound healing.Moderate and severe malnutrition are independent risk factors for amputation and mortality in CLTI patients undergoing surgical or endovascular revascularization.Nutritional screening tools such as Geriatric nutritional risk index,Mini Nutritional Assessment and Controlling nutritional status can help to stratify patients with nutritional risk.Identification of patients with nutritional risk and nutritional intervention can improve the prognosis of CLTI patients.

Chronic limb threatening ischemia (CLTI) is a severe condition of peripheral artery disease with high amputation and mortality. Pain and infection cause insufficient nutrient intake and protein loss in CLTI patients,while malnutrition is very prevalent in patients with CLTI and associated with poor prognosis.More and more studies have shown that malnutrition increases the risk of amputation and mortality,delays the time of wound healing.Moderate and severe malnutrition are independent risk factors for amputation and mortality in CLTI patients undergoing surgical or endovascular revascularization.Nutritional screening tools such as Geriatric nutritional risk index,Mini Nutritional Assessment and Controlling nutritional status can help to stratify patients with nutritional risk.Identification of patients with nutritional risk and nutritional intervention can improve the prognosis of CLTI patients.

In order to explore the effect of extract (SNE) on skin wound healing in mice and its mechanism, hemostasis effect of SNE was measured, the mouse skin wound model was established by full-thickness excision. The morphological changes of the wound were observed after the treatment with SNE and the healing rate was measured. The changes of wound histology were observed by hematoxylin eosin (HE) staining, Masson staining and transmission electron microscope (TEM). The expression of cell factors and related proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that the SNE possessed hemostatic function. SNE could obviously improve the healing rate of wound in mouse and shorten time of scab removal compared with the none-treatment (NT) group ( < 0.05).The pathological histology analysis results showed complete epidermal regeneration, with remarkable capillary and collagen fiber observed in the SNE group. The expression level of tumor necrosis factor-α (TNF -α), interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) in SNE group was significantly lower than that of the NT group on 7 d ( < 0.05). Moreover, compared with the NT group, the gene expressions level of Smad7 was significantly increased and the level of type II TGF-β receptors (TGF-βRII), collagen I (COL1A1) and α-smooth muscle actin (α-SMA) were significantly reduced in the SNE group on 28 d ( < 0.05), but the difference was not statistically significant compared to Yunnanbaiyao group (PC group) ( > 0.05). These results indicated that SNE possessed obvious activity of accelerating wound healing and inhibiting scar formation, and its mechanism was closely related to hemostatic function, regulation of inflammatory factors, collagen deposition, collagen fiber remodeling and intervening TGF-β/Smads signal pathway. Therefore, SNE may have promising clinical applications in skin wound repair and scar inhibition.

Objective To evaluate the experience and early results of radiofrequency ablation (RFA) therapy for varicose veins.Methods In this study 380 extremities of 356 patients undergoing RFA therapy with RFA catheter for varicose veins from Nov 2015 to Sep 2017 in Beijing Tsinghua Changgung Hospital were retrospectively reviewed.Each patient was scheduled to follow up at 1,6 and 12 months respectively.Results Technical success were achieved in all cases.Obliteration rate was 99.0％ in 1 month,97.9％ in 6 months and 97.1％ in 12 months after the RFA therapy.Conclusions RFA therapy for varicose veins is safe and effective and achieves good early result.Intraoperative ultrasound examination and endovascular technique is important for a successful RFA procedure.

OBJECTIVE: To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments. METHODS: We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing. The relapse following the treatments, defined as hematological, cytogenetic and molecular biological recurrences, were analyzed in these patients. RESULTS: Of the 19 patients with CML-T315I, 14 (73.7%) were in CML-CP stage at the initial diagnosis, and 13 (81.2%) were high-risk patients based on the Sokal scores. All the 19 patients were treated with TKI after the initial diagnosis, and during the treatment, 15 (78.9%) patients were found to have additional chromosomal aberrations, and 10 (52.6%) had multiple mutations; 13 (68.4%) of the patients experienced disease progression (accelerated phase/blast crisis) before the detection of T315I mutation, with a median time of 40 months (5-120 months) from the initial diagnosis to the mutation detection. After detection of the mutation, 12 patients were treated with ponatinib and 7 were managed with the conventional chemotherapy regimen, and their overall survival rates at 3 years were 83.3% and 14.2%, respectively ( < 0.001). CONCLUSIONS CML patients resistant to TKI are more likely to have T315I mutations, whose detection rate is significantly higher in the progressive phase than in the chronic phase. These patients often have additional chromosomal aberrations and multiple gene mutations with poor prognoses and a high recurrence rate even after hematopoietic stem cell transplantation. Long-term maintenance therapy with ponatinib may improve the prognosis and prolong the survival time of the patients.
Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; Humans ; Imidazoles ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mutation ; Pyridazines ; Retrospective Studies